Martin L. Freeman

Practice guidelines in acute pancreatitis.

Guidelines for clinical practice are intended to suggest preferable approaches to particular medical problems as established by interpretation and collation of scientifically valid research, derived from extensive review of published literature. When data are not available that will withstand objective scrutiny, a recommendation may be made based on a consensus of experts. Guidelines are intended to apply to the clinical situation for all physicians without regard to specialty. Guidelines are intended to be flexible, not necessarily indicating the only acceptable approach, and should be distinguished from standards of care that are inflexible and rarely violated. Given the wide range of choices in any health care problem, the physician should select the course best suited to the individual patient and the clinical situation presented. These guidelines are developed under the auspices of the American College of Gastroenterology and its practice parameters committee. These guidelines are also approved by the governing boards of the American Gastroenterological Association, American Society for Gastrointestinal Endoscopy, and American Association for the Study of Liver Diseases. Expert opinion is solicited from the outset for the document. Guidelines are reviewed in depth by the committee, with participation from experienced clinicians and others in related fields. The final recommendations are based on the data available at the time of the production of the document and may be updated with pertinent scientific developments at a later time. The following guidelines are intended for adults and not for pediatric patients.

Risk factors for post-ERCP pancreatitis: a prospective multicenter study.

OBJECTIVES:Pancreatitis is the most common and serious complication of diagnostic and therapeutic ERCP. The aim of this study is to examine the potential patient- and procedure-related risk factors for post-ERCP pancreatitis in a prospective multicenter study.METHODS:A 160-variable database was prospectively collected by a defined protocol on patients undergoing diagnostic or therapeutic ERCP at 15 centers in the Midwest Pancreaticobiliary Group and participating in a randomized controlled study evaluating whether prophylactic corticosteroids will reduce the incidence of post-ERCP pancreatitis. Data were collected prior to the procedure, at the time of procedure, and 24–72 h after discharge. Post-ERCP pancreatitis was diagnosed and its severity graded according to consensus criteria.RESULTS:Of the 1,115 patients enrolled, diagnostic ERCP with or without sphincter of Oddi manometry (SOM) was performed in 536 (48.1%) and therapeutic ERCP in 579 (51.9%). Suspected sphincter of Oddi dysfunction (SOD) was the indication for the ERCP in 378 patients (33.9%). Pancreatitis developed in 168 patients (15.1%) and was graded mild in 112 (10%), moderate in 45 (4%), and severe in 11(1%). There was no difference in the incidence of pancreatitis or the frequency of investigated potential pancreatitis risk factors between the corticosteroid and placebo groups. By univariate analysis, the incidence of post-ERCP pancreatitis was significantly higher in 19 of 30 investigated variables. In the multivariate risk model, significant risk factors with adjusted odds ratios (OR) were: minor papilla sphincterotomy (OR: 3.8), suspected SOD (OR: 2.6), history of post-ERCP pancreatitis (OR: 2.0), age <60 yr (OR: 1.6), ≥2 contrast injections into the pancreatic duct (OR: 1.5), and trainee involvement (OR: 1.5). Female gender, history of recurrent idiopathic pancreatitis, pancreas divisum, SOM, difficult cannulation, and major papilla sphincterotomy (either biliary or pancreatic) were not multivariate risk factors for post-ERCP pancreatitis.CONCLUSION:This study emphasizes the role of patient factors (age, SOD, prior history of post-ERCP pancreatitis) and technical factors (number of PD injections, minor papilla sphincterotomy, and operator experience) as the determining high-risk predictors for post-ERCP pancreatitis.

EUS-guided rendezvous drainage of obstructed biliary and pancreatic ducts: Report of 6 cases.

BACKGROUND Only a few cases have been reported of EUS-guided drainage of obstructed pancreatic or bile ducts. An initial experience with EUS-guided rendezvous drainage after unsuccessful ERCP is reported. METHODS EUS-guided transgastric or transduodenal needle puncture and guidewire placement through obstructed pancreatic (n=4) or bile (n=2) ducts was attempted in 6 patients. Efforts were made to advance the guidewire antegrade across the papilla or surgical anastomosis. If guidewire passage was successful, rendezvous ERCP with stent placement was performed immediately afterward. RESULTS EUS-guided duct access and intraductal guidewire placement was accomplished in 5 of 6 cases, with successful traversal of the obstruction, and rendezvous ERCP, with stent placement in 3 of 6 cases (two biliary, one pancreatic). The procedure was clinically effective in all successful cases (two patients with malignant obstructive jaundice, one with relapsing pancreatitis after pancreaticoduodenectomy). There was one minor complication (transient fever) but no pancreatitis or duct leak after successful or unsuccessful procedures. CONCLUSIONS EUS is a feasible technique for allowing rendezvous drainage of obstructed biliary or pancreatic ducts through native papillae or anastomoses after initially unsuccessful ERCP.

Total Pancreatectomy and Islet Autotransplantation for Chronic Pancreatitis

BACKGROUND Total pancreatectomy (TP) with intraportal islet autotransplantation (IAT) can relieve pain and preserve β-cell mass in patients with chronic pancreatitis (CP) when other therapies fail. We report on a >30-year single-center series. STUDY DESIGN Four hundred and nine patients (including 53 children, 5 to 18 years) with CP underwent TP-IAT from February 1977 to September 2011 (etiology: idiopathic, 41%; Sphincter of Oddi dysfunction/biliary, 9%; genetic, 14%; divisum, 17%; alcohol, 7%; and other, 12%; mean age was 35.3 years, 74% were female; 21% has earlier operations, including 9% Puestow procedure, 6% Whipple, 7% distal pancreatectomy, and 2% other). Islet function was classified as insulin independent for those on no insulin; partial, if known C-peptide positive or euglycemic on once-daily insulin; and insulin dependent if on standard basal-bolus diabetic regimen. A 36-item Short Form (SF-36) survey for quality of life was completed by patients before and in serial follow-up since 2007, with an integrated survey that was added in 2008. RESULTS Actuarial patient survival post TP-IAT was 96% in adults and 98% in children (1 year) and 89% and 98% (5 years). Complications requiring relaparotomy occurred in 15.9% and bleeding (9.5%) was the most common complication. IAT function was achieved in 90% (C-peptide >0.6 ng/mL). At 3 years, 30% were insulin independent (25% in adults, 55% in children) and 33% had partial function. Mean hemoglobin A1c was <7.0% in 82%. Earlier pancreas surgery lowered islet yield (2,712 vs 4,077/kg; p = 0.003). Islet yield (<2,500/kg [36%]; 2,501 to 5,000/kg [39%]; >5,000/kg [24%]) correlated with degree of function with insulin-independent rates at 3 years of 12%, 22%, and 72%, and rates of partial function 33%, 62%, and 24%. All patients had pain before TP-IAT and nearly all were on daily narcotics. After TP-IAT, 85% had pain improvement. By 2 years, 59% had ceased narcotics. All children were on narcotics before, 39% at follow-up; pain improved in 94%; and 67% became pain-free. In the SF-36 survey, there was significant improvement from baseline in all dimensions, including the Physical and Mental Component Summaries (p < 0.01), whether on narcotics or not. CONCLUSIONS TP can ameliorate pain and improve quality of life in otherwise refractory CP patients, even if narcotic withdrawal is delayed or incomplete because of earlier long-term use. IAT preserves meaningful islet function in most patients and substantial islet function in more than two thirds of patients, with insulin independence occurring in one quarter of adults and half the children.

Adverse outcomes of ERCP

GASTROINTESTINAL ENDOSCOPY S273 ERCP has evolved from a diagnostic procedure into a primarily therapeutic procedure for a variety of biliary and pancreatic disorders. ERCP with or without associated biliary and pancreatic therapeutics can cause a variety of short-term complications including pancreatitis, hemorrhage, perforation, cardiopulmonary problems, and others (Table 1).1-11 These complications can range from minor with 1 or 2 days extra hospitalization and full recovery, to severe and devastating with permanent disability or death. Long-term sequelae of sphincterotomy and stents include recurrent stone formation, sphincter restenosis, cholecystitis, and ductal strictures.12-18 Advances in our understanding of adverse outcomes of ERCP have occurred in several areas: standardized consensus-based definitions of complications,10 refined understanding of risk factors for complications, and broadened concepts of positive and negative outcomes.

ERCP in patients with long-limb Roux-en-Y gastrojejunostomy and intact papilla

BACKGROUND ERCP by means of long-limb Roux-en-Y surgical anastomoses has been reported primarily in patients with biliary or pancreatic anastamoses, but rarely in patients with an intact papilla. METHODS All ERCP procedures attempted over a 6-year interval in patients with Roux-en-Y gastrojejunostomies and an intact papilla were reviewed. Patients with a prior Billroth II operation or alteration of the major papilla were excluded. Cannulation and therapy were primarily performed with a duodenoscope after exploration and placement of a guidewire in the afferent limb with a forward-viewing colonoscope. In some cases the duodenoscope was pulled into the afferent limb with a wire-guided balloon passed retrograde into the afferent limb. A follow-up of 30 days was obtained for all patients as part of a prospective ERCP outcome study. RESULTS Of 15 patients in whom ERCP was attempted, the papilla was reached in 10 patients (67%), the bile duct being accessed in all 10. Needle-knife precut papillotomy after placement of a pancreatic duct stent was performed in 3 patients. Biliary sphincterotomy with a variety of techniques was successful in all 9 patients in whom it was attempted. Other maneuvers included stone extraction, sphincter of Oddi manometry, and biliary stent placement. Final diagnoses were sphincter of Oddi dysfunction (6), malignant biliary stricture (2), choledocholithiasis plus tumor (1), and choledocholithiasis (1). Complications occurred after 3 (12%) of 25 ERCP procedures including pancreatitis (1 mild, 1 moderate) and bleeding (1 mild), all in patients with sphincter of Oddi dysfunction. CONCLUSIONS Diagnostic and therapeutic ERCP was ultimately successful in two thirds of patients with long-limb gastrojejunostomies and an intact papilla. The success of the ERCP is determined primarily by ability to advance a duodenoscope through the afferent limb. Once the major papilla was accessed with a duodenoscope, advanced biliary and pancreatic therapeutic techniques were feasible.

Interventions for Necrotizing Pancreatitis Summary of a Multidisciplinary Consensus Conference

Abstract Pancreatic and peripancreatic necrosis may result in significant morbidity and mortality in patients with acute pancreatitis. Many recommendations have been made for management of necrotizing pancreatitis, but no published guidelines have incorporated the many recent developments in minimally invasive techniques for necrosectomy. Hence, a multidisciplinary conference was convened to develop a consensus on interventions for necrotizing pancreatitis. Participants included most international experts from multiple disciplines. The evidence for efficacy of interventions was reviewed, presentations were given by experts, and a consensus was reached on each topic. In summary, intervention is primarily indicated for infected necrosis, less often for symptomatic sterile necrosis, and should ideally be delayed as long as possible, preferably 4 weeks or longer after the onset of disease, for better demarcation and liquefaction of the necrosis. Both the step-up approach using percutaneous drainage followed by minimally invasive video-assisted retroperitoneal debridement and per-oral endoscopic necrosectomy have been shown to have superior outcomes to traditional open necrosectomy with respect to short-term and long-term morbidity and are emerging as treatments of choice. Applicability of these techniques depends on the availability of specialized expertise and a multidisciplinary team dedicated to the management of severe acute pancreatitis and its complications.

Direct endoscopic necrosectomy for the treatment of walled-off pancreatic necrosis: results from a multicenter U.S. series

BACKGROUND Direct endoscopic necrosectomy (DEN) for treatment of walled-off pancreatic necrosis (WOPN) has been performed as an alternative to operative or percutaneous therapy. OBJECTIVE To report the largest combined experience of DEN performed for WOPN. DESIGN Retrospective chart review. SETTING Six U.S. tertiary medical centers. PATIENTS A total of 104 patients with a history of acute pancreatitis and symptomatic WOPN since 2003. INTERVENTIONS DEN for WOPN. MAIN OUTCOME MEASUREMENTS Resolution or near-resolution of WOPN without the need for surgical or percutaneous intervention and procedural complications. RESULTS Successful resolution was achieved in 95 of 104 patients (91%). Of the patients in whom it failed, 5 died during follow-up before resolution, 2 underwent operative drainage for persistent WOPN, 1 required surgery for massive bleeding on fistula tract dilation, and 1 died periprocedurally. The mean time to resolution from the initial DEN was 4.1 months. The first débridement was performed a mean of 63 days after the initial onset of acute pancreatitis. In 73%, the entry was transgastric with median tract dilation diameter of 18 mm. The median number of procedures was 3 with 2 débridements. Complications occurred in approximately 14% and included 5 retrogastric perforations/pneumoperitoneum, which were managed nonoperatively. Univariate analysis identified a body mass index >32 as a risk factor for failed DEN. LIMITATIONS Retrospective, highly specialized centers. CONCLUSIONS This large, multicenter series demonstrates that transmural, minimally invasive endoscopic débridement of WOPN performed in the United States is an efficacious and reproducible technique with an acceptable safety profile.

Pancreatic stent insertion: consequences of failure and results of a modified technique to maximize success

BACKGROUND Increasingly, pancreatic stents are being placed to prevent post-ERCP pancreatitis. However, guidewire and stent placement may fail if the duct is small or tortuous, potentially exacerbating the risk. This study assessed the impact of unsuccessful pancreatic stent placement on complications and the efficacy of a modified technique for stent insertion when pancreatic ductal anatomy makes stent insertion technically difficult. METHODS Technical variables and 30-day complications of consecutive therapeutic ERCPs, including attempted major papilla pancreatic stent insertion were prospectively studied. Success rates for pancreatic stent placement were compared for a 1-year period during which conventional deep guidewire insertion was used and another 1-year period in which a modified technique was used as needed in patients with ductal anatomy that made stent placement technically difficult. In the modified technique, a short (2-3 cm) small diameter (3F-5F) stent was placed over a 0.018-in nitinol-tipped guidewire, passed as little as 1 to 2 cm beyond the pancreatic sphincter. RESULTS In 225 high-risk therapeutic ERCPs, pancreatitis occurred after the procedure in two of 3 (66.7%) patients in whom pancreatic stent insertion failed vs. 32 of 222 (14.4%) patients with successful insertion (p=0.06). Severe pancreatitis occurred only after unsuccessful stent insertion. Significant multivariate risk factors for post-ERCP pancreatitis were unsuccessful pancreatic stent insertion (odds ratio 16.1: 95% CI[1.3, 200]), sphincter of Oddi dysfunction (odds ratio 3.2: 95% CI[1.4, 7.5]), and prior post-ERCP pancreatitis (odds ratio 3.2: 95% CI[1.4, 7.1]). The following were not risk factors: performance of pancreatic, biliary, or needle-knife pre-cut sphincterotomy; number of pancreatic contrast injections; and difficult cannulation. Stent placement was unsuccessful in 3 (3.2%) of 93 attempts during the 1-year period in which a conventional technique was used vs. none of 132 attempts in a subsequent year in which the modified technique was used. CONCLUSIONS Failed attempts at pancreatic stent placement are associated with an extremely high risk of post-ERCP pancreatitis. Success can be consistently achieved by use of a modified technique.

Plastic versus self-expanding metallic stents for malignant hilar biliary obstruction: a prospective multicenter observational cohort study.

Background There are few comparative data as to whether plastic or self-expanding metallic stents are preferable for palliating malignant hilar biliary obstruction. Methods Thirty-day outcomes of consecutive endoscopic retrograde cholangiopancreatographies performed for malignant hilar obstruction at 6 private and 5 university centers were assessed prospectively. Results Patients receiving plastic (N=28) and metallic stents (N=34) were similar except that metallic stent recipients more often had: Bismuth III or IV tumors (16/34 vs. 5/28 P=0.043), higher Charlson comorbidity scores (P=0.003), metastatic disease (P=0.006), and management at academic centers (P=0.018). The groups had similar rates of bilateral stent placement (4/28 vs. 5/34), and similar frequency of opacified but undrained segmental ducts (7/28 vs. 5/34). Adverse outcomes including cholangitis, stent occlusion, migration, perforation, and/or the need for unplanned endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography occurred in 11/28 (39.3%) patients with plastic versus 4/34 (11.8%) with metal stents (P=0.017). By logistic regression, factors associated with adverse outcomes included plastic stent placement (odds ratio 6.32; 95% confidence interval 1.23, 32.56) and serum bilirubin (1.11/mg/dL above normal: 1.01, 1.22) but not center type or Bismuth class. Conclusions Metallic stent performance was superior to plastic for hilar tumor palliation with respect to short-term outcomes, independent of disease severity, Bismuth class, or drainage quality.