Pancreatic duct stenting for the duration of ERCP only does not prevent pancreatitis after accidental pancreatic duct cannulation: a prospective randomized trial

Background

Pancreatic duct stent placement during endoscopic retrograde cholangiopancreatography (ERCP) has been recommended in patients at risk for post-ERCP pancreatitis. However, the optimal duration of stent placement remains an open question. Our aim was to compare the efficacy of pancreatic stenting for the duration of ERCP only with spontaneous dislodgment/deferred endoscopic removal in preventing post-ERCP pancreatitis after accidental wire-guided pancreatic duct cannulation.

Methods

All patients in whom accidental wire-guided pancreatic duct cannulation had occurred during ERCP underwent immediate 5-Fr unflanged pigtail pancreatic duct stenting before attempting any other endoscopic maneuver. At the end of the ERCP, patients were randomly assigned to immediate stent removal (group A) or to leaving the stent in place (group B). Assessment of post-ERCP pancreatitis was blind.

Results

Post-ERCP pancreatitis occurred in 6/21 (29 %) patients in group A and in 0/19 patients in group B (P = 0.021); the two groups were well matched for their baseline characteristics. Post-ERCP pancreatitis was mild in two patients, moderate in two patients, and severe in two patients. Stents dislodged spontaneously in 14/19 (74 %) patients within 24–96 h; uneventful endoscopic removal was carried out after 96 h in 5 cases. Proximal stent migration did not occur in any case.

Conclusions

Pancreatic duct stent placement for the duration of ERCP only does not prevent post-ERCP pancreatitis. Pancreatic stents should be left in place until spontaneous dislodgment occurs or endoscopic removal is deemed timely. 5-Fr unflanged pigtail stents remain in place for a period sufficient to prevent post-ERCP pancreatitis and do not migrate proximally.     

A comparative study of 10-Fr vs. 7-Fr straight plastic stents in the treatment of postcholecystectomy bile leak

Background Biliary decompression is a key factor in the treatment of postcholecystectomy bile leak. However, the optimal size of the stent introduced by therapeutic endoscopic retrograde cholangiopancreatography (ERCP) is yet to be determined. The aim of the study was to compare the effectiveness of two straight plastic stents with different sizes (10-Fr and 7-Fr) in the treatment of postcholecystectomy bile leak. Methods Between January 2003 and August 2006, 63 patients underwent therapeutic ERCP for postcholecystectomy bile leak. After visualization of the bile duct injury, endoscopic sphincterotomy was performed and the patients were randomized to receive either a 7-Fr (31 subjects, group A) or a 10-Fr (32 subjects, group B) straight plastic stent for four weeks. The success of the endoscopic treatment was determined by the elimination of the symptoms and the removal of the drain without any adverse outcomes. Results The endoscopic intervention was successful in 29 patients of group A (93.54%) and in 31 patients of group B (96.87%). In the remaining two patients of group A, the 7-Fr stent was substituted by a 10-Fr stent after 7 days because the leak remained unaffected, resulting in healing of the leaks. Surgery was required in the remaining one patient of group B. Eight patients developed post-ERCP pancreatitis (5 mild, 2 moderate, 1 severe), which was treated conservatively. Conclusions This trial suggests that the stent size does not affect the outcome of the endoscopic intervention in postcholecystectomy bile leaks due to minor biliary tract injury; however, larger cohorts are required to confirm the optimal stent size in bile leaks due to major bile duct injury.     

Post-ERCP pancreatitis: Reduction by routine antibiotics

Cholangitis and pancreatitis are severe complications of endoscopic retrograde cholangiopancreatography (ERCP). Antibiotics have been considered important in preventing cholangitis, especially in those with jaundice. Some have suggested that bacteria may play a role in the induction of post-ERCP pancreatitis. It is not clear, however, whether the incidence of post-ERCP pancreatitis could be reduced by antibiotic prophylaxis, as is the case with septic complications. In this prospective study, a total of 321 consecutive patients were randomized to the following two groups: (1) a prophylaxis group (n = 161) that was given 2 g of cephtazidime intravenously 30 minutes before ERCP, and (2) a control group (n = 160) that received no antibiotics. All patients admitted to the hospital for ERCP who had not taken any antibiotics during the preceding week were included. Patients who were allergic to cephalosporins, patients with immune deficiency or any other condition requiring antibiotic prophylaxis, patients with clinical jaundice, and pregnant patients were excluded. In the final analysis six patients were excluded because of a diagnosis of bile duct obstruction but with unsuccessful biliary drainage that required immediate antibiotic treatment. The diagnosis of cholangitis was based on a rising fever, an increase in the C-reactive protein (CRP) level, and increases in leukocyte count and liver function values, which were associated with bacteremia in some. The diagnosis of acute pancreatitis was based on clinical findings, and increases in the serum amylase level (>900 IU/L), CRP level, and leukocyte count with no increase in liver chemical values. The control group had significantly more patients with post-ERCP pancreatitis (15 of 160 in the prophylaxis group vs. 4 of 155 in the control group; P = 0.009) and cholangitis (7 of 160 vs. 0 of 155; P = 0.009) compared to the prophylaxis group. Nine patients in the prophylaxis group (6%) and 15 patients in the control group (9%) had remarkably increased serum amylase levels (>900 III/L) after ERCP, but clinical signs of acute pancreatitis with leukocytosis, CRF’ reaction, and pain developed in four of nine patients in the prophylaxis group compared to 15 of 15 patients with hyperamylasemia in the control group (P = 0.003). In a multivariate analysis, the lack of antibiotic prophylaxis (odds ratio 6.63, P = 0.03) and sphincterotomy (odds ratio 5.60, P = 0.05) were independent risk factors for the development of post-ERCP pancreatitis. We conclude that antibiotic prophylaxis effectively decreases the risk of pancreatitis, in addition to cholangitis after ERCP, and can thus be routinely recommended prior to ERCP These results suggest that bacteria could play a role in the pathogenesis of post-ERCP pancreatitis.     

鼻胆管引流对于ERCP术后并发症的防治

目的探讨内镜下鼻胆管引流术预防和治疗ERCP术后胰腺炎、胆道感染、穿孔等并发症的效果。方法回顾分析2003年5月至2005年5月间868例ERCP患者的临床资料,其中657例于内镜治疗后行置鼻胆管引流,211例患者未行鼻胆管引流。在行鼻胆管引流的患者中,胆道结石为354例,胆道恶性梗阻为128例,胆总管扩张为56例,胆总管囊肿为17例,缩窄性乳头炎为34例,ERCP未见明显异常68例;未行鼻胆管或内支架引流的患者中,胆总管结石116例,胆总管扩张51例,胆总管囊肿3例,缩窄性乳头炎11例,ERCP未见明显异常30例。结果两组术后急性胰腺炎发生率分别为1.4%和3.8%(P>0.05),但引流组均为轻症胰腺炎,而非引流组50%为重症胰腺炎。急性胆管炎的发生率分别为0.5%和2%(P<0.05),而且非引流组中40%出现AOSC,需手术治疗。胰管显影率分别为13%和14%(P>0.05);穿孔各2例(0.3%vs0.9%),其中未行鼻胆管引流组中1例经手术后痊愈,其余均经非手术治疗痊愈。结论内镜下鼻胆管引流能有效预防和治疗部分ERCP并发症。     

奥曲肽联合泮托拉唑预防内镜逆行胰胆管造影术后胰腺炎

目的：探讨内镜逆行胰胆管造影（ERCP）术后胰腺炎的预防措施。 方法：将2010年7月—2012年11月间行ERCP术后的患者100例,随机分为观察组和对照组,每组各50例患者。观察组术后给予联合应用生长抑素（奥曲肽0.1 mg/8 h皮下注射连用24 h）和质子泵抑制剂作预防治疗（泮托拉唑40 mg/d静脉滴注连用2 d）,对照组给予生理盐水静脉滴注。比较两组患者ERCP术后3,12,24 h的血清淀粉酶情况,及胰腺炎的发生情况。 结果：两组一般资料比较具有可比性;在术后3,12,24 h各时间点比较,观察组血清淀粉酶水平均明显低于对照组（均P<0.05）;观察组术后12,24 h高淀粉酶血症发生率及术后急性胰腺炎明显均低于对照组（18% vs. 42%;8% vs. 22%;2% vs. 16%）（均P<0.05）。 结论：联合应用生长抑素和质子泵抑制剂可减少ERCP术后高淀粉酶血症与胰腺炎的发生率,是一种安全且有效的ERCP术后胰腺炎预防措施。     

《日本急性胰腺炎治疗指南（2015）》评介

《日本急性胰腺炎治疗指南》发表于2006年,2010年进行了修订。结合2013年对亚特拉大分类重新评价的国际共识,2015年日本再次对其指南进行了更新修订。《日本急性胰腺炎治疗指南（2015）》针对17项与诊治相关的临床领域,以循证医学为指导原则,设计了39个临床具体问题及43条推荐意见。针对抗生素的预防性应用、胰管支架留置在预防内镜逆行胰胆管造影（ERCP）后胰腺炎中的作用、非甾体抗炎药物在预防ERCP后胰腺炎中的作用、腹腔灌洗对改善病人预后的作用等4个课题重新进行了荟萃分析。《日本急性胰腺炎治疗指南（2015）》较为全面地总结概括了急性胰腺炎临床诊治的指导原则,反映了急性胰腺炎治疗现状与进展,值得参考、学习和借鉴。     

Risk of pancreatitis following endoscopically placed large-bore plastic biliary stents with and without biliary sphincterotomy for management of postoperative bile leaks

BACKGROUND: Endoscopic transpapillary biliary stent placement is effective for closure of postoperative bile leaks. Large-bore stents (10 French) may transiently obstruct the adjacent pancreatic duct orifice causing acute pancreatitis. Endoscopic biliary sphincterotomy may reduce this risk, but it introduces separate risks of bleeding and perforation. The objective of this study was to compare complications after large-bore biliary stent placement (10 Fr) with and without sphincterotomy in patients with bile leaks. METHODS: The institutional endoscopy database was queried to identify patients who had undergone endoscopic retrograde cholangiopancreatogrpahy (ERCP) for bile leak between March 1996 and August 2006. Procedural reports were reviewed for evidence of biliary sphincterotomy, cholangiographic and pancreatographic findings, transpapillary stent placement, and procedural complications. Patients with prior biliary sphincterotomy, choledochoenteric anastomosis, placement of multiple biliary stents and expandable metal biliary stents, biliary stents smaller than 10 Fr, and patients in whom a stent was not placed were excluded. The chi-square test was used for categorical variables. Probability 相似文献   

Rescue ERCP and insertion of a small-caliber pancreatic stent to prevent the evolution of severe post-ERCP pancreatitis: a case-controlled series

Introduction  Recently prophylactic placement of a trans-sphincteric pancreatic stent has successfully been applied to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. Rescue ERCP and emergency application of small-caliber pancreatic stents during the early course of post-ERCP pancreatitis as a possible endoscopic therapy has not been reported yet. Methods  All patients who underwent ERCP were hospitalized for at least 24 h, with routine laboratory testing of amylase levels. Out of 1,225 ERCPs, evolution of severe post-ERCP pancreatitis was anticipated in six consecutive patients, based on severe pancreatic pain attack, more than tenfold elevation of serum amylase levels at 8 and 24 h, and moderate rise of white blood cell (WBC) and C-reactive protein (CRP) levels. Rescue ERCP and emergency application of small-caliber (4-5F, 4-cm, Geenen stent) pancreatic stents were successfully performed in all patients within 8–20 h after the initial ERCP. Results  Moderate to severe papillary oedema was observed in all patients during the rescue ERCP. Pancreatic pain was promptly reduced after the rescue pancreatic drainage procedure and completely diminished within 24 h after pancreatic stenting. Serum amylase levels were exponentially reduced and normalized within 72 h in all patients; no pancreatic necrosis or any other late complications were observed. Pancreatic stents could be safely removed a few days later. Conclusion  Rescue pancreatic stenting with small-caliber prophylactic pancreatic stents seems to be a safe and effective procedure that might be feasible to stop the evolution of severe post-ERCP pancreatitis, but prospective controlled studies are clearly demanded to support this innovative approach.     

Early treatment with antibiotics reduces the need for surgery in acute necrotizing pancreatitis—a single-center randomized study

Pancreatic infection is the main indication for surgery and the principal determinant of prognosis in acute necrotizing pancreatitis. Previous studies on the effects of antibiotics have not, however, uniformly demonstrated any reduction in the need for surgery or any decrease in mortality among these patients, although the incidence of pancreatic infections was significantly reduced. This single-center randomized study was designed to compare early vs. delayed imipenem treatment for acute necrotizing pancreatitis. Ninety patients with acute necrotizing pancreatitis (C-reactive protein >150 mg/L, necrosis on CT) were randomized within 48 hours either to a group receiving imipenem (1.0 g plus cilastatin intravenously 3 times a day) or a control group. Not included were those who had been started on antibiotics at the referring clinic, those who were taken directly to the intensive care unit for multiorgan failure, and those who refused antibiotics or might have had adverse reactions. Thirty-two patients were excluded because they were over 70 years of age (not potentionally operable) or for any study violation. There were 25 patients in the imipenem group and 33 patients in the control group. The main end point was the indication for necrosectomy due to infection (i.e., after the initial increase and decrease, there was a second continuous increase in temperature, white blood cell count [>30%] and C-reactive protein [>30%], with other infections ruled out, or bacteria were found on Gram stain of the pancreatic fine-needle aspirate). In the control group, imipenem was started when the operative indication was fulfilled. Conservative treatment was continued for at least 5 days before necrosectomy. The study groups did not differ from each other with regard to sex distribution, patient age, etiology, C-reactive protein concentration, and extent of pancreatic necrosis on CT. Two (8%) of 25 patients in the imipenem group compared to 14 (42%) of 33 in the control group fulfilled the operative indications (P = 0.003). Nine patients in the control group responded to delayed antibiotics but five had to undergo surgery. Of those receiving antibiotics, 2 (8%) of 25 in the early antibiotic (imipenem) group needed surgery compared to 5 (36%) of 14 in the delayed antibiotic (control) group (P = 0.04). Two (8%) of 25 patients in the imipenem group and 5(15%) of 13 patients in the control group died (P = NS [no significant difference]). Seven (28%) of 25 in the imipenem group and 25 (76%) of 33 in the control group had major organ complications (P = 0.0003). Based on the preceding criteria, early imipenem-cilastatin therapy appears to significantly reduce the need for surgery and the overall number of major organ complications in acute necrotizing pancreatitis, and reduces by half the mortality rate; this is not, however, statistically significant in a series of this size. Presented at the Forty-First Annual Meeting of The Society for Surgery of the Alimentary Tract, San Diego, Calif., May 21–24, 2000.     

急性胰腺炎复发病例的临床研究

目的：研究急性胰腺炎复发的基本病因及影像学特点。方法：回顾性分析５６例急性胰腺炎复发（复发组）及６１例初发胰腺炎（对照组）病人的基本病因、Ｂ超、ＣＴ和ＥＲＣＰ检查的变化规律以探讨其病因。结果：复发组病人胆石症发病率为６０．７％,显著高于对照组的３１．１％（Ｐ＜０．０１）;对照组发病原因不明者达５０．８％,显著高于复发组（Ｐ＜０．０１）。复发组病人中放射痛、腹肌紧张和黄疸的发生率分别为４８．２％、２１．４％和１６．１％,显著高于对照组（Ｐ＜０．０５）。Ｂ超检查发现,复发组胰腺回声粗强者达３５．７％,胰管扩张者达１９．６％,均显著高于对照组;胆囊炎、胆结石和胆总管扩张的发病率也显著高于对照组。ＣＴ示复发组胰腺假性囊肿、肿大、坏死的发生率高于对照组,但无统计学意义。ＥＲＣＰ示复发组胆总管结石、扩张的发生率显著高于对照组（Ｐ＜０．０１）;主胰管结石、扩张、狭窄及乳头部病变发生率也明显增多。结论：胆囊炎、胆囊结石、胆总管结石等疾病可能是急性胰腺炎复发的主要病因。其他还有一部分病人是慢性胰腺炎的急性发作。     

The Effects of Cefephim, G-CSF, and Sucralfate on Bacterial Translocation in Experimentally Induced Acute Pancreatitis

The preventive effects of granulocyte colony-stimulating factor, cefephim, and sucralfate on bacterial translocation in experimentally induced acute pancreatitis were investigated. Forty male Wistar albino rats were used in this study. For each rat, the pancreatobiliary ductus was ligated and hence acute pancreatitis was induced. In the control group, no further procedure was performed. Meanwhile, cefephim as an antibiotic, filgrastim, which is a colony-stimulating factor, and sucralfate were given to the other groups at the specified doses. To inhibit bacterial translocation by preserving the bowel barrier, sucralfate, which is known to have a cytoprotective effect on the gastrointestinal system, was used in high doses. Cefephim 30 mg/kg per day (intramuscularly) in group II, filgrastim 10 mg/kg per day (subcutaneously) in group III, and sucralfate 50 mg/kg per day by 8-F feeding tube gavage into the stomach in group IV were given. The number of bacteria translocated into the mesenteric lymph nodes, pancreas, liver, and spleen in the control group significantly increased in comparison with the other groups (P < 0.05). The average number of leukocytes (per mm³) in the control group was significantly higher than that of other groups (P < 0.0001). Regarding the average serum amylase levels, the values of all groups clearly decreased in comparison with the control group (P < 0.0001). Although in the cefephim, filgrastim, and sucralfate groups, (+) pancreatitis was generally seen, in the control group (+++) pancreatitis was detected. Bacterial translocation to the mesenteric lymph nodes and pancreas was partially prevented by filgrastim and sucralfate, and was completely prevented by cefephim. We conclude that in the management of acute pancreatitis, the use of the prophylactic antibiotics, sucralfate and filgrastim, may be advantageous. Received: July 2, 1999 / Accepted: September 26, 2000     

胰管支架引流术在急性胆源性胰腺炎治疗中的应用价值

背景与目的:急性胆源性胰腺炎(ABP)是临床上一种常见疾病,其最常见的病因为胆总管结石.目前主流观点认为,对于发病早期的ABP患者应尽早行内镜下逆行性胰胆管造影(ERCP)、内镜下十二指肠乳头括约肌切开术(EST)联合鼻胆管引流术(ENBD).然而在以上治疗过程中是否应该同期行胰管支架引流术的争议较多.针对这一问题,本...     

Use of the laparoscopic–endoscopic approach, the so-called “rendezvous” technique, in cholecystocholedocholithiasis

Background Several studies have shown the efficacy and effectiveness of the combined endoscopic–laparoscopic “rendezvous” technique for treatment of gallbladder and bile duct stones without complications, particularly pancreatitis. The so-called rendezvous technique consists of laparoscopic cholecystectomy standards with intraoperative cholangiography followed by endoscopic sphincterotomy (EST). The sphincterotome is driven across the papilla through a guidewire inserted by the transcystic route. This method allows easier and faster cannulation, thus avoiding papillary edema and pancreatic trauma. The aim of this study was to evaluate whether this method is effective in eliminating ductal stones and to verify whether the risk of postprocedure pancreatitis is diminished. Methods From January 2002 to September 2004, we enrolled 256 patients with cholecystocholedolithiasis detected by transabdominal ultrasound and magnetic resonance cholangiopancreatography. One hundred and twenty of these had one or more patient-related risk factors for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis, so they were randomized into two groups of 60 patients. In group A, the patients were treated in a single step with videolaparoscopic cholecystectomy, intraoperative cholangiography, and EST during the surgical procedure with the rendezvous technique. In group B, preoperative ERCP and EST were performed by using a traditional method of bile duct cannulation. Results No cases of post-ERCP pancreatitis were observed in group A, whereas six cases of acute post-ERCP pancreatitis occurred in group B (five mild and one moderate) (p = 0.0274). No procedure-related mortality was recorded. Conclusion In cholecysthocholedocholithiasis, the combined laparoscopic–endoscopic approach prevents post-ERCP pancreatitis in cases with patient-related risk factors for this complication.     

Effect of early antibiotic prophylaxis with ertapenem and meropenem in experimental acute pancreatitis in rats

Background  The clinical course in acute necrotizing pancreatitis is mainly influenced by bacterial infection of pancreatic and peripancreatic necrosis. The effect of two antibiotic treatments for early prophylaxis was studied in the taurocholate model of necrotizing pancreatitis in the rat. Methods  Sixty male Sprague-Dawley rats were divided into three pancreatitis groups (15 animals each) and a sham-operated group (15 animals, control group). Pancreatitis was induced by intraductal infusion of 3% taurocholate under sterile conditions. Animals were placed on one of two different antibiotic regimens (15 mg/kg ertapenem or 20 mg/kg meropenem, one shot) after the induction of pancreatitis or received no antibiotics (control). All animals were sacrificed after 24 h to study pancreatic and extrapancreatic infection. Results  Early antibiotic prophylaxis with either erapenam or meropenem significantly decreased pancreatic infection from 12/15 (control group) to 4/15 (ertapenem antibiotic group) and 3/15 (meropenem antibiotic group) (P < 0.05). Conclusions  In our animal model of necrotizing pancreatitis, early antibiotic prophylaxis with ertapenem and meropenem reduced bacterial infection of the pancreas. The efficacy of early antibiotic prophylaxis with ertapenem in the clinical setting should be subject to further research.     

Effects of nafamostat mesilate, somatostatin, and glucagon on caerulein-induced acute pancreatitis in rats

The inhibitory effects of somatostatin (SMS) and glucagon (Gn) on acute pancreatitis were evaluated in an experimental acute pancreatitis model in male Wistar rats. The effects of these agents were compared with those of nafamostat mesilate (NM). The acute pancreatitis was induced by four serial subcutaneous injections of caerulein. The rats were divided into four groups. The first group (n=28) received SMS daily, the second group (n=28) received Gn daily, and the third group (n=28) received NM daily after the first injection of caerulein. The fourth group (n=42) received caerulein alone and served as the control group. Animals were sacrificed 4, 6, 8, 12, and 24 h, and 3 and 7 days after the first administration of caerulein and the degree of severity of the acute pancreatitis was evaluated by serial morphological and histological examinations of pancreatic tissues, as well as in terms of the serum concentrations of amylase and lipase. The characteristic findings of acute pancreatitis in the animals of all groups treated with SMS, Gn, or NM were markedly attenuated at all time points after the treatments compared with findings in the controls (caerulein alone) in terms of wet weight of pancreas, serum concentrations of amylase and lipase, formation of intracellular vacuoles in acinar cells, interstitial edema, and infiltration of an inflammatory cell component. The inhibitory effects of SMS, Gn, and NM on acute pancreatitis were similar at the doses used. These results suggest that SMS and Gn are as useful as NM, they may be of value for the treatment of acute pancreatitis.     

Pancreatic sphincterotomy versus needle knife precut in difficult biliary cannulation

Background  In endoscopic retrograde cholangiopancreaticography (ERCP) difficult cannulation is an independent risk factor for complications. Methods  Altogether 6,209 ERCPs were performed in Helsinki University Central Hospital in the period 1996–2006. In 558 cases (9%) without a previous sphincterotomy, direct access into the biliary duct could not be achieved. In this group access was attempted by first performing a pancreatic sphincterotomy in 351 difficult cannulation cases (63%). A needle knife precut without a pancreatic sphincterotomy was performed in 178 cases (32%). All the necessary clinical and laboratory information was available for 262 of the 351 patients who had undergone a pancreatic sphincterotomy and for 157 of the 178 patients who had been subjected to needle knife precutting, and these data were further evaluated in this study. Results  The pancreatic sphincterotomy technique was successful in 255 cases (97.3%). Post-ERCP pancreatitis developed in 8.8% of the pancreatic sphincterotomy group. In 147 patients, biliary cannulation was successful following a pancreatic sphincterotomy, and the post-ERCP pancreatitis rate for those patients was 9.3%. In 108 patients, a needle knife papillotomy, in addition to a pancreatic sphincterotomy, was necessary and resulted in a post-ERCP pancreatitis rate of 8.2%. In the needle knife precut group only, post-ERCP pancreatitis developed in 5.1% of cases. Biliary cannulation succeeded less frequently following needle knife precutting than following the pancreatic sphincterotomy technique (71.3% versus 97.3%, p < 0.001). There was no significant difference in the post-ERCP pancreatitis rate between the precut and pancreatic sphincterotomy techniques (p = 0.16). Conclusions  In difficult cannulation, a pancreatic sphincterotomy to achieve deep biliary duct cannulation can be performed with a high success rate (failure rate less than 3%). The corresponding success rate using the needle knife precut technique is 71%. In both methods the risk for post-ERCP pancreatitis is comparable to that of a standard biliary sphincterotomy.     

Low-dose heparin for the prevention of post-ERCP pancreatitis: a randomized placebo-controlled trial

Background  As suggested by observational and animal studies, heparin has antiinflammatory effects that could prevent acute post–endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. Low-molecular-weight heparin did not reduce the incidence of post-ERCP pancreatitis in a controlled study. The current study aimed to determine whether prophylactic administration of low-dose unfractionated heparin, which has potentially more antiinflammatory capability, can prevent acute post-ERCP pancreatitis. Methods  Patients scheduled for ERCP in the authors’ department were randomized to receive unfractionated heparin (5,000 IU) or placebo (saline solution 0.5 ml) administered subcutaneously 20 to 30 min before the ERCP. Patients who had undergone endoscopic sphincterotomy in the past were excluded from the study. Post-ERCP pancreatitis was defined according to criteria established by Cotton: abdominal pain combined with a threefold elevation of blood amylase 24 h after the ERCP. Results  The study enrolled 106 patients. One patient was excluded from the analysis due to inaccessible papilla of Vater, leaving 51 patients in the heparin group and 54 in the placebo group, for a total of 105 patients (62 women and 43 men) with a mean age of 64.6 years. The rate of post-ERCP pancreatitis was not different between the groups (heparin, 4 patients, 7.8%; placebo, 4 patients, 7.4%). Two patients in each group experienced mild bleeding. Conclusions  The study did not demonstrate a significant effect of low-dose unfractionated heparin in the prevention of post-ERCP pancreatitis. A multicenter trial with a larger number of patients is needed to demonstrate a benefit from this drug.     

The effects of contrast agent and intraductal pressure changes on the development of pancreatitis in an ERCP model in rats

Objective Although there are various experimental pancreatic models in animals, only a few studies have evaluated how intraductal pressure and contrast agent affect the development of pancreatitis after endoscopic retrograde cholangiopancreatograpy (ERCP). Materials and methods The rats were randomly divided into seven groups (n = 8/group). The rats in all groups underwent laparotomy and their biliopancreatic ducts were cannulated transduodenally using a 24G catheter. In the control group, group 1, the biliopancreatic ducts of the rats were not infused with any fluid. The biliopancreatic ducts of the rats in groups 2, 3, and 4 were infused with 0.5 ml isotonic NaCl solution at 10, 2, and 50 mmHg, respectively. Groups 5, 6, and 7 were given 0.5 ml of 50% diluted contrast agent at 10, 25, and 50 mmHg, respectively. The serum amylase, aspartate aminotransferase (AST), lactic dehydrogenase (LDH), and C-reactive protein (CRP) were measured 24 h after the procedure. Pancreatic tissue was also evaluated histopathologically. Results Pancreatitis due to the contrast agent was noted when comparing the low pressure isotonic NaCl group and the low pressure contrast group (p < 0.05). Based on serum amylase and CRP values, there was a positive correlation between the severity and frequency of acute pancreatitis and pressure (p < 0.01). AST and LDH levels increased in all of the groups that underwent the procedure; however, no correlation was detected with increasing pressure or with the use of contrast agent (p > 0.05). Both pancreatic edema and the inflammatory cell infiltration score were elevated in isotonic NaCl and contrast group (p < 0.05); however, necrosis was not significantly changed (p > 0.05). Conclusion The results of this study suggest that the main mechanism for preventing pancreatitis after ERCP is to minimize trauma to the pancreatic canal, to cannulate the pancreas only when it is necessary, and to give contrast agent under low pressure when it is needed.     

Effects of heparin in experimental models of acute pancreatitis and post-ERCP pancreatitis

BACKGROUND: Acute pancreatitis (AP) is a complication of diagnostic or therapeutic endoscopic retrograde cholangiopancreatography (ERCP). In a recent clinical trial, a decreased rate of post-ERCP pancreatitis was shown after prophylactic heparin treatment. The aim of this study was to evaluate the effects of prophylactic heparin application in various experimental models of AP and pancreatic duct obstruction and to assess the underlying mechanisms. METHODS: In various experimental models, pancreatic injury of graded severity was induced in Wistar rats: (1) mild pancreatitis by IV cerulein infusion over 6 hours; (2) severe pancreatitis by infusion of glycodeoxycholic acid into the pancreatic duct plus IV cerulein application over 6 hours. The clinical ERCP situation was imitated in groups (3) obstruction of the pancreatic duct and (4) infusion of contrast medium into the pancreatic duct plus obstruction. In every group the animals received either no heparin (n=six per group) or continuous IV heparin (n=six per group) starting before pancreatic injury. Histologic changes, amylase, and lipase in plasma were evaluated 12 hours after induction of pancreatic injury. Additional animals were treated to investigate pancreatic microcirculation by intravital microscopy (n=six per group). RESULTS: In groups 1, 3, and 4 (mild AP/duct obstruction/duct obstruction plus contrast medium), IV heparin-treated animals showed reduced edema, inflammation, and peak amylase values compared with the corresponding non-heparin-treated animals (P<.05). Moreover, mean erythrocyte velocity was significantly higher and leukocyte-endothelium interaction was reduced in these groups after prophylactic administration of heparin. In contrast, group 2 (severe AP) did not show any difference between control animals and animals that received heparin as assessed by histology and intravital microscopy. CONCLUSIONS: Prophylactic systemic application of heparin provides a protective effect in mild AP and in experimental post-ERCP pancreatitis. The mechanism of the protective effects of heparin seems to be the reduction of leukocyte-endothelium interaction and the normalization of pancreatic microcirculation.     

Minor papilla sphincterotomy for pancreatitis due to pancreas divisum

Background: Pancreas divisum (PD) is the commonest congenital pancreatic abnormality and is implicated as a cause of acute recurrent pancreatitis (ARP). We report our experience in minor papilla sphincterotomy (MPS) for this condition. Studies published at present have not examined MPS as the primary treatment method in a homogenous (i.e. only those with ARP) patient group. Methods: Patients with PD and ARP were identified from an endoscopic database. Treatment protocol consisted of minor papilla guidewire cannulation and sphincterotomy with either sphincterotome over the wire or needle knife over pancreatic stent. A 5‐Fr stent was placed for 1 week. Adjunctive therapy was carried out as required. Follow‐up data was collected by interview with the patient and referring doctors and review of the medical record. Results: Twenty‐one patients underwent MPS for PD and ARP (median age = 33 years, range 9–77 years, men = 14). Median number of procedures to achieve cannulation and MPS was 1 (range 1–3). Complications encountered were pancreatitis (n = 2) and pain (n = 3). MPS restenosis occurred in 2. Adjuvant therapy was required in 14: stricture dilatation (n = 9), stone extraction (n = 7) and extracorporeal shock‐wave lithotripsy (n = 6). Complete stone clearance was achieved in 7/7. Median follow up was 38 months (range 4–67 months). Median total number of pancreatitis episodes and hospitalizations pre‐MPS were 4 and 2, respectively (range 1–20 and 0–5, respectively). Post‐MPS these were reduced to 0 and 0, respectively (range 0–8 and 0–4; P = 0.0007 and P = 0.0003), with complete abolition of episodes in 13 patients. Conclusion: MPS in association with other endoscopic therapies imparts a significant clinical benefit to patients with ARP and PD. Complete clinical resolution occurs in the majority. Treatment is safe, and the response is durable.