IAP Guidelines for the Surgical Management of Acute Pancreatitis

Transcription

1 Guidelines These guidelines have been prepared by the International Society of Pancreatology. They represent a consensus of best practice on the available evidence at the time of preparation. They may not apply in all situations and should be interpreted in the light of specific clinical situations and resource availability. : Pancreatology 2002;2: DOI: / Published online: November 14, 2002 Waldemar Uhl a Andrew Warshaw b Clement Imrie c Claudio Bassi d Colin J. McKay c Paul G. Lankisch e Ross Carter c Eugene Di Magno f Peter A. Banks g David C. Whitcomb h Christos Dervenis i Charles D. Ulrich j Kat Satake k Paula Ghaneh l Werner Hartwig a Jens Werner a Gerry McEntee m John P. Neoptolemos l Markus W. Büchler a a Department of General Surgery, University of Heidelberg, Germany; b Department of Surgery, Massachusetts General Hospital, Boston, Mass., USA; c Lister Department of Surgery, Glasgow Royal Infirmary, Glasgow, UK; d Endocrinochirurgia, University of Verona, Policlinico B. Roma, Verona, Italy; e Medizinische Klinik, Städtisches Klinikum Lüneburg, Germany; f Department of Gastroenterology, Mayo Clinic, Rochester, Minn., USA; g Department of Gastroenterology, Brigham and Women s Hospital, Boston, Mass., USA; h Department of Medicine, University of Pittsburgh, Pa., USA; i Department of Surgery, Agia Olga Hospital, Athens, Greece; j Department of Medicine, University of Cincinnati, Ohio, USA; k First Department of Surgery, Osaka City University Medical School, Osaka, Japan; l Department of Surgery, University of Liverpool, UK, and m Department of Surgery, Mater Misericordiae Hospital, Dublin, Ireland Abstract During 2002 the International Association of Pancreatology developed evidenced-based guidelines on the surgical management of acute pancreatitis. There were 11 guidelines, 10 of which were recommendations grade B and one (the second) grade A. (1) Mild acute pancreatitis is not an indication for pancreatic surgery. (2) The use of prophylactic broad-spectrum antibiotics reduces infection rates in computed tomography-proven necrotizing pancreatitis but may not improve survival. (3) Fine-needle aspiration for bacteriology should be performed to differentiate between sterile and infected pancreatic necrosis in patients with sepsis syndrome. (4) Infected pancreatic necrosis in patients with clinical signs and symptoms of sepsis is an indication for intervention including surgery and radiological drainage. (5) Patients with sterile pancreatic necrosis (with negative fine-needle aspiration for bacteriology) should be managed conservatively and only undergo intervention in selected cases. (6) Early surgery within 14 days after onset of the disease is not recommended in patients with necrotizing pancreatitis unless there are specific indications. (7) Surgical and other forms of interventional management should favor an organ-preserving approach, which involves debridement or necrosectomy combined with a postoperative management concept that maximizes postoperative evacuation of retroperitoneal debris and exudate. (8) Cholecystectomy should be performed to avoid recurrence of gallstone-associated acute pancreatitis. (9) In mild gallstone-associated acute pancreatitis, cholecystectomy should be performed as soon as the patient has recovered and ideally during the same hospital admission. (10) In severe gallstone-associated acute pancreatitis, cholecystectomy should be delayed until there is sufficient resolution of the inflammatory response and clinical recovery. (11) Endoscopic sphincterotomy is an alter- ABC Fax karger@karger.ch S. Karger AG, Basel and IAP /02/ $18.50/0 Accessible online at: Markus W. Büchler, MD Department of General Surgery, University of Heidelberg Im Neuenheimer Feld 110, D Heidelberg (Germany) Tel , Fax markus_buechler@med.uni-heidelberg.de

2 native to cholecystectomy in those who are not fit to undergo surgery in order to lower the risk of recurrence of gallstone-associated acute pancreatitis. There is however a theoretical risk of introducing infection into sterile pancreatic necrosis. These guidelines should now form the basis for audit studies in order to determine the quality of patient care delivery. Copyright 2002 S. Karger AG, Basel and IAP Introduction and Purpose of Guidelines The necessity for surgical intervention in patients with acute pancreatitis has been controversial for more than 100 years, varying between a conservative medical approach on the one hand and a surgical approach on the other. In the past 15 years there has been a great leap in knowledge of the natural history of acute pancreatitis [1 3] and at the same time major advances in imaging of the pancreas [4]. Thus it has become possible to classify the severity of the disease and to assess the evolution of pancreatitis in real time [5]. This has enabled the objective assessment of various new approaches designed with the objective of significantly reducing the mortality of this dreadful disease [6]. During recent years the management of acute pancreatitis has changed. This has been due particularly in response to the general availability of computed tomography, improved intensive care facilities, knowledge about the central role of pancreatic infection and refinements in surgical and other interventional techniques [1, 4 6]. The present guidelines of the International Association of Pancreatology (IAP) address the role of the surgical management of acute pancreatitis including the indications, the timing and the techniques of surgery. These guidelines describe the highest standards of the surgical management of acute pancreatitis based on currently published studies. Methods of Formulation of the Guidelines The Process A preliminary manuscript that was based on an extended literature search (Medline and Cochrane Library) of published reports was prepared and key recommendations proposed. The evidence and key recommendations were discussed at a special symposium of the IAP (Acute Pancreatitis: Indications for Surgery IAP Guidelines Development) held on June 22, 2002 during the joint meeting of the International Association of Pancreatology and European Pancreatic Club (June 19 22, 2002) in Heidelberg, Germany. During the symposium key note lectures were given followed by intense discussions on the following topics: natural history of necrotizing pancreatitis; when to be concerned about severe acute pancreatitis; the natural course of organ failure in acute pancreatitis; radiological and clinical indications for surgical intervention; the role of markers for monitoring disease progression; outcome of open necrosectomy; and the results of minimally invasive necrosectomy. Manuscripts representing the groups of invited speakers for the aforementioned presentations were submitted to Pancreatology for peer-review prior to publication and should be read in conjunction with the IAP Guidelines. Each of the proposed recommendations was discussed and an initial consensus was reached. The process involved excluding proposed or introducing new recommendations and agreeing on the precise wording of each of the recommendations. The draft manuscript was amended accordingly. The guidelines were then distributed to the key clinicians for approval or for further modifications, with all agreeing on the final version. These guidelines were then sent to all members of the IAP Council (2002) for approval and/or modifications. All parties concerned approved the final guidelines. The list of clinicians who were directly responsible for these guidelines together with those who were consulted at a later stage of their production is given at the end. Finally the IAP Guidelines were submitted to Pancreatology for peer-review prior to publication. Categories of Evidence The present guidelines have been produced to conform to established evidence-based guideline criteria [7 10]. The strength of evidence used in the formulation of these guidelines was graded according to the following system: Ia = Evidence obtained from meta-analysis of randomized controlled trials. Ib = Evidence obtained from at least one randomized controlled trial. IIa = Evidence obtained from at least one well-designed controlled study without randomization. IIb = Evidence obtained from at least one type of well-designed quasi-experimental study. III = Evidence obtained from well-designed non-experimental descriptive studies such as comparative studies, correlation studies and case studies. IV = Evidence obtained from expert committee report or opinions or clinical experiences of respected authorities. Grading of Recommendations The strength of each recommendation depends on the category of the evidence supporting it and is graded according to the following system: Grade A = Strong evidence that requires a meta-analysis of randomized controlled trials or at least one randomized controlled trial (evidence categories Ia, Ib). Grade B = Intermediate evidence, requires non-randomized clinical studies (evidence categories IIa, IIb, III). Grade C = Low evidence, requires evidence from expert committee reports or opinions or clinical experiences of respected authorities, in the absence of directly applicable clinical studies of good quality (evidence categories IV). Pancreatology 2002;2: Uhl et al.

3 The International Association of Pancreatology Guidelines for the Surgical Management of Acute Pancreatitis Clinical Course of Acute Pancreatitis Mild Pancreatitis Most episodes of acute pancreatitis (80%) are mild and self-limiting, subsiding spontaneously within 3 5 days. The mortality rate is less than 1% and these patients normally do not need intensive care treatment and pancreatic surgery [6, 11 13]. Recommendation 1: Mild acute pancreatitis is not an indication for pancreatic surgery (recommendation Severe Pancreatitis In 10 20% of the cases, however, severe disease develops and parts of the pancreas and surrounding tissue become necrotic. Severe pancreatitis, in general, progresses in two phases. The first 2 weeks after the onset of symptoms the disease is characterized by the systemic inflammatory response syndrome (SIRS). The release of proinflammatory mediators is supposed to contribute to the pathogenesis of SIRS-associated pulmonary, cardiovascular, and renal insufficiency. It is important to understand that SIRS in the early phase of severe pancreatitis may be found in the absence of significant pancreatic necrosis and is frequently found in the absence of pancreatic infection [14, 15]. Infection of pancreatic necrosis naturally develops during the second phase of the disease (most commonly in the 2nd and 3rd week after the onset of symptoms) and has been reported in as many as 40 70% of patients with necrotizing pancreatitis [16 18]. The risk of infection increases with the extent of intra- and extra-pancreatic necrosis [16, 19]. Even with the use of prophylactic antibiotic therapy (prescribed in the absence of proven sepsis), infection of pancreatic necrosis is still a major risk factor in severe pancreatitis, whilst sepsis-related multiple organ failure is the main life-threatening complication with a mortality rate of 20 50% [19 22]. It is estimated that infected pancreatic necrosis will develop in about one third of patients who have been placed on broad-spectrum antibiotics that penetrate the pancreas and have the appropriate spectrum of activity against the microorganisms commonly found in necrotizing pancreatitis. With increasing use of antibiotics there has been a relative shift from predominantly gram-negative bacteria towards a higher incidence of infection with gram-positive bacteria and fungi 2 3 weeks after the start of antibiotic therapy [3]. Several randomized controlled trials have provided evidence that prophylactic antibiotics may prevent the development of septic complications [23 25] or a reduction in mortality [26] in severe acute pancreatitis. Interpretation of the individual trials is not straightforward: all 3 trials that showed a reduction in pancreatic sepsis showed no difference in survival, perhaps because they were underpowered [23 25], and the 1 trial that showed a reduction in mortality had an uneven distribution of early deaths and no reduction in pancreatic sepsis [26]. Two meta-analyses based on these data [27, 28] showed a beneficial effect from prophylactic antibiotics, both with regard to the development of infection and mortality. Recommendation 2: The use of prophylactic broadspectrum antibiotics reduces infection rates in CT-proven necrotizing pancreatitis but may not improve survival (recommendation grade A). Once pancreatic necrosis has developed, the differentiation between sterile and infected necrosis is essential for the management of patients. Fine-needle aspiration for bacteriology (FNAB) of pancreatic or peripancreatic necrosis has been established as an accurate, safe and reliable technique for the identification of infected necrosis [17, 29, 30]. FNAB can be guided by either computed tomography or ultrasonography and should be performed in patients who develop significant pancreatic necrosis and clinical signs of sepsis. The complication rate of this procedure is low [29, 30], with a very low incidence of serious complications such as bleeding or exacerbation of acute pancreatitis [31, 32]. Bacterial tests including gram staining and culture of the aspiration material have a diagnostic sensitivity and specificity of 88 and 90%, respectively [33]. It is important that only those patients who develop clinical signs of sepsis should undergo FNAB, since the procedure bears a potential risk of secondary infection [3, 6, 33]. Recommendation 3: FNAB should be performed to differentiate between sterile and infected pancreatic necrosis in patients with sepsis syndrome (recommendation Management of Infected Necrosis Proven infected pancreatic necrosis as well as septic complications directly resulting from pancreatic infection are indications for surgical treatment [6, 12, 34, 35]. The mortality rate for patients with infected pancreatic necrosis is higher than 30%, and up to 80% of fatal outcomes in acute pancreatitis are due to septic complications [16, 20, 36]. The conservative management of infected pancreatic necrosis associated with multiple organ failure has a mortality rate of up to 100% [37]. In contrast the surgical treatment of patients with infected pancreatic necrosis is Pancreatology 2002;2:

4 associated with mortality rates that are as low as 10 30% in some specialized centers [6, 38, 39]. Recommendation 4: Infected pancreatic necrosis in patients with clinical signs and symptoms of sepsis is an indication for intervention including surgery and radiological drainage (recommendation Management of Sterile Necrosis Whereas infected pancreatic necrosis is a clear indication for surgery, the management of sterile pancreatic necrosis is still a matter of controversy. Most patients with sterile necrosis respond to conservative non-surgical medical management [6, 38]. Nevertheless, some patients do not improve despite maximal therapy in the intensive care unit (ICU) and the role of surgery remains debatable in those patients who develop organ failure associated with sterile pancreatic necrosis [14, 40 44]. In a retrospective series of 172 patients with sterile necrosis [42], 62% of patients were managed surgically whereas the remainder was treated conservatively. The mortality rate was not significantly different between the 2 groups: 13.1% for the surgically treated patients and 6.2% for those treated non-surgically. The surgical group, however, was characterized by higher Ranson and Apache II scores and higher serum levels of C-reactive protein on admission. It was concluded that persistent or progressive organ complications despite maximal ICU treatment was an indication for surgery in patients with sterile necrosis. The experience of the Ulm group is that the extent of pancreatic necrosis is related to organ failure (and hence mortality) in sterile pancreatic necrosis, whilst the incidence of organ failure is relatively high in infected pancreatic necrosis regardless of the extent of pancreatic necrosis [19]. On the other hand the Boston (Massachusetts General Hospital) group have an equally low mortality for both infected and sterile pancreatic necrosis [39, 43]. These data suggest wide variations in the types of patients operated upon that cannot be adequately compared using the present systems of disease severity classification. Fulminant acute pancreatitis is characterized by rapidly progressive multiple organ failure in the first few days following the onset of acute pancreatitis with a high probability of death despite ICU therapy. There is a poor outcome with both surgical and conservative therapies [45, 46]. In selected cases however, such as persistent organ complications or severe clinical deterioration despite ICU therapy, surgery may be indicated in sterile necrosis [42]. Recommendation 5: Patients with sterile pancreatic necrosis (FNAB negative) should be managed conservatively and only undergo intervention in selected cases (recommendation Timing of Surgery Patients with severe pancreatitis can progress to a critical condition within a few hours or days after the onset of symptoms. In the early course of the disease, patients are at high risk of death from cardiovascular or pulmonary failure. In the past, early surgical intervention was favored especially in the presence of deteriorating systemic organ function but mortality rates of up to 65% were experienced [45, 47, 48], questioning the benefit of surgical intervention within the first few days after the onset of symptoms. At present, there is general agreement that surgery in severe pancreatitis should be deferred whilst patients continue to respond positively to conservative management. The rationale for delaying surgical therapy is to permit proper demarcation of pancreatic and peripancreatic necrosis to occur. The 3rd or 4th week after the onset of the disease is generally agreed to provide the optimal operative conditions for necrosectomy, with the effect of limiting the extent of surgery that is needed to facilitate debridement. This approach decreases the risk of bleeding and minimizes the surgery-related loss of vital tissue that predisposes to surgery-induced endocrine and exocrine pancreatic insufficiency. In the only prospective randomized trial comparing early (within 72 h of symptoms) with late (at least 12 days after onset) pancreatic resection/ debridement in patients with severe pancreatitis, the mortality rates were 56 and 27%, respectively [48]. Although the difference did not reach statistical significance, the trial was terminated because of concern about the very high mortality of early surgery. Recommendation 6: Early surgery within 14 days after onset of the disease is not recommended in patients with necrotizing pancreatitis unless there are specific indications (recommendation Surgical Procedures The aim of surgery in patients with necrotizing pancreatitis is to remove all areas of necrotic tissue including necrotic pancreatic tissue and any infected necrotic tissue. In so doing the risk of further complications may be minimized by reducing the progress of spreading necrosis and/ or infection and the release of proinflammatory mediators. Unlike debridement, resection procedures such as partial or total pancreatectomy that also remove vital pancreatic tissue and/or healthy organs are associated with high mortality rates, as well as increasing the risk of Pancreatology 2002;2: Uhl et al.

5 postoperative exocrine and endocrine insufficiency [45, 49 51]. The surgical techniques for the treatment of pancreatic necrosis are varied and the ideal method is still debated. Generally agreed principles of surgical management include an organ-preserving approach which involves debridement or necrosectomy, minimization of intra-operative hemorrhage and maximization of postoperative removal of retroperitoneal debris and exudate. Three techniques are available with apparently comparable results: (i) open necrosectomy with closed continuous lavage of the retroperitoneum [41, 52]; (ii) open necrosectomy that may or may not be staged with planned re-laparotomies followed by delayed primary closure and drainage or with multiple drainage and re-laparotomy as required [35, 43, 44], and (iii) open necrosectomy with open packing and planned re-laparotomies [53]. It is reported that these approaches are associated with a postoperative mortality of less than 15% but there has never been a trial that has ever prospectively compared these techniques. Novel approaches to treat pancreatic necrosis have been introduced including percutaneous techniques using radiological guidance either alone or in combination with minimally invasive techniques [54 57]. Although several specialized centers have reported that patients with acute pancreatitis may be managed by percutaneous catheter drainage or percutaneous necrosectomy, many patients have required subsequent laparotomy to control sepsis [54 57]. It has been proposed that these minimally invasive techniques are most suited for a subgroup of patients with localized and/or well-organized pancreatic necrosis, but these different approaches can only be properly compared in randomized controlled trials. Recommendation 7: Surgical and other forms of interventional management should favor an organ-preserving approach which involves debridement or necrosectomy combined with a postoperative management concept that maximizes postoperative evacuation of retroperitoneal debris and exudate (recommendation Gallstone-Associated Acute Pancreatitis In Western countries, acute pancreatitis is associated with the presence of gallstones in 40 60% of cases [12, 58]. There is strong evidence that gallstones initiate an episode of pancreatitis by temporary or persistent obstruction of the distal common bile duct orifice at the ampulla of Vater, although the exact pathogenesis of subsequent pancreatic inflammation remains unclear [59 61]. Once the diagnosis of gallstone pancreatitis is established, the further management will depend on the severity of the attack and the presence of obstructive jaundice and/or acute cholangitis [62 65]. Endoscopic Retrograde Cholangiopancreatography and Endoscopic Sphincterotomy to Improve the Outcome from a Severe Attack It may be important to determine rapidly whether gallstones are the cause of a severe attack, since endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (ES) may ameliorate symptoms and the progression of the disease. Failure of the patient s condition to improve within 48 h despite intensive initial resuscitation is considered by some to be an indication for urgent ERCP and ES in gallstone-associated acute pancreatitis [62, 63]. Both the United Kingdom and Hong Kong groups who undertook the first randomized controlled trials of ERCP and ES in gallstone-associated acute pancreatitis favor early intervention in severe acute pancreatitis regardless of the presence of obstructive jaundice and/or acute cholangitis. The results of a 3rd randomized controlled trial of ERCP and ES in gallstone-associated acute pancreatitis from Germany suggested that ERCP and ES should be restricted to patients with biliary sepsis or obstructive jaundice and that, in the absence of these clinical features, severity alone was not an indication for ERCP and ES [64]. Why the results of the German trial differ from the other 2 trials [62, 63] remains a matter of debate [66, 67]. Given the lack of a clear consensus on this subject, no recommendation can be made on the use of ERCP and ES in severe gallstone-associated acute pancreatitis per se, although all are agreed that ERCP and ES are indicated in the presence of obstructive jaundice and/or acute cholangitis. Role for Emergency Surgery Kelly and Wagner [68] assigned 165 patients with acute gallstone-associated pancreatitis to early surgery (within 48 h after admission) or delayed surgery (more than 48 h after admission). Early surgery was associated with a much higher morbidity (83 versus 48%, respectively) and mortality rate (18 versus 12%, respectively) in patients with severe pancreatitis than delayed surgery. Although there is much that can be criticized about this trial, there is general agreement that open cholecystectomy with supraduodenal bile duct exploration and insertion of a T tube is an unacceptable emergency procedure in patients with severe gallstone-associated acute pancreatitis. It is widely accepted that whilst comorbidity is a major predeterminant of outcome from cholecystectomy, Pancreatology 2002;2:

6 this factor does not apply to the use of ERCP and ES [69]. If a patient has had an endoscopic sphincterotomy during the course of an attack of gallstone-associated acute pancreatitis consideration should be given to removing the gallbladder as these patients have a relatively high risk of subsequent gallbladder symptoms [70 74]. Surgery to Prevent Further Attacks Recurrence of acute pancreatitis in patients with gallstones has been reported in 29 63% of cases if the patient is discharged from the hospital without additional treatment [75 77]. The rationale for cholecystectomy and clearance of the main bile duct in these patients is to prevent potentially avoidable recurrent biliary pancreatitis. The timing of cholecystectomy depends on the clinical situation. In mild gallstone-associated acute pancreatitis cholecystectomy should be performed as soon as the patient has recovered from the attack and preferably during the same hospital stay [12, 78, 79]. In severe gallstoneassociated acute pancreatitis, cholecystectomy should be undertaken once the inflammatory process has subsided and with sufficient clinical recovery to make the procedure technically easier and safer for the patient [80 82]. Cholecystectomy can be performed safely after an episode of gallstone-associated acute pancreatitis has resolved by a laparoscopic approach [79, 80, 83]. The success rate of the laparoscopic approach is between 80 and 100%, with a conversion rate of between 0 and 16%. Recommendation 8: Cholecystectomy should be performed to avoid recurrence of gallstone-associated acute pancreatitis (recommendation Recommendation 9: In mild gallstone-associated acute pancreatitis cholecystectomy should be performed as soon as the patient has recovered and ideally during the same hospital admission (recommendation Recommendation 10: In severe gallstone-associated acute pancreatitis, cholecystectomy should be delayed until there is sufficient resolution of the inflammatory response and clinical recovery (recommendation Endoscopic Sphincterotomy to Prevent Further Attacks Following an attack of either mild or severe gallstoneassociated acute pancreatitis the patient may not be fit to undergo cholecystectomy. In these circumstances elective prophylactic endoscopic sphincterotomy (whether there are or are not any stones in the main bile ducts) is an important option. In 5 series with a total of 109 patients with median follow-up times of months, only 1 (0.9%) developed a further attack of acute pancreatitis although 8 (7.9%) patients developed subsequent biliary symptoms [70, 72, 84 86]. There is a theoretical risk of introducing infection into sterile necrosis during the endoscopic sphincterotomy procedure although reports in the literature are lacking. In these circumstances complete resolution of the necrosis may be advised before undertaking the endoscopic sphincterotomy. Recommendation 11: Endoscopic sphincterotomy is an alternative to cholecystectomy in those who are not fit to undergo surgery in order to lower the risk of recurrence of biliary pancreatitis. There is, however, a theoretical risk of introducing infection into sterile pancreatic necrosis (recommendation Summary of the International Association of Pancreatology Audit Goals for the Surgical The following is a summary of the official IAP guidelines on the surgical management of acute pancreatitis. The grading of each recommendation is given and these are based on the evidence reviewed in the text. These guidelines should now form the basis for audit studies in order to determine the quality of patient care delivery. 1 Mild acute pancreatitis is not an indication for pancreatic surgery (recommendation 2 The use of prophylactic broad-spectrum antibiotics reduces infection rates in CT-proven necrotizing pancreatitis but may not improve survival (recommendation grade A). 3 FNAB should be performed to differentiate between sterile and infected pancreatic necrosis in patients with sepsis syndrome (recommendation 4 Infected pancreatic necrosis in patients with clinical signs and symptoms of sepsis is an indication for intervention including surgery and radiological drainage (recommendation 5 Patients with sterile pancreatic necrosis (FNAB negative) should be managed conservatively and only undergo intervention in selected cases (recommendation 6 Early surgery within 14 days after onset of the disease is not recommended in patients with necrotizing pancreatitis unless there are specific indications (recommendation 7 Surgical and other forms of interventional management should favor an organ-preserving approach, which involves debridement or necrosectomy com- Pancreatology 2002;2: Uhl et al.

7 bined with a postoperative management concept that maximizes postoperative evacuation of retroperitoneal debris and exudate (recommendation 8 Cholecystectomy should be performed to avoid recurrence of gallstone-associated acute pancreatitis (recommendation 9 In mild gallstone-associated acute pancreatitis cholecystectomy should be performed as soon as the patient has recovered and ideally during the same hospital admission (recommendation 10 In severe gallstone-associated acute pancreatitis, cholecystectomy should be delayed until there is sufficient resolution of the inflammatory response and clinical recovery (recommendation 11 Endoscopic sphincterotomy is an alternative to cholecystectomy, in those who are not fit to undergo surgery in order to lower the risk of recurrence of gallstoneassociated acute pancreatitis. There is, however, a theoretical risk of introducing infection into sterile pancreatic necrosis (recommendation Acknowledgements The following were participants at the IAP meeting to discuss the Guidelines on June 22nd 2002 and made active contributions to their formulation Brazil: Jose Eduardo Cunha, Sonia Penteado (Sao Paulo); Bulgaria: Oleg Tcholakav (Sofia); Czech Republic: Peter Balaz (Prague); Denmark: Steen Larsen (Glostrup), Else K Philipsen (Bispebjerg); Finland: Marko Lempinen (Helsinki); France: René Laugier (Marseille); Germany: Hans-Guenter Becker (Kaiserslautern), Pascal Berberat, Markus W. Buechler, Fabio F. Di Mola, Pierluigi Di Sebastiano, Ahmed Guweidhi, Mark Hartel, Werner Hartwig, Jorg Kleeff, Christophe Mueller, Bruno Schmied, Waldemar Uhl, Jens Werner (Heidelberg), Tobias Keck (Freiburg); Greece: E. Chatzitheoklitos (Thessaloniki), Gregory Tsiotos (Athens); Hungary: Laszlo Czako, Tamas Takacs (Szeged), D. Dezso Kelemen (Pecs), Attila Olah (Györ), Tibor F. Tihanyi (Hungary); Ireland: Gerry McEntee (Dublin); Italy: Claudio Bassi (Verona); Japan: Kat Satake (Osaka), Tooru Shimosegawa (Sendai); Mexico: Guillermo Robles- Diaz, Andres Duarte-Rojo (Mexico DF); : Andrzej Dabrowski, Jan Dlugosz, Wereszczynska-Sremietkowska (Bialystok), Zycmuni Warzecha (Krakow); Portugal, Antonio Marques (Lisbon), Faustino P Reis (Amarente); Romania: Barbu Traian-Sorin (Cluj-Napoca); Slovenia: Alojz Pleskovic (Ljubljana); Spain: J. Enrique Dominguez- Munoz, Julio Iglesias Garcia, Augusto Villanueva (Santiago De Compostela), Luisa Guarner, Donald-Jose Vasquez-Cruz (Barcelona), Miguel Perez-Mateo (Alicante); Sweden: Anders Borgstöm (Malmö), Fernando Ruizjasbon (Göthenburg), Berit Sternby (Lund); Switzerland; Beat Gloor (Bern); UK: Malcolm Aldridge (Welwyn Garden City), Derek O Reilly, Paula Ghaneh, John P. Neoptolemos (Liverpool), Peter Hegyi (Newcastle), Clement Imrie, Colin J. McKay (Glasgow), Rohit Makhija (Plymouth), Mark Midwinter (Southampton), Satvinder S. Mudan (London), Ioannis Virlos (London); Ukraine: Andre A. Perejaslov, Roman E. Vatseba (Lviv); USA: Peter A. Banks, Andrew L. Warshaw (Boston), Woody Denham (Chicago), E.P. DiMagno (Rochester), William H. Nealon (Galveston), Charles D. Ulrich (Cincinnati), David Whitcomb (Pittsburgh); Yugoslavia: Tamara Alempijevic, Knezevic Djordje, Lili Petronijevic, Dejad Radeukovic, Dugalic Vladimir (Belgrade). The following IAP Council members reviewed and approved the final version of the IAP Guidelines: Prof. J.P. Neoptolemos, Liverpool, UK (President); Prof. A.L. Warshaw, Boston, USA (Past-President); Prof. S. Matsuno, Sendai, Japan (President-Elect); Prof. P.G. Lankisch, Lüneburg, Germany (Secretary); Prof. M. Büchler, Heidelberg, Germany (Treasurer); Prof. K. Kashima, Kyoto, Japan (Co- Treasurer); Prof. M.V. Singer, Mannheim, Germany and Prof. C.W. Imrie, Glasgow, UK (Co-Editors, Pancreatology); Prof. C. Bassi, Verona, Italy; Prof. P. Bornman, Cape Town, South Africa; Prof. E. Dominguez-Monoz, Santiago de Compostela, Spain; Dr. C.F. del Castillo, Boston, USA; Prof. K. Inoue, Kyoto, Japan; Prof. M. Lerch, Münster, Germany; Prof. P. Levy, Clichy, France; Prof. J.E. Monteiro Cunha, Brazil; Prof. A. Pap, Budapest, Hungary; Prof. R. Pezzili, S. Lazzaro di Savena, Italy; Prof. C. Pitchumoni, New York, USA; Prof. G. Robles-Diaz, Co Toriello-Guerral, Mexico; Prof. K. Satake, Youkouchoi Ashiya, Japan; Prof. R. Schmid, Heidelberg, Germany; Prof. T. Shimosegawa, Sendai, Japan; Prof. M. Tempero, San Francisco, USA; Dr. G.G. Tsiotos, Athens, Greece; Dr. M. Vaccaro, Buenos Aires, Argentina; Prof. D. Whitcomb, Pittsburgh, USA; Prof. J. Wilson, New South Wales, Australia. References 1 Isenmann R, Beger HG: Natural history of acute pancreatitis and the role of infection. Baillieres Best Pract Res Clin Gastroenterol 1999;13: Uhl W, Büchler MW, Malfertheiner P, Beger HG, Adler G, Gaus W: A randomised, double blind, multicentre trial of octreotide in moderate to severe acute pancreatitis. Gut 1999;45: Gloor B, Müller CA, Worni M, et al: Pancreatic infection in severe pancreatitis: The role of fungus and multiresistant organisms. Arch Surg 2001;136: Balthazar EJ, Robinson DL, Megibow AJ, Ranson JH: Acute pancreatitis: Value of CT in establishing prognosis. Radiology 1990;174: Bradley EL: A clinically based classification system for acute pancreatitis. Summary of the International Symposium on Acute Pancreatitis, Atlanta, Ga., September 11 13, Arch Surg 1993;128: Büchler MW, Gloor B, Müller CA, Friess H, Seiler CA, Uhl W: Acute necrotizing pancreatitis: Treatment strategy according to the status of infection. Ann Surg 2000;232: Woolf SH: Practice guidelines, a new reality in medicine. II. Methods of developing guidelines. Arch Intern Med 1992;152: Woolf SH: Practice guidelines: A new reality in medicine. III. Impact on patient care. Arch Intern Med 1993;153: Eccles M, Clapp Z, Grimshaw J, et al: North of England evidence based guidelines development project: Methods of guideline development. BMJ 1996;312: Grimshaw J, Eccles M, Russell I: Developing clinically valid practice guidelines. J Eval Clin Pract 1995;1: Pancreatology 2002;2:

8 11 Rünzi M, Layer P, Büchler MW, et al: The therapy of acute pancreatitis. General guidelines. Working group of the Society for Scientific-Medical Specialties. Z Gastroenterol 2000;38: British Society of Gastroenterology: United Kingdom guidelines for the management of acute pancreatitis. Gut 1998;42(suppl 2):S1 S Winslet M, Hall C, London NJ, Neoptolemos JP: Relation of diagnostic serum amylase levels to aetiology and severity of acute pancreatitis. Gut 1992;33: Tenner S, Sica G, Hughes M, et al: Relationship of necrosis to organ failure in severe acute pancreatitis. Gastroenterology 1997;113: Lankisch PG, Pflichthofer D, Lehnick D: No strict correlation between necrosis and organ failure in acute pancreatitis. Pancreas 2000;20: Beger HG, Bittner R, Block S, Büchler M: Bacterial contamination of pancreatic necrosis. A prospective clinical study. Gastroenterology 1986;91: Gerzof SG, Banks PA, Robbins AH, et al: Early diagnosis of pancreatic infection by computed tomography-guided aspiration. Gastroenterology 1987;93: Bassi C, Falconi M, Girelli F, et al: Microbiological findings in severe pancreatitis. Surg Res Commun 1989;5: Isenmann R, Rau B, Beger HG: Bacterial infection and extent of necrosis are determinants of organ failure in patients with acute necrotizing pancreatitis. Br J Surg 1999;86: Gloor B, Müller CA, Worni M, Martignoni ME, Uhl W, Büchler MW: Late mortality in patients with severe acute pancreatitis. Br J Surg 2001;88: Le Mee J, Paye F, Sauvanet A, et al: Incidence and reversibility of organ failure in the course of sterile or infected necrotizing pancreatitis. Arch Surg 2001;136: Ho HS, Frey CF: The role of antibiotic prophylaxis in severe acute pancreatitis. Arch Surg 1997;132: Pederzoli P, Bassi C, Vesentini S, Campedelli A: A randomized multicenter clinical trial of antibiotic prophylaxis of septic complications in acute necrotizing pancreatitis with imipenem. Surg Gynecol Obstet 1993;176: Delcenserie R, Yzet T, Ducroix JP: Prophylactic antibiotics in treatment of severe acute alcoholic pancreatitis. Pancreas 1996;13: Nordback I, Sand J, Saaristo R, Paajanen H: Early treatment with antibiotics reduces the need for surgery in acute necrotizing pancreatitis A single-center randomized study. J Gastrointest Surg 2001;5: Sainio V, Kemppainen E, Puolakkainen P, et al: Early antibiotic treatment in acute necrotising pancreatitis. Lancet 1995;346: Golub R, Siddiqi F, Pohl D: Role of antibiotics in acute pancreatitis: A meta-analysis. J Gastrointest Surg 1998;2: Sharma VK, Howden CW: Prophylactic antibiotic administration reduces sepsis and mortality in acute necrotizing pancreatitis: a metaanalysis. Pancreas 2001;22: Banks PA, Gerzof SG, Langevin RE, Silverman SG, Sica GT, Hughes MD: CT-guided aspiration of suspected pancreatic infection: bacteriology and clinical outcome. Int J Pancreatol 1995;18: Hiatt JR, Fink AS, King W, Pitt HA: Percutaneous aspiration of peripancreatic fluid collections: A safe method to detect infection. Surgery 1987;101: Evans WK, Ho CS, McLoughlin MJ, Tao LC: Fatal necrotizing pancreatitis following fineneedle aspiration biopsy of the pancreas. Radiology 1981;141: Levin DP, Bret PM: Percutaneous fine-needle aspiration biopsy of the pancreas resulting in death. Gastrointest Radiol 1991;16: Rau B, Pralle U, Mayer JM, Beger HG: Role of ultrasonographically guided fine-needle aspiration cytology in the diagnosis of infected pancreatic necrosis. Br J Surg 1998;85: Bradley EL: A fifteen year experience with open drainage for infected pancreatic necrosis. Surg Gynecol Obstet 1993;177: Sarr MG, Nagorney DM, Mucha PJ, Farnell MB, Johnson CD: Acute necrotizing pancreatitis: Management by planned, staged pancreatic necrosectomy/debridement and delayed primary wound closure over drains. Br J Surg 1991;78: Bittner R, Block S, Büchler M, Beger HG: Pancreatic abscess and infected pancreatic necrosis. Different local septic complications in acute pancreatitis. Dig Dis Sci 1987;32: Widdison AL, Karanjia ND: Pancreatic infection complicating acute pancreatitis. Br J Surg 1993;80: Bradley EL, Allen K: A prospective longitudinal study of observation versus surgical intervention in the management of necrotizing pancreatitis. Am J Surg 1991;161: Fernandez-del Castillo C, Rattner DW, Makary MA, Mostafavi A, McGrath D, Warshaw AL: Debridement and closed packing for the treatment of necrotizing pancreatitis. Ann Surg 1998;228: Karimgani I, Porter KA, Langevin RE, Banks PA: Prognostic factors in sterile pancreatic necrosis. Gastroenterology 1992;103: Beger HG, Büchler M, Bittner R, Block S, Nevalainen T, Roscher R: Necrosectomy and postoperative local lavage in necrotizing pancreatitis. Br J Surg 1988;75: Rau B, Pralle U, Uhl W, Schoenberg MH, Beger HG: Management of sterile necrosis in instances of severe acute pancreatitis. J Am Coll Surg 1995;181: Rattner DW, Legermate DA, Lee MJ, Mueller PR, Warshaw AL: Early surgical debridement of symptomatic pancreatic necrosis is beneficial irrespective of infection. Am J Surg 1992; 163: Tsiotos GG, Luque-de LE, Soreide JA, et al: Management of necrotizing pancreatitis by repeated operative necrosectomy using a zipper technique. Am J Surg 1998;175: Kivilaakso E, Fraki O, Nikki P, Lempinen M: Resection of the pancreas for acute fulminant pancreatitis. Surg Gynecol Obstet 1981;152: Hartwig W, Maksan SM, Foitzik T, Schmidt J, Herfarth C, Klar E: Reduction in mortality with delayed surgical therapy of severe pancreatitis. J Gastrointest Surg 2002;6: Fernandez-Cruz L, Navarro S, Valderrama R, et al: Acute necrotizing pancreatitis: A multicenter study. Hepatogastroenterology 1994;41: Mier J, Leon EL, Castillo A, Robledo F, Blanco R: Early versus late necrosectomy in severe necrotizing pancreatitis. Am J Surg 1997;173: Alexandre JH, Guerrieri MT: Role of total pancreatectomy in the treatment of necrotizing pancreatitis. World J Surg 1981;5: Edelmann G, Boutelier P: Treatment of acute necrotizing pancreatitis through the early surgical ablation of necrotic portions. Chirurgie 1974;100: Nordback IH, Auvinen OA: Long-term results after pancreas resection for acute necrotizing pancreatitis. Br J Surg 1985;72: Larvin M, Chalmers AG, Robinson PJ, McMahon MJ: Debridement and closed cavity irrigation for the treatment of pancreatic necrosis. Br J Surg 1989;76: Bradley EL: Management of infected pancreatic necrosis by open drainage. Ann Surg 1987; 206: Baron TH, Thaggard WG, Morgan DE, Stanley RJ: Endoscopic therapy for organized pancreatic necrosis. Gastroenterology 1996;111: Freeny PC, Hauptmann E, Althaus SJ, Traverso LW, Sinanan M: Percutaneous CT-guided catheter drainage of infected acute necrotizing pancreatitis: Techniques and results. Am J Roentgenol 1998;170: Baril NB, Ralls PW, Wren SM, et al: Does an infected peripancreatic fluid collection or abscess mandate operation? Ann Surg 2000;231: Carter CR, McKay CJ, Imrie CW: Percutaneous necrosectomy and sinus tract endoscopy in the management of infected pancreatic necrosis: an initial experience. Ann Surg 2000; 232: Winslet MC, Imray C, Neoptolemos JP: Biliary acute pancreatitis. Hepatogastroenterology 1991;38: Acosta JM, Ledesma CL: Gallstone migration as a cause of acute pancreatitis. N Engl J Med 1974;290: Neoptolemos JP, Carr-Locke DL, London N, Bailey I, Fossard DP: ERCP findings and the role of endoscopic sphincterotomy in acute gallstone pancreatitis. Br J Surg 1988;75: Pancreatology 2002;2: Uhl et al.

9 61 Rünzi M, Saluja A, Lerch MM, Dawra R, Nishino H, Steer ML: Early ductal decompression prevents the progression of biliary pancreatitis: An experimental study in the opossum. Gastroenterology 1993;105: Neoptolemos JP, Carr-Locke DL, London NJ, Bailey IA, James D, Fossard DP: Controlled trial of urgent endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy versus conservative treatment for acute pancreatitis due to gallstones. Lancet 1988; ii: Fan ST, Lai EC, Mok FP, Lo CM, Zheng SS, Wong J: Early treatment of acute biliary pancreatitis by endoscopic papillotomy. N Engl J Med 1993;328: Fölsch UR, Nitsche R, Ludtke R, Hilgers RA, Creutzfeldt W: Early ERCP and papillotomy compared with conservative treatment for acute biliary pancreatitis. The German Study Group on Acute Biliary Pancreatitis. N Engl J Med 1997;336: Liu CL, Lo CM, Fan ST: Acute biliary pancreatitis: Diagnosis and management. World J Surg 1997;21: Steinberg WM, Neoptolemos JP, Fölsch UR, Layer P: Controversies in clinical pancreatology. The management of severe gallstone pancreatitis. Pancreas 2001;22: Fölsch UR, Neoptolemos J: The management of severe gallstone pancreatitis. Pancreas 2002; 24: Kelly TR, Wagner DS: Gallstone pancreatitis: A prospective randomized trial of the timing of surgery. Surgery 1988;104: Neoptolemos JP, Shaw DE, Carr-Locke DL: A multivariate analysis of preoperative risk factors in patients with common bile duct stones. Implications for treatment. Ann Surg 1989; 209: Davidson BR, Neoptolemos JP, Carr-Locke DL: Endoscopic sphincterotomy for common bile duct calculi in patients with gall bladder in situ considered unfit for surgery. Gut 1988;29: Hammarstrom LE, Holmin T, Stridbeck H: Endoscopic treatment of bile duct calculi in patients with gallbladder in situ: Long-term outcome and factors. Scand J Gastroenterol 1996;31: Hill J, Martin DF, Tweedle DE: Risks of leaving the gallbladder in situ after endoscopic sphincterotomy for bile duct stones. Br J Surg 1991;78: Keulemans YC, Rauws EA, Huibregtse K, Gouma DJ: Current management of the gallbladder after endoscopic sphincterotomy for common bile duct stones. Gastrointest Endosc 1997;46: Poon RT, Liu CL, Lo CM, et al: Management of gallstone cholangitis in the era of laparoscopic cholecystectomy. Arch Surg 2001;136: Dixon JA, Hillam JD: Surgical treatment of biliary tract disease associated with acute pancreatitis. Am J Surg 1970;120: Frei GJ, Frei VT, Thirlby RC, McClelland RN: Biliary pancreatitis: Clinical presentation and surgical management. Am J Surg 1986;151: Ranson JH: The timing of biliary surgery in acute pancreatitis. Ann Surg 1979;189: Pellegrini CA: Surgery for gallstone pancreatitis. Am J Surg 1993;165: Uhl W, Müller CA, Krahenbuhl L, Schmid SW, Scholzel S, Büchler MW: Acute gallstone pancreatitis: Timing of laparoscopic cholecystectomy in mild and severe disease. Surg Endosc 1999;13: Tang E, Stain SC, Tang G, Froes E, Berne TV: Timing of laparoscopic surgery in gallstone pancreatitis. Arch Surg 1995;130: Tondelli P, Stutz K, Harder F, Schuppisser JP, Allgower M: Acute gallstone pancreatitis: Best timing for biliary surgery. Br J Surg 1982;69: Runkel NS, Buhr HJ, Herfarth C: Outcome after surgery for biliary pancreatitis. Eur J Surg 1996;162: Soper NJ, Brunt LM, Callery MP, Edmundowicz SA, Aliperti G: Role of laparoscopic cholecystectomy in the management of acute gallstone pancreatitis. Am J Surg 1994;167: Shemesh E, Czerniak A, Schneabaum S, Nass S: Early endoscopic sphincterotomy in the management of acute gallstone pancreatitis in elderly patients. J Am Geriatr Soc 1990;38: Uomo G, Manes G, Laccetti M, Cavallera A, Rabitti PG: Endoscopic sphincterotomy and recurrence of acute pancreatitis in gallstone patients considered unfit for surgery. Pancreas 1997;14: Welbourn CR, Beckly DE, Eyre-Brook IA: Endoscopic sphincterotomy without cholecystectomy for gall stone pancreatitis. Gut 1995;37: Pancreatology 2002;2: