- Email: [email protected]
Management of Infected Necrosis Secondary to Acute Pancreatitis: A Balanced Role for Minimal Access Techniques
IAP Guidelines: Related Paper Pancreatology 2003;3:133–138 DOI: 10.1159/000070081
Management of Infected Necrosis Secondary to Acute Pancreatitis: A Balanced Role for Minimal Access Techniques Ross Carter West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK
Key Words Percutaneous necrosectomy W Minimal access techniques W Multimodal strategy
Acute pancreatitis varies from a mild and rapidly resolving attack (80%) requiring little more than analgesia and a short period of intravenous fluid resuscitation, to a severe life-threatening illness. Patients have been traditionally classified [1] as having either mild or severe acute pancreatitis (when the illness is associated with organ failure and/or local complications, e.g. necrosis, pseudocyst or abscess), although in truth a spectrum of clinical behavior exists. We have recently highlighted the dynamic pattern of pancreatitis-associated organ failure [2]. Various clinical and biochemical scoring systems [3, 4] have been used in an attempt to clinically differentiate between mild and severe disease; however, in practice, rather than being ‘prediction’ systems, these in truth record the degree of developing or established organ dysfunction. Most often this is an expression of the coincident development of pancreatic necrosis, although patients with oedematous pancreatitis may manifest clinical features of a severe attack. The majority of patients with acute pancreatitis rapidly resolve, the major issue being the prevention of further attacks by expedient cholecystectomy or endoscopic sphincterotomy. Of those with the severe form of the dis-
ABC
© 2003 S. Karger AG, Basel and IAP 1424–3903/03/0032–0133$19.50/0
Fax + 41 61 306 12 34 E-Mail [email protected] www.karger.com
Accessible online at: www.karger.com/pan
ease, most have evidence of organ failure at the time of admission or very shortly thereafter. It is exceptional for a patient to have no evidence of organ failure in the first week of illness and to subsequently develop a significant later local complication. Furthermore, the majority of patients with severe early organ dysfunction will have pancreatic necrosis on CT scan. Unfortunately, although over 50% of the mortality associated with severe acute pancreatitis occurs within the first week [5, 6], early surgical intervention for necrosis has little role in these patients [7], and treatment involves maximal supportive care. Gloor et al. [8] have disputed the high incidence of early death, which is an indication of the differing referral patterns to specialized units. Late deterioration of organ dysfunction occurs most commonly in the 2nd to 3rd week after admission [9], and is usually the result of secondary infection of the pancreatic or peri-pancreatic necrosis. The mode of death in patients with infected pancreatic necrosis is again multiple organ failure, thought to be a consequence of excessive or unregulated activation of the inflammatory cascade. There is therefore a bimodal pattern of mortality, with an early peak from overwhelming organ failure in the first week and a second peak of organ dysfunction, associated with the development of secondary septic complications a few weeks into the illness [2], and this pattern is consistent throughout the randomised studies [10] of early pharmacological intervention in acute pancreatitis.
Mr. Ross Carter Department of Upper GI and Pancreaticobiliary Surgery Glasgow Royal Infirmary Glasgow G31 2ER (UK) Tel. +44 141 211 5129, Fax +44 141 211 4997, E-Mail [email protected]
Factors Affecting the Outcome following Surgical Intervention
Sterile necrosis can usually be successfully treated by an initially conservative approach [11], although surgery may be required for late complications, such as pseudocyst or duct disruption. By contrast, there is general consensus that infected necrosis is an indication for intervention, as without drainage, mortality approaches 100% [12–14], although recently, case reports of successful conservative treatment have emerged. Fifty years ago, surgical exploration in severe acute pancreatitis was almost universally fatal [15]. Until the 1970s, standard management of this condition often involved partial or total resective procedures but was associated with a mortality often in excess of 50% [16]. Although the presence of intra-peritoneal fluid is not uncommon, peritoneal lavage/dialysis has been shown to be of no benefit as this fails to address the retroperitoneal origin of the inflammatory process [17]. Appropriate management of septic complications can influence outcome, and therefore the early recognition of infection and deteriorating organ function has become central to the management of these patients. In addition, delay in intervention results in higher mortality once infection occurs [18]. However, all patients with necrotising pancreatitis exhibit a systemic inflammatory response, and this can often be misinterpreted as evidence of secondary infection. Even proven bacteraemic episodes may be secondary to line sepsis rather than infection of the necrotic pancreatic or peri-pancreatic tissue. The preoperative identification of pancreatic sepsis therefore requires CT evidence of retroperitoneal gas or fine-needle aspiration (FNA) sampling of the necrotic material [19]. The evolution of pancreatic and peri-pancreatic necrosis is probably complete within the first few days of the illness; however, it takes several weeks for full separation of the vital and devitalized tissue to be completed, with formation of a ‘sequestrum’ within the retroperitoneum. Early surgical intervention therefore requires more of a resective procedure than simple debridement, and is associated with increased mortality. The ease of debridement increases with time, and proponents of the use of prophylactic antibiotics have suggested that whilst they may not affect intervention rates, they may delay the requirement for intervention to allow more complete separation to occur. The mortality associated with surgery is also intimately related to the presence or absence of organ failure. The degree of this organ dysfunction is not directly related to
134
Pancreatology 2003;3:133–138
the extent of pancreatic or peri-pancreatic necrosis, or even the presence of infection, although an association exists [20]. Background co-morbidity and genetic predisposition both play a significant role [21]. The precise mechanism of the initiation of organ dysfunction is unknown; however, the absence of organ dysfunction in the preoperative patient is the single most accurate determinant of ultimate survival. Whilst the indication for surgery has usually been the identification of bacteria on FNA, the outcome from intervention is very different at 3 rather than 7 weeks; with total rather than minimal necrosis; or in patients with, rather than without, organ dysfunction. Timing of intervention is particularly important when assessing results of intervention. Patients with a localised retrogastric pseudocyst associated with significant necrosis or a localised abscess due to a late infection of a pseudocyst, requiring intervention more than 4 weeks from the initial presentation, rarely have organ failure, and any technique resulting in adequate drainage/debridement will be associated with good results. These patients may be effectively treated by an open or laparoscopic cystgastrostomy, draining the cyst into the back wall of the stomach and performing simultaneous surgical debridement of any necrotic tissue within the cavity. Patients presenting with sepsis within the first 4 weeks require a different strategy. Separation of the devitalised tissue is incomplete and the cavity wall immature. A series of surgical approaches have been described in the last 20 years; all of these recognised the fundamental importance of addressing the solid necrotic component within the infected cavity, with differing approaches to the post-operative management of the necrosectomy cavity. Necrosectomy with post-operative cavity tube drainage was associated with an improved outcome compared to resective procedures or simple peritoneal lavage [22], but the requirements for repeated surgical intervention remained, mainly due to recurrent sepsis. This led to the development of techniques such as open packing [23] or the utilisation of prolonged post-operative cavity lavage [24]. Debridement followed by closure over drains was described by Warshaw and Jin [22] in 1985, and their results were updated in 1999. In the later paper, they described a series of 64 patients, of whom 36 had infected necrosis. Only 31% had organ failure. Overall mortality was only 6.2% and the outcome appeared to be unrelated to the presence of infection. Bradley [23] described the technique of ‘open packing’, using lubricated gauze swabs to pack the surgical cavity following necrosectomy in 28 patients with infected ne-
Carter
Fig. 1. Percutaneous necrosectomy: nephroscope access to necrosis using a 34-FG Amplatz sheath.
crosis, and reported a mortality of 11%. More recently, in 1998, a Dutch group [25] reported their results using this technique in 27 patients with necrotising pancreatitis, with major complications in 14, recurrent abscesses in 9 and a mortality rate of 39%. In contrast, Branum et al. [26] reported a 12% mortality rate with a similar approach in 50 patients, of whom 84% had infected necrosis. Perhaps the most commonly adopted approach is that of closed lavage of the debrided cavity, first described by Beger et al. [27] in 1982, where they reported their experience in treating 118 patients with pancreatic necrosis, only some of whom were infected. Overall mortality was 33%. Several subsequent reports from the same group have reported mortality rates from infected necrosis of 32.1% [28], 37.8% [9] and 25.2% [20]. Büchler et al. [29] reported a mortality of 24% using this technique; however, the most impressive figures were reported by Farkas et al. [30], with an overall hospital mortality of 7% in 123 patients with infected necrosis. The differing success reported by groups using apparently similar approaches illustrates the difficulties in comparing different or evolving techniques performed around the world. Most techniques have an average mortality rate of between 20 and 25%; however, the mortality in patients with established multiple organ failure may exceed 75%. Open surgical approaches are associated with a universal initial post-operative deterioration, which many patients who require cardio-respiratory and renal support pre-operatively do not survive. The almost prohibitory
mortality has led to the development of minimally invasive procedures in an attempt to address the specific problems of this small subgroup of high-risk patients. Perhaps the simplest approach to reducing the surgical insult is to reduce the size of the incision. Fagniez et al. [31] described a lateral (retroperitoneal) technique utilising a limited loin/subcostal, retrocolic approach for debridement of pancreatic and peri-pancreatic necrosis. The technique was, however, associated with major morbidity (enteric fistula 45%, haemorrhage 40% and colonic necrosis 15%), and has not gained popularity. The Leeds group has confirmed the feasibility of a formal laparoscopic necrosectomy. The technical laparoscopic expertise required has limited its more widespread adoption, but the results of their series are awaited with interest. Developments in interventional radiology have revolutionized the management of many surgical conditions; however, in the presence of pancreatic necrosis, simple aspiration and percutaneous drainage alone rarely result in resolution in that they do not address the solid component within the abscess, and should therefore be discouraged as sole treatment. They may have a role as a temporising measure in the hope of finding a ‘window of opportunity’ in which to perform definitive intervention. The radiological approach was taken to its limits by Freeny et al. [32], who combined aggressive CT-guided percutaneous drainage with continuous post-drainage lavage and showed that the pancreatic sepsis may resolve; however, nearly three quarters of the patients will subsequently require surgical intervention. The logistic demands on the
Minimally Invasive Pancreatic Necrosectomy
Pancreatology 2003;3:133–138
135
radiological department of this approach have lessened its universal appeal. In 1996, Baron et al. [33] described a variation on this approach, combining endoscopic cystgastrostomy with naso-cyst lavage, and reported good results in an initial series of eleven patients. Three quarters of their patients had pseudocysts rather than abscesses (only 28% were infected at the time of drainage), at a median of 7 weeks following the onset of their illness. It is worthy of note that up to 60% of those patients successfully drained developed further collections in the subsequent 2 years [34]. This series confirmed that in the presence of necrosis, therefore, drainage must be combined with some form of surgical removal of the necrotic material. This technique has been further refined and significant tract dilatation is possible endoscopically, allowing limited debridement of necrosis. In 2000, we described [35] our technique of percutaneous necrosectomy involving intraoperative dilatation of a percutaneous drain tract, and subsequent necrosectomy using a urological rigid rod lens system, usually from the left flank or a right subcostal approach. To avoid contamination by bowel puncture, double-contrast CTguided FNA is performed. Our preferred route is through the left fat plane between the spleen posteriorly and the colon anteriorly, although for right-sided collections, access can usually be obtained anterior to the duodenum, between colon and liver. The tract is first dilated using a balloon dilator, allowing insertion of a 34-FG Amplatz sheath. Initial intermittent copious lavage and suction is performed until the irrigant clears sufficiently to be able to see within the cavity. Devitalised tissue is easily identified and can be removed by gentle traction in a piecemeal fashion. Experience has suggested that overzealous attempts at cavity clearance are unnecessary and can lead to bleeding. An 8-FG umbilical catheter sutured to a 28-FG tube drain is then passed to the far end of the cavity to allow continuous post-operative lavage (500 ml/h, Dianil 7) via the umbilical catheter. Planned second-look procedures are then performed every 7–10 days, until the cavity is clean. Most centres have reported the results of a consistent method of treatment, comparing their results to those of other centres, where referral practice, selection criteria, background morbidity and therefore outcome may differ considerably. We have now treated over 35 patients using this technique. We have reported our initial experience [35]; however, we wish to reserve our conclusions on efficacy until we have treated an appropriately large series of patients, so that we may compare these with our patients
136
Pancreatology 2003;3:133–138
managed by traditional open techniques. Early observations have shown a reduction in the almost universal deterioration in organ function following an open approach, and therefore a significant reduction in the need for postoperative intensive care management. Whether this is extrapolated into a reduction in mortality remains unanswered. The preliminary results have been encouraging; however, ongoing assessment of this approach continues.
Minimal Access Surgical Intervention
The disappointingly high mortality associated with infected necrosis in 2002, despite advances in critical care support and the variety of possible surgical, endoscopic and radiological approaches, is an indication that no single technique provides an answer. Within the surgical literature, it is impossible to determine the hidden effects of factors such as referral pattern, patient selection, pre-surgical percutaneous management and population morbidity. Improvements in outcome over historical controls also have to be considered against a background of simultaneous advances in general intensive care patient management. Indications for necrosectomy also vary widely, and authors have tended to combine management of late abscesses with cases of true infected necrosis. Individual surgical units have tended, probably inappropriately, to consider their own surgical approach to this complex group of patients as a panacea, comparing results to historical controls or with other reported series. Background morbidity of patients within a series is difficult to determine and undoubtedly has a major influence on outcome. Half of those patients dying as a result of severe acute pancreatitis do so within the first few days of the illness, and may never reach a specialised unit, whilst others may not be considered fit for intervention. As the reported mortality relates only to the surgically treated patients rather than the background denominator group, series may underestimate mortality. Small numbers in reports also result in differing rates from individual centres over time. Referral patterns, co-morbidity and selection criteria therefore may be some of the reasons why clinicians have struggled to emulate in practice some of the mortality rates reported in the literature [30]. For most major centres, overall mortality remains between 20 and 25%, and is significantly higher in the high-risk group with established multiple organ failure. The relative infrequency of patients requiring intervention results in most surgeons adopting a favoured, but consistent, approach to infected necrosis. Within special-
Carter
ized units, it has become increasingly obvious that not all patients respond equally to a given surgical stimulus. Those patients with infected necrosis but without significant organ dysfunction will generally do well regardless of the approach chosen. In these patients, an aggressive surgical approach will address the sepsis, eliminate the necrosis and potentially result in a more rapid recovery. In patients at the severe end of the disease spectrum with established organ dysfunction, traditional intervention is associated with significant mortality, and these patients may benefit from a more flexible approach to the control of sepsis. It may be through utilizing a minimal access technique that improvements in outcome may be achieved. Undoubtedly, the severity of systemic sepsis and organ dysfunction can be reduced by percutaneous or endoscopic drainage; however, the improvement tends to be temporary unless drainage is maintained through some means of addressing the solid component of these abscesses. Tract dilatation and minimally invasive necrosectomy achieves drainage and addresses the solid component, whilst minimizing the surgical insult to the patient. No randomised studies exist comparing one management technique with another. All studies have tended to involve small numbers of patients and have reported a retrospective review of results. Patient selection criteria and patient comorbidity vary enormously. Consequently, it is impossible to draw firm conclusions from the literature, apart from the fact that regardless of the approach
adopted, mortality remains high. The traditional approach has been to compare the results of different techniques of open or minimally invasive necrosectomy. This represents an over-simplification of the clinical complexity posed by these patients, and improvements in outcome are more likely to be achieved through utilisation of a variety of techniques rather than the universal adoption of a single surgical method. We first performed a percutaneous necrosectomy out of necessity in a patient who was otherwise being considered for withdrawal of treatment. Latterly, we continued our series in order to confirm the feasibility of the technique and to address some of the practical issues raised. From our pilot data, our overall results appear at least as good as our historical controls; however, in future we may well limit the use of this approach to specific indications, or as part of a multimodality strategy in critically ill patients. The specific role of percutaneous necrosectomy remains to be clarified; however, the debate should not be about which technique is best, but rather which of the many surgical options most closely addresses the complex needs of the individual patient.
Acknowledgements I would like to acknowledge the contribution of my colleagues Mr. Colin McKay, Professor Clem Imrie and the members of the West of Scotland Pancreatic Research Unit to this work.
References 1 Bradley EL III: A clinically based classification system for acute pancreatitis. Summary of the International Symposium on Acute Pancreatitis, Atlanta, Ga, September 11 through 13, 1992. Arch Surg 1993;128:586–590. 2 Buter A, Imrie CW, Carter CR, Evans S, McKay CJ: Dynamic nature of early organ dysfunction determines outcome in acute pancreatitis. Br J Surg 2002;89:298–302. 3 McKay CJ, Imrie CW: Staging of acute pancreatitis: Is it important? Surg Clin North Am 1999;79:733–743. 4 Larvin M, McMahon MJ: APACHE-II score for assessment and monitoring of acute pancreatitis. Lancet 1989;ii:201–205. 5 McKay CJ, Evans S, Sinclair M, Carter CR, Imrie CW: High early mortality rate from acute pancreatitis in Scotland, 1984–1995. Br J Surg 1999;86:1302–1305. 6 Mutinga M, Rosenbluth A, Tenner SM, Odze RR, Sica GT, Banks PA: Does mortality occur early or late in acute pancreatitis? Int J Pancreatol 2000;28:91–95.
Minimally Invasive Pancreatic Necrosectomy
7 Meir J, Luque-de Leon E, Castillo A, Robledo F, Blanco R: Early versus late necrosectomy in severe necrotising pancreatitis. Am J Surg 1997;173:71–75. 8 Gloor B, Müller CA, Worni M, Martignoni ME, Uhl W, Büchler MW: Late mortality in patients with severe acute pancreatitis. Br J Surg 2001;88:975–979. 9 Beger HG, Bittner R, Block S, Büchler M: Bacterial contamination of pancreatic necrosis. A prospective clinical study. Gastroenterology 1986;91:433–438. 10 Johnson CD, Kingsnorth AN, Imrie CW, McMahon MJ, Neoptolemos JP, McKay C, Toh SK, Skaife P, Leeder PC, Wilson P, Larvin M, Curtis LD: Double blind, randomised, placebo controlled study of a platelet activating factor antagonist, lexipafant, in the treatment and prevention of organ failure in predicted severe acute pancreatitis. Gut 2001;48:62–69. 11 Bradley EL III, Allen K: A prospective longitudinal study of observation versus surgical intervention in the management of necrotizing pancreatitis. Am J Surg 1991;161:19–25.
12 Beger HG, Rau B, Mayer J, Isenmann R: Surgical treatment of acute pancreatitis; in Lankisch PG, DiMagno EP (eds): Pancreatic Disease: State of the Art and Future Aspects of Research. New York, Springer, 1999, pp 78–89. 13 Gloor B, Uhl W, Müller CA, Büchler MW: The role of surgery in the management of acute pancreatitis. Can J Gastroenterol 2000; 14(suppl D):136D–140D. 14 Buchler P, Reber HA: Surgical approach in patients with acute pancreatitis. Is infected or sterile necrosis an indication – in whom should this be done, when, and why? Gastroenterol Clin North Am 1999;28:661–671. 15 Moynihan B: Acute pancreatitis. Ann Surg 1925;81:132–142. 16 Hollender LF, Meyer C, Keller D: Planned operations for necrotising pancreatitis: The continental experience; in Howard JM, Jordan GL Jr, Reber HA (eds): Surgical Diseases of the Pancreas. Philadelphia, Lea and Febiger, 1986, pp 450–460.
Pancreatology 2003;3:133–138
137
17 Mayer AD, McMahon MJ, Corfield AP: Controlled clinical trial of peritoneal lavage for the treatment of severe acute pancreatitis. N Engl J Med 1985;312:399–404. 18 De Beaux AC, Palmer KR, Carter DC: Factors influencing morbidity and mortality in acute pancreatitis; an analysis of 279 cases. Gut 1995;37:121–126. 19 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;85:179–184. 20 Isenmann R, Beger HG: Natural history of acute pancreatitis and the role of infection. Baillière’s Best Pract Res Clin Gastroenterol 1999;13:291–301. 21 Buter A, Eskdale J, Gallagher G, Robertson S, Evans S, Carter CR, Imrie CW, McKay CJ: The IL-10.R3 microsatellite allele is associated with fulminant early organ dysfunction in acute pancreatitis (abstract). Pancreas 1999;19: 417. 22 Warshaw AL, Jin G: Improved survival in 45 patients with pancreatic abscess. Ann Surg 1985;202:408–415. 23 Bradley EL III: Open packing in infected pancreatic necrosis. Dig Surg 1997;14:77–81.
138
24 Rau B, Beger HG: Necrosectomy and closed irrigation for necrotizing pancreatitis. Probl Gen Surg 1996;13:137–145. 25 Bosscha K, Hulstaert PF, Hennipman A, Visser MR, Gooszen HG, van Vroonhoven TJ, v d Werken C: Fulminant acute pancreatitis and infected necrosis: Results of open management of the abdomen and ‘planned’ reoperations. J Am Coll Surg 1998;187:255–262. 26 Branum G, Galloway J, Hirchowitz W, Fendley M, Hunter J: Pancreatic necrosis: Results of necrosectomy, packing, and ultimate closure over drains. Ann Surg 1998;277:870–877. 27 Beger HG, Krautzberger W, Bittner R, Block S: Necrotizing pancreatitis. Indication for operation and results in 118 patients (in German). Chirurg 1982;53:784–789. 28 Beger HG, Krautzberger W, Bittner R: Results of surgical treatment of necrotizing pancreatitis. World J Surg 1985;9:972–979. 29 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;232:619–626.
Pancreatology 2003;3:133–138
30 Farkas G, Marton J, Mandi Y, Szederkenyi E: Surgical strategy and management of infected pancreatic necrosis. Br J Surg 1996;83:930– 933. 31 Fagniez PL, Rotman N, Kracht M: Direct retroperitoneal approach to necrosis in severe acute pancreatitis. Br J Surg 1989;76:264–267. 32 Freeny PC, Hauptmann E, Althaus SJ, Traverso LW, Sinanan M: Percutaneous CT-guided catheter drainage of infected acute necrotizing pancreatitis: Technique and results. AJR Am J Roentgenol 1998;170:969–975. 33 Baron TH, Thaggard WG, Morgan DE, Stanley RJ: Endoscopic therapy for organized pancreatic necrosis. Gastroenterology 1996;111: 755–764. 34 Adkisson KW, Morgan DE, Baron TH: Long term outcome following successful endoscopic drainage of organised pancreatic necrosis (OPN): Skunkpoking revisited (abstract). Gastrointest Endosc 1997;45:514. 35 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; 232:175–180.
Carter
Management of Infected Necrosis Secondary to Acute Pancreatitis: A Balanced Role for Minimal Access Techniques Ross Carter West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK
Key Words Percutaneous necrosectomy W Minimal access techniques W Multimodal strategy
Acute pancreatitis varies from a mild and rapidly resolving attack (80%) requiring little more than analgesia and a short period of intravenous fluid resuscitation, to a severe life-threatening illness. Patients have been traditionally classified [1] as having either mild or severe acute pancreatitis (when the illness is associated with organ failure and/or local complications, e.g. necrosis, pseudocyst or abscess), although in truth a spectrum of clinical behavior exists. We have recently highlighted the dynamic pattern of pancreatitis-associated organ failure [2]. Various clinical and biochemical scoring systems [3, 4] have been used in an attempt to clinically differentiate between mild and severe disease; however, in practice, rather than being ‘prediction’ systems, these in truth record the degree of developing or established organ dysfunction. Most often this is an expression of the coincident development of pancreatic necrosis, although patients with oedematous pancreatitis may manifest clinical features of a severe attack. The majority of patients with acute pancreatitis rapidly resolve, the major issue being the prevention of further attacks by expedient cholecystectomy or endoscopic sphincterotomy. Of those with the severe form of the dis-
ABC
© 2003 S. Karger AG, Basel and IAP 1424–3903/03/0032–0133$19.50/0
Fax + 41 61 306 12 34 E-Mail [email protected] www.karger.com
Accessible online at: www.karger.com/pan
ease, most have evidence of organ failure at the time of admission or very shortly thereafter. It is exceptional for a patient to have no evidence of organ failure in the first week of illness and to subsequently develop a significant later local complication. Furthermore, the majority of patients with severe early organ dysfunction will have pancreatic necrosis on CT scan. Unfortunately, although over 50% of the mortality associated with severe acute pancreatitis occurs within the first week [5, 6], early surgical intervention for necrosis has little role in these patients [7], and treatment involves maximal supportive care. Gloor et al. [8] have disputed the high incidence of early death, which is an indication of the differing referral patterns to specialized units. Late deterioration of organ dysfunction occurs most commonly in the 2nd to 3rd week after admission [9], and is usually the result of secondary infection of the pancreatic or peri-pancreatic necrosis. The mode of death in patients with infected pancreatic necrosis is again multiple organ failure, thought to be a consequence of excessive or unregulated activation of the inflammatory cascade. There is therefore a bimodal pattern of mortality, with an early peak from overwhelming organ failure in the first week and a second peak of organ dysfunction, associated with the development of secondary septic complications a few weeks into the illness [2], and this pattern is consistent throughout the randomised studies [10] of early pharmacological intervention in acute pancreatitis.
Mr. Ross Carter Department of Upper GI and Pancreaticobiliary Surgery Glasgow Royal Infirmary Glasgow G31 2ER (UK) Tel. +44 141 211 5129, Fax +44 141 211 4997, E-Mail [email protected]
Factors Affecting the Outcome following Surgical Intervention
Sterile necrosis can usually be successfully treated by an initially conservative approach [11], although surgery may be required for late complications, such as pseudocyst or duct disruption. By contrast, there is general consensus that infected necrosis is an indication for intervention, as without drainage, mortality approaches 100% [12–14], although recently, case reports of successful conservative treatment have emerged. Fifty years ago, surgical exploration in severe acute pancreatitis was almost universally fatal [15]. Until the 1970s, standard management of this condition often involved partial or total resective procedures but was associated with a mortality often in excess of 50% [16]. Although the presence of intra-peritoneal fluid is not uncommon, peritoneal lavage/dialysis has been shown to be of no benefit as this fails to address the retroperitoneal origin of the inflammatory process [17]. Appropriate management of septic complications can influence outcome, and therefore the early recognition of infection and deteriorating organ function has become central to the management of these patients. In addition, delay in intervention results in higher mortality once infection occurs [18]. However, all patients with necrotising pancreatitis exhibit a systemic inflammatory response, and this can often be misinterpreted as evidence of secondary infection. Even proven bacteraemic episodes may be secondary to line sepsis rather than infection of the necrotic pancreatic or peri-pancreatic tissue. The preoperative identification of pancreatic sepsis therefore requires CT evidence of retroperitoneal gas or fine-needle aspiration (FNA) sampling of the necrotic material [19]. The evolution of pancreatic and peri-pancreatic necrosis is probably complete within the first few days of the illness; however, it takes several weeks for full separation of the vital and devitalized tissue to be completed, with formation of a ‘sequestrum’ within the retroperitoneum. Early surgical intervention therefore requires more of a resective procedure than simple debridement, and is associated with increased mortality. The ease of debridement increases with time, and proponents of the use of prophylactic antibiotics have suggested that whilst they may not affect intervention rates, they may delay the requirement for intervention to allow more complete separation to occur. The mortality associated with surgery is also intimately related to the presence or absence of organ failure. The degree of this organ dysfunction is not directly related to
134
Pancreatology 2003;3:133–138
the extent of pancreatic or peri-pancreatic necrosis, or even the presence of infection, although an association exists [20]. Background co-morbidity and genetic predisposition both play a significant role [21]. The precise mechanism of the initiation of organ dysfunction is unknown; however, the absence of organ dysfunction in the preoperative patient is the single most accurate determinant of ultimate survival. Whilst the indication for surgery has usually been the identification of bacteria on FNA, the outcome from intervention is very different at 3 rather than 7 weeks; with total rather than minimal necrosis; or in patients with, rather than without, organ dysfunction. Timing of intervention is particularly important when assessing results of intervention. Patients with a localised retrogastric pseudocyst associated with significant necrosis or a localised abscess due to a late infection of a pseudocyst, requiring intervention more than 4 weeks from the initial presentation, rarely have organ failure, and any technique resulting in adequate drainage/debridement will be associated with good results. These patients may be effectively treated by an open or laparoscopic cystgastrostomy, draining the cyst into the back wall of the stomach and performing simultaneous surgical debridement of any necrotic tissue within the cavity. Patients presenting with sepsis within the first 4 weeks require a different strategy. Separation of the devitalised tissue is incomplete and the cavity wall immature. A series of surgical approaches have been described in the last 20 years; all of these recognised the fundamental importance of addressing the solid necrotic component within the infected cavity, with differing approaches to the post-operative management of the necrosectomy cavity. Necrosectomy with post-operative cavity tube drainage was associated with an improved outcome compared to resective procedures or simple peritoneal lavage [22], but the requirements for repeated surgical intervention remained, mainly due to recurrent sepsis. This led to the development of techniques such as open packing [23] or the utilisation of prolonged post-operative cavity lavage [24]. Debridement followed by closure over drains was described by Warshaw and Jin [22] in 1985, and their results were updated in 1999. In the later paper, they described a series of 64 patients, of whom 36 had infected necrosis. Only 31% had organ failure. Overall mortality was only 6.2% and the outcome appeared to be unrelated to the presence of infection. Bradley [23] described the technique of ‘open packing’, using lubricated gauze swabs to pack the surgical cavity following necrosectomy in 28 patients with infected ne-
Carter
Fig. 1. Percutaneous necrosectomy: nephroscope access to necrosis using a 34-FG Amplatz sheath.
crosis, and reported a mortality of 11%. More recently, in 1998, a Dutch group [25] reported their results using this technique in 27 patients with necrotising pancreatitis, with major complications in 14, recurrent abscesses in 9 and a mortality rate of 39%. In contrast, Branum et al. [26] reported a 12% mortality rate with a similar approach in 50 patients, of whom 84% had infected necrosis. Perhaps the most commonly adopted approach is that of closed lavage of the debrided cavity, first described by Beger et al. [27] in 1982, where they reported their experience in treating 118 patients with pancreatic necrosis, only some of whom were infected. Overall mortality was 33%. Several subsequent reports from the same group have reported mortality rates from infected necrosis of 32.1% [28], 37.8% [9] and 25.2% [20]. Büchler et al. [29] reported a mortality of 24% using this technique; however, the most impressive figures were reported by Farkas et al. [30], with an overall hospital mortality of 7% in 123 patients with infected necrosis. The differing success reported by groups using apparently similar approaches illustrates the difficulties in comparing different or evolving techniques performed around the world. Most techniques have an average mortality rate of between 20 and 25%; however, the mortality in patients with established multiple organ failure may exceed 75%. Open surgical approaches are associated with a universal initial post-operative deterioration, which many patients who require cardio-respiratory and renal support pre-operatively do not survive. The almost prohibitory
mortality has led to the development of minimally invasive procedures in an attempt to address the specific problems of this small subgroup of high-risk patients. Perhaps the simplest approach to reducing the surgical insult is to reduce the size of the incision. Fagniez et al. [31] described a lateral (retroperitoneal) technique utilising a limited loin/subcostal, retrocolic approach for debridement of pancreatic and peri-pancreatic necrosis. The technique was, however, associated with major morbidity (enteric fistula 45%, haemorrhage 40% and colonic necrosis 15%), and has not gained popularity. The Leeds group has confirmed the feasibility of a formal laparoscopic necrosectomy. The technical laparoscopic expertise required has limited its more widespread adoption, but the results of their series are awaited with interest. Developments in interventional radiology have revolutionized the management of many surgical conditions; however, in the presence of pancreatic necrosis, simple aspiration and percutaneous drainage alone rarely result in resolution in that they do not address the solid component within the abscess, and should therefore be discouraged as sole treatment. They may have a role as a temporising measure in the hope of finding a ‘window of opportunity’ in which to perform definitive intervention. The radiological approach was taken to its limits by Freeny et al. [32], who combined aggressive CT-guided percutaneous drainage with continuous post-drainage lavage and showed that the pancreatic sepsis may resolve; however, nearly three quarters of the patients will subsequently require surgical intervention. The logistic demands on the
Minimally Invasive Pancreatic Necrosectomy
Pancreatology 2003;3:133–138
135
radiological department of this approach have lessened its universal appeal. In 1996, Baron et al. [33] described a variation on this approach, combining endoscopic cystgastrostomy with naso-cyst lavage, and reported good results in an initial series of eleven patients. Three quarters of their patients had pseudocysts rather than abscesses (only 28% were infected at the time of drainage), at a median of 7 weeks following the onset of their illness. It is worthy of note that up to 60% of those patients successfully drained developed further collections in the subsequent 2 years [34]. This series confirmed that in the presence of necrosis, therefore, drainage must be combined with some form of surgical removal of the necrotic material. This technique has been further refined and significant tract dilatation is possible endoscopically, allowing limited debridement of necrosis. In 2000, we described [35] our technique of percutaneous necrosectomy involving intraoperative dilatation of a percutaneous drain tract, and subsequent necrosectomy using a urological rigid rod lens system, usually from the left flank or a right subcostal approach. To avoid contamination by bowel puncture, double-contrast CTguided FNA is performed. Our preferred route is through the left fat plane between the spleen posteriorly and the colon anteriorly, although for right-sided collections, access can usually be obtained anterior to the duodenum, between colon and liver. The tract is first dilated using a balloon dilator, allowing insertion of a 34-FG Amplatz sheath. Initial intermittent copious lavage and suction is performed until the irrigant clears sufficiently to be able to see within the cavity. Devitalised tissue is easily identified and can be removed by gentle traction in a piecemeal fashion. Experience has suggested that overzealous attempts at cavity clearance are unnecessary and can lead to bleeding. An 8-FG umbilical catheter sutured to a 28-FG tube drain is then passed to the far end of the cavity to allow continuous post-operative lavage (500 ml/h, Dianil 7) via the umbilical catheter. Planned second-look procedures are then performed every 7–10 days, until the cavity is clean. Most centres have reported the results of a consistent method of treatment, comparing their results to those of other centres, where referral practice, selection criteria, background morbidity and therefore outcome may differ considerably. We have now treated over 35 patients using this technique. We have reported our initial experience [35]; however, we wish to reserve our conclusions on efficacy until we have treated an appropriately large series of patients, so that we may compare these with our patients
136
Pancreatology 2003;3:133–138
managed by traditional open techniques. Early observations have shown a reduction in the almost universal deterioration in organ function following an open approach, and therefore a significant reduction in the need for postoperative intensive care management. Whether this is extrapolated into a reduction in mortality remains unanswered. The preliminary results have been encouraging; however, ongoing assessment of this approach continues.
Minimal Access Surgical Intervention
The disappointingly high mortality associated with infected necrosis in 2002, despite advances in critical care support and the variety of possible surgical, endoscopic and radiological approaches, is an indication that no single technique provides an answer. Within the surgical literature, it is impossible to determine the hidden effects of factors such as referral pattern, patient selection, pre-surgical percutaneous management and population morbidity. Improvements in outcome over historical controls also have to be considered against a background of simultaneous advances in general intensive care patient management. Indications for necrosectomy also vary widely, and authors have tended to combine management of late abscesses with cases of true infected necrosis. Individual surgical units have tended, probably inappropriately, to consider their own surgical approach to this complex group of patients as a panacea, comparing results to historical controls or with other reported series. Background morbidity of patients within a series is difficult to determine and undoubtedly has a major influence on outcome. Half of those patients dying as a result of severe acute pancreatitis do so within the first few days of the illness, and may never reach a specialised unit, whilst others may not be considered fit for intervention. As the reported mortality relates only to the surgically treated patients rather than the background denominator group, series may underestimate mortality. Small numbers in reports also result in differing rates from individual centres over time. Referral patterns, co-morbidity and selection criteria therefore may be some of the reasons why clinicians have struggled to emulate in practice some of the mortality rates reported in the literature [30]. For most major centres, overall mortality remains between 20 and 25%, and is significantly higher in the high-risk group with established multiple organ failure. The relative infrequency of patients requiring intervention results in most surgeons adopting a favoured, but consistent, approach to infected necrosis. Within special-
Carter
ized units, it has become increasingly obvious that not all patients respond equally to a given surgical stimulus. Those patients with infected necrosis but without significant organ dysfunction will generally do well regardless of the approach chosen. In these patients, an aggressive surgical approach will address the sepsis, eliminate the necrosis and potentially result in a more rapid recovery. In patients at the severe end of the disease spectrum with established organ dysfunction, traditional intervention is associated with significant mortality, and these patients may benefit from a more flexible approach to the control of sepsis. It may be through utilizing a minimal access technique that improvements in outcome may be achieved. Undoubtedly, the severity of systemic sepsis and organ dysfunction can be reduced by percutaneous or endoscopic drainage; however, the improvement tends to be temporary unless drainage is maintained through some means of addressing the solid component of these abscesses. Tract dilatation and minimally invasive necrosectomy achieves drainage and addresses the solid component, whilst minimizing the surgical insult to the patient. No randomised studies exist comparing one management technique with another. All studies have tended to involve small numbers of patients and have reported a retrospective review of results. Patient selection criteria and patient comorbidity vary enormously. Consequently, it is impossible to draw firm conclusions from the literature, apart from the fact that regardless of the approach
adopted, mortality remains high. The traditional approach has been to compare the results of different techniques of open or minimally invasive necrosectomy. This represents an over-simplification of the clinical complexity posed by these patients, and improvements in outcome are more likely to be achieved through utilisation of a variety of techniques rather than the universal adoption of a single surgical method. We first performed a percutaneous necrosectomy out of necessity in a patient who was otherwise being considered for withdrawal of treatment. Latterly, we continued our series in order to confirm the feasibility of the technique and to address some of the practical issues raised. From our pilot data, our overall results appear at least as good as our historical controls; however, in future we may well limit the use of this approach to specific indications, or as part of a multimodality strategy in critically ill patients. The specific role of percutaneous necrosectomy remains to be clarified; however, the debate should not be about which technique is best, but rather which of the many surgical options most closely addresses the complex needs of the individual patient.
Acknowledgements I would like to acknowledge the contribution of my colleagues Mr. Colin McKay, Professor Clem Imrie and the members of the West of Scotland Pancreatic Research Unit to this work.
References 1 Bradley EL III: A clinically based classification system for acute pancreatitis. Summary of the International Symposium on Acute Pancreatitis, Atlanta, Ga, September 11 through 13, 1992. Arch Surg 1993;128:586–590. 2 Buter A, Imrie CW, Carter CR, Evans S, McKay CJ: Dynamic nature of early organ dysfunction determines outcome in acute pancreatitis. Br J Surg 2002;89:298–302. 3 McKay CJ, Imrie CW: Staging of acute pancreatitis: Is it important? Surg Clin North Am 1999;79:733–743. 4 Larvin M, McMahon MJ: APACHE-II score for assessment and monitoring of acute pancreatitis. Lancet 1989;ii:201–205. 5 McKay CJ, Evans S, Sinclair M, Carter CR, Imrie CW: High early mortality rate from acute pancreatitis in Scotland, 1984–1995. Br J Surg 1999;86:1302–1305. 6 Mutinga M, Rosenbluth A, Tenner SM, Odze RR, Sica GT, Banks PA: Does mortality occur early or late in acute pancreatitis? Int J Pancreatol 2000;28:91–95.
Minimally Invasive Pancreatic Necrosectomy
7 Meir J, Luque-de Leon E, Castillo A, Robledo F, Blanco R: Early versus late necrosectomy in severe necrotising pancreatitis. Am J Surg 1997;173:71–75. 8 Gloor B, Müller CA, Worni M, Martignoni ME, Uhl W, Büchler MW: Late mortality in patients with severe acute pancreatitis. Br J Surg 2001;88:975–979. 9 Beger HG, Bittner R, Block S, Büchler M: Bacterial contamination of pancreatic necrosis. A prospective clinical study. Gastroenterology 1986;91:433–438. 10 Johnson CD, Kingsnorth AN, Imrie CW, McMahon MJ, Neoptolemos JP, McKay C, Toh SK, Skaife P, Leeder PC, Wilson P, Larvin M, Curtis LD: Double blind, randomised, placebo controlled study of a platelet activating factor antagonist, lexipafant, in the treatment and prevention of organ failure in predicted severe acute pancreatitis. Gut 2001;48:62–69. 11 Bradley EL III, Allen K: A prospective longitudinal study of observation versus surgical intervention in the management of necrotizing pancreatitis. Am J Surg 1991;161:19–25.
12 Beger HG, Rau B, Mayer J, Isenmann R: Surgical treatment of acute pancreatitis; in Lankisch PG, DiMagno EP (eds): Pancreatic Disease: State of the Art and Future Aspects of Research. New York, Springer, 1999, pp 78–89. 13 Gloor B, Uhl W, Müller CA, Büchler MW: The role of surgery in the management of acute pancreatitis. Can J Gastroenterol 2000; 14(suppl D):136D–140D. 14 Buchler P, Reber HA: Surgical approach in patients with acute pancreatitis. Is infected or sterile necrosis an indication – in whom should this be done, when, and why? Gastroenterol Clin North Am 1999;28:661–671. 15 Moynihan B: Acute pancreatitis. Ann Surg 1925;81:132–142. 16 Hollender LF, Meyer C, Keller D: Planned operations for necrotising pancreatitis: The continental experience; in Howard JM, Jordan GL Jr, Reber HA (eds): Surgical Diseases of the Pancreas. Philadelphia, Lea and Febiger, 1986, pp 450–460.
Pancreatology 2003;3:133–138
137
17 Mayer AD, McMahon MJ, Corfield AP: Controlled clinical trial of peritoneal lavage for the treatment of severe acute pancreatitis. N Engl J Med 1985;312:399–404. 18 De Beaux AC, Palmer KR, Carter DC: Factors influencing morbidity and mortality in acute pancreatitis; an analysis of 279 cases. Gut 1995;37:121–126. 19 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;85:179–184. 20 Isenmann R, Beger HG: Natural history of acute pancreatitis and the role of infection. Baillière’s Best Pract Res Clin Gastroenterol 1999;13:291–301. 21 Buter A, Eskdale J, Gallagher G, Robertson S, Evans S, Carter CR, Imrie CW, McKay CJ: The IL-10.R3 microsatellite allele is associated with fulminant early organ dysfunction in acute pancreatitis (abstract). Pancreas 1999;19: 417. 22 Warshaw AL, Jin G: Improved survival in 45 patients with pancreatic abscess. Ann Surg 1985;202:408–415. 23 Bradley EL III: Open packing in infected pancreatic necrosis. Dig Surg 1997;14:77–81.
138
24 Rau B, Beger HG: Necrosectomy and closed irrigation for necrotizing pancreatitis. Probl Gen Surg 1996;13:137–145. 25 Bosscha K, Hulstaert PF, Hennipman A, Visser MR, Gooszen HG, van Vroonhoven TJ, v d Werken C: Fulminant acute pancreatitis and infected necrosis: Results of open management of the abdomen and ‘planned’ reoperations. J Am Coll Surg 1998;187:255–262. 26 Branum G, Galloway J, Hirchowitz W, Fendley M, Hunter J: Pancreatic necrosis: Results of necrosectomy, packing, and ultimate closure over drains. Ann Surg 1998;277:870–877. 27 Beger HG, Krautzberger W, Bittner R, Block S: Necrotizing pancreatitis. Indication for operation and results in 118 patients (in German). Chirurg 1982;53:784–789. 28 Beger HG, Krautzberger W, Bittner R: Results of surgical treatment of necrotizing pancreatitis. World J Surg 1985;9:972–979. 29 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;232:619–626.
Pancreatology 2003;3:133–138
30 Farkas G, Marton J, Mandi Y, Szederkenyi E: Surgical strategy and management of infected pancreatic necrosis. Br J Surg 1996;83:930– 933. 31 Fagniez PL, Rotman N, Kracht M: Direct retroperitoneal approach to necrosis in severe acute pancreatitis. Br J Surg 1989;76:264–267. 32 Freeny PC, Hauptmann E, Althaus SJ, Traverso LW, Sinanan M: Percutaneous CT-guided catheter drainage of infected acute necrotizing pancreatitis: Technique and results. AJR Am J Roentgenol 1998;170:969–975. 33 Baron TH, Thaggard WG, Morgan DE, Stanley RJ: Endoscopic therapy for organized pancreatic necrosis. Gastroenterology 1996;111: 755–764. 34 Adkisson KW, Morgan DE, Baron TH: Long term outcome following successful endoscopic drainage of organised pancreatic necrosis (OPN): Skunkpoking revisited (abstract). Gastrointest Endosc 1997;45:514. 35 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; 232:175–180.
Carter