Management of Infected Pancreatic Necrosis Mike Larvin, MD, FRCS
Corresponding author Mike Larvin, MD, FRCS Division of Surgery, School of Graduate Entry Medicine and Health, University of Nottingham at Derby, Derby City General Hospital, Derby, DE22 3DT, UK. E-mail:
[email protected] Current Gastroenterology Reports 2008, 10:107–114 Current Medicine Group LLC ISSN 1522-8037 Copyright © 2008 by Current Medicine Group LLC
The past two decades have seen major advances in the understanding and clinical management of acute pancreatitis, yet it still lacks a specific treatment, and management is largely supportive and reactive. Surgery is seeing a diminishing role in the early phase of acute pancreatitis but still predominates in the management of infected pancreatic necrosis—the most lethal complication. This review focuses on recent literature but begins with an account of the evolution of infected necrosis management, which serves to place current treatment into context. Although surgeons initially emphasized less invasive approaches to pancreatic necrosis, they now compete with new techniques developed by pioneering physicians, radiologists, and interventional endoscopists. Clinicians adopting the new techniques will need to emulate the dedication and commitment that the current pioneers demonstrate. Although new techniques are still evolving, they should be evaluated against existing standards of treatment.
Introduction Acute pancreatitis remains one of the most lethal and unpredictable of all acute gastrointestinal disorders. Most attacks follow a mild course with prompt recovery, but about 25% are severe. Death may result from fulminant multiple organ system failure within a few days. Areas of ischemia may progress to necrosis, and this fuels an initially sterile inflammatory reaction. Almost all fatalities are associated with pancreatic necrosis. Survivors from early organ system failure may still die if pancreatic necrosis later becomes infected. Just three decades ago, this would have mandated aggressive surgical intervention, with an often fatal outcome.
Definitions Life-threatening complications were first properly defined at the 1992 Atlanta International Symposium on acute pancreatitis [1]. Attacks are classified as severe when complicated by organ system failure or a pancreatic collection: necrosis, abscess, or pseudocyst. Pancreatic necrosis was defined as focal or diffuse well-defined zones of nonenhancing pancreas not less than 3 cm in diameter or 30% of pancreatic volume on contrast-enhanced CT. Refined criteria are due to be published in 2008.
Natural History No specific therapy can ameliorate early multiple organ system failure. In a large series of 1150 attacks [2], 28 deaths (51%) occurred within 2 weeks and 27 (49%) afterward. Early deaths resulted primarily from organ system failure, and later deaths from infected necrosis. A review that analyzed previous series reporting the timing of death reminds us that deaths do still happen in the first week, although more than half occur later [3]. Reported series suggest an incidence of pancreatic necrosis of about 20% of attacks, with infection complicating 40% to 70%. Time and again, underlying necrosis has shown up as the single most frequent association with death. Treatments aimed at preventing necrosis could improve outcome. One recent report showed significant early macrovascular changes in patients with CT-proven necrosis, evidenced on angiography by intrapancreatic and extrapancreatic vasospasm corresponding with areas of necrosis [4]. The microvascular circulation also appears crucial. The pancreatic acinus is surrounded by a large network of very fine capillaries. Such an arrangement means that diminution of inflow or local vasospasm predisposes to edema, transmigration of inflammatory cells, and necrosis.
Diagnosing Pancreatic Necrosis Pancreatic necrosis cannot be detected at laparotomy, by ultrasonography, or by conventional CT imaging and is best diagnosed from reduced perfusion on high-dose intravenous contrast-enhanced CT. A recent study confirmed previous reports that unenhanced MRI is a useful
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alternative to CT [5•]. It evaluated contrast-enhanced spiral CT and unenhanced MRI within 5 days of admission in 101 attacks. Nonenhanced MRI was comparable to contrast-enhanced CT for detecting necrosis, but MRI had the edge on detecting gallstones.
Infection Infected necrosis is diagnosed from bacteriological culture of samples obtained from operation or other intervention, autopsy, or image-guided fine-needle aspiration. Banks [6] and Pappas [7] did a great job in marshalling the important arguments “for and against” aspiration in interesting side-by-side contributions. The incidence of infected pancreatic necrosis varies. It was recently reported from Ulm, Germany, to be 8% to 12%; however, this could reflect specialist transfers [8]. In 1986, the same unit provided the first evidence that infection presents most often in the second to third week after onset. In a series from Switzerland, infection was also detected after an average 21 days from onset [9], whereas more recently, another German center confirmed infection after an average 19 days from admission [10].
Outcome of infected pancreatic necrosis The development of infection is pivotal in determining the outcome of pancreatic necrosis. Necrosis was quantified in a series of 104 cases [11]. Some 74 cases remained sterile, whereas 30 became infected. Logistic regression confirmed a significant association with the extent of necrosis and infection. Overall mortality was 22%, and significant predictors were the presence of infected necrosis and Acute Physiology and Chronic Health Evaluation (APACHE II) scores. In a similar study of 165 attacks [12], one third involved necrosis, and more than one quarter became infected. Organ system failure was significantly more common with necrosis, and more so when this exceeded 50% or became infected. Six of eight deaths were associated with infected necrosis.
Prevention of infection The mechanism of infection of pancreatic necrosis is unclear, but as the infecting agent is usually enteric, translocation from nearby gut has been implicated. A recent review critically examined the animal models used to investigate translocation [13•]. The exact mechanism, origin, and route of bacteria and, thus, treatment strategies remained unclear. Many experimental techniques interfere with intestinal flora, mucosal barrier function, or immune responses. The necrotic sequestrum is at risk from surrounding perfused tissues, lymphatic fluid, and its “buddy next door,” the gut. Intestinal permeability is significantly increased in severe attacks, which would encourage bacterial translocation [14]. Prophylactic antibacterial therapy appears logical, but its role remains unclear after more than a decade of randomized controlled trials of variable
quality, none of which possessed an adequate sample size. Many reviews have been devoted to this vexatious topic, but a recent meta-analysis suggested that antibiotics reduce mortality only by nonspecific effects on extrapancreatic sepsis, such as respiratory infection, rather than preventing necrosis infection [15]. Further trials are required.
Principles of Treatment of Infected Pancreatic Necrosis The principles underlying the treatment of infected pancreatic necrosis are simple: as much infected material should be removed as safely as possible, followed by adequate drainage to prevent recurrence. The term debridement is used consistently in this review, but it is interchangeable with necrosectomy or sequestrectomy. There are no indications for surgical intervention during the first week of attacks, except for acute abdominal hypertension from retroperitoneal and mesenteric engorgement, which can worsen acute respiratory and renal failure. This can be diagnosed from transducing a urinary catheter. An “open laparostomy” vents excess pressure, but this may now be accomplished by subcutaneous abdominal fasciotomy [16•]. An interesting study recently validated two CT features of intra-abdominal hypertension [17•]: the “round belly sign” and “bowel wall thickening with enhancement”; both significantly predicted abdominal hypertension, and the latter significantly predicted progression to compartment syndrome.
Techniques of debridement Necrotic pancreas is not easily digitally debrided until several weeks have elapsed, when it separates and becomes encapsulated. This is now termed “organized” or “walled-off” necrosis (Fig. 1). This decreases the risk of hemorrhage and spares vital pancreatic tissue and, thus, long-term pancreatic function. Open packing of the abdomen may be used if an earlier operation is necessary. The necrotic sequestrum liquefies and is removed by daily pack changes until resolution. Debridement is otherwise usually combined with prolonged postoperative drainage by lavage or closed packing. Only one randomized controlled trial has addressed debridement, but it was published more than 10 years ago. Mier et al. [18] conducted a comparison of early (48–72 hours) versus delayed (> 12 days) open packing. There was increased mortality in the early group, at 58% versus 27%, so the trial ceased early.
Evolution of conservative management For some years, pancreatic necrosis was pretty much a passport to surgical debridement. The development of improved imaging, an ability to detect infection by fine-needle aspiration, and experience with occasional patients felt unfit for debridement challenged this. In 1991, Bradley and Allen [19] established the first landmark, when 11 patients with confirmed sterile necrosis
Management of Infected Pancreatic Necrosis Larvin 109 Figure 1. Anatomic approaches to infected pancreatic necrosis include transluminal: transgastric (1), transgastrostomy (2), and transduodenal (3); flank/retroperitoneal: right retroperitoneal (4) and left retroperitoneal (5); and transperitoneal: retroduodenal (Kocherization) (6), transgastric (7), gastrocolic (8), and inframesocolic (9).
Spleen Stomach 2
1
5
Left kidney
4 3
Right kidney 6
7
8,9
were treated successfully without surgery. The next landmark was reached in 1996, when Dubner et al. [20] reported on three patients with proven infected necrosis and peripancreatic collections who were too unstable or expressed a preference for medical therapy; all survived. Intervention is reserved now for progressive deterioration despite maximal intensive therapy, including targeted antibacterial therapy. More recent series continue to support this policy. In a report of 88 consecutive cases managed medically, 28 developed infected necrosis on fine-needle aspiration [10]. Only 12 required surgery, and the remaining 16 were managed medically. Of these, six recovered without further complication. Ten patients developed single or multiple organ system failure, two of whom died (12%). Case records of 52 patients with severe acute pancreatitis were analyzed in another recent report [21]. Of 24 cases of infected necrosis, 18 deteriorated and were debrided surgically, with five deaths (28%). The remaining six received prolonged medical management and recovered. There may be some downsides to prolonged medical management. In 2004, a case report described the death of a 62-year-old with diffuse intrapancreatic gas who underwent immediate laparotomy, finding diffuse pancreatic necrosis [22]. The patient died soon afterward
and Clostridium perfringens was cultured. “Gas gangrene” was also the subject of a report of a 67-year-old whose CT revealed copious peripancreatic gas [23]. Surgical intervention confirmed C. perfringens. The patient suffered hemolysis yet was discharged 8 weeks later. Another report described two patients with pancreatic necrosis with a “soap bubble” sign of retroperitoneal gas on CT early in their attacks [24•]. Both were desperately unwell but creditably survived extensive surgery. Bacteriology confirmed C. perfringens. Extensive gas in a deteriorating patient is not an indication to sit tight with conservative management. Microbial resistance Microbial resistance is a known problem with prolonged use of antibiotics and is a known issue for conservative management. In a recent report of 56 consecutive attacks managed in one intensive care unit [25], antibiotic-resistant organisms were found in 24 cases, resulting in significantly longer intensive care unit stays but not increased mortality. A retrospective review examined 73 debridement patients, of whom 55 had documented infection at the first procedure [26]. Of these, 21 had bacteria resistant to previous prophylactic antibiotics, but again this was not associated with increased mortality. Of six
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patients with fungal infection, five died, and all six presented with significantly higher APACHE II scores. In 66 secondary infections, 21 developed fungal infection, of whom 10 died, compared with only 11 of 45 others. In another series of 13 patients with infected necrosis, a change was noted over time to a preponderance of gramnegative and fungal infection [27].
Open debridement Open debridement continues to be the “gold standard” intervention for infected pancreatic necrosis. However, it is usually now only performed after failed conservative management. That rationale for conservative management was confirmed as early as 2000 by Büchler et al. [9], on the basis of a large series over 5 years of operating only on confirmed pancreatic infection. All other patients were treated nonsurgically. Of 204 consecutive attacks, 86 involved pancreatic necrosis, which was sterile in 57 cases (66%) and infected in 29 cases (34%). On an intention-to-treat analysis, mortality was 5% for sterile necrosis managed conservatively versus 21% for infected necrosis. Necrosectomy and continuous closed lavage were successful in 67% of cases, but 22% needed a second intervention and 11% an additional interventional procedure. Of 56 patients with sterile necrosis managed medically, only one died due to severe respiratory distress syndrome. Several decades of experience in Ulm, Germany, also confirmed that surgical intervention is best reserved for patients with proven infected pancreatic necrosis who are beginning to deteriorate [8]. Of 60 consecutive patients reported to have severe pancreatitis, 42 had pancreatic necrosis on CT, of which 13 were infected and 29 sterile [27]. All those with infected necrosis and eight with sterile necrosis underwent open operative debridement; all 39 others were managed successfully nonoperatively. Overall mortality was 15%. A planned staged necrosectomy using the “zipper” technique was used in 35 patients with infected pancreatic necrosis [28]. Overall mortality was 34%. There were 16 fistulae in 11 patients (31%), recurrent intra-abdominal abscesses in four (11%), and hemorrhage in five (14%). Multivariate logistic analysis demonstrated that admission APACHE II scores exceeding 13 or paracolic necrotic extension were significant predictors of death. Pancreatic necrosis was confirmed in 14 of a reported series of 373 patients (3.8%) [29]. All had infected necrosis; eight underwent debridement and drainage, and six patients open packing. All deaths occurred in open packing. Mortality for debridement prior to 4 weeks after onset was 33%, 25% after 4 weeks, and 0% after 6 weeks. The overall mortality rate was 29%. A retrospective study reported 106 consecutive patients debrided by various means [30•]. Laparotomy with postoperative lavage was the strategy most often used. Overall mortality was 34%: 70% for an open packing, 25% for postoperative lavage, 11% for minimally invasive procedures, and 42% for primary abdominal closure.
Evolution of alternatives to surgical debridement The rationale for minimally invasive approaches is to minimize perioperative and postoperative stress in seriously unwell patients with multiple organ system failure. It may also extend indications for intervention to patients otherwise unfit for surgery. Additionally, these techniques may be used to initially control sepsis and thus usefully delay more major surgery until there is better demarcation of necrotic tissue. The first such approach is the use of percutaneous catheter drainage. A group from Louisiana changed from a surgical approach during the 1980s to an initial nonoperative approach using CT-guided catheter drainage from 1989 [31]. In the first period, 6 of 7 necrosis patients died after multiple operations. After the policy change, 19 patients developed necrosis, with only two deaths after nonoperative treatment. However, two patients (15.8%) subsequently underwent laparotomy for collections not drainable using CT guidance. Overall mortality was reduced to 10.5% from 86%, but morbidity approached 70%. Many other changes in management would have occurred during this period. Freeny et al. [32] reported complete resolution of sepsis in 47% of patients with established infected necrosis after aggressive percutaneous drainage. This included aggressive lavage through multiple large-diameter catheters. Thirty-four patients unwell with infected necrosis underwent repeated exchanges to remove necrotic material, with an overall mortality of 12%. Surgery was avoided in almost half, but many who required it were able to delay it until they were more stable. A mean of four catheter insertions and lavage for an average of 85 days were required. A study reported a series of 82 patients with CT-guided aspiration for suspected pancreatic sepsis [33]. In all, 135 aspirations were performed, and all patients received antibiotics. Cultures were positive in 42, and 25 (60%) of these patients underwent percutaneous drainage, of whom six later required surgery. Mortality was 12% for culture-positive patients and 8% for the entire series. The authors recognized that percutaneous drainage was not a panacea but argued for its consideration as initial therapy for culture-positive patients, reserving surgical intervention for those in whom treatment fails. Great dedication was required by the radiologists concerned, and this may not be reproducible elsewhere. Laparoscopic approaches The trauma of open abdominal access has also been shown to trigger a more deleterious intraperitoneal and systemic cytokine-mediated immune response compared with a laparoscopic equivalent, although not specifically for pancreatic necrosis. These approaches are still characterized by relatively few reports of small numbers of cases, and there is little evidence of greater uptake by pancreatic surgeons. A case report described the treatment of a patient with necrosis of the pancreatic body and tail [34]. CT and
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fine-needle aspiration proved gram-negative infection. Surgery was deferred to week 6 while necrosis matured. A laparoscopic transgastric approach was used, and the patient made an uneventful recovery with discharge on the 14th postoperative day. A series of three patients had a preexisting percutaneous drainage tract dilated so that a working thoracoscope could be inserted [35]. Pulsatile irrigation was used to open the cavity and wash away necrotic debris. A large drainage tube was placed for the egress of residual material. All three patients were treated successfully, with no intraoperative complications. A novel technique was used in 19 patients undergoing pancreatic debridement [36•]. A hand-assist gel port provided laparoscopic hand access. The procedure was completed in 18, and four required reoperations (two hand assist, two open). There were no postoperative complications related to the procedure and two deaths (11%). However, one surgeon’s experience extends from the first reports in 1996 and led to evolution of various routes of access to the necrotic cavity [37]. Transabdominal, retrogastric, retrocolic, and retroperitoneal routes were described for the early infected phase, whereas a transgastric approach was suggested for late-onset infected necrosis. The success rate after a single procedure was 75% in eight patients, with no mortality. Retroperitoneal approach In 2000, Carter et al. [38] reported 14 consecutive cases in which four patients underwent endoscopy along a retroperitoneal flank drainage tract after open necrosectomy; no patients died. Primary debridement for proven infected necrosis was carried out wholly percutaneously in 10 more patients. A radiologically inserted 8F pigtail nephrostomy catheter afforded access, and after dilatation an operating nephroscope was passed, removing solid material with forceps. A large tube drain was passed for postoperative lavage and continued until fluid cleared. A twin-channel flexible endoscope was also used with jet irrigation to mobilize adherent necrosis and slough. Eight patients recovered after a median of three percutaneous retroperitoneal explorations. There was one conversion for intraoperative bleeding. Right-sided access was difficult and dependent postoperative drainage harder to achieve. Only 40% of patients required intensive care management after surgery, and two patients died. In the largest series reported to date, 41 open and 47 minimally invasive debridements were compared [39]. Univariate analysis showed the latter was associated with significantly lower postoperative APACHE II scores and shorter postoperative intensive care, but no significant difference in mortality. Twelve patients treated in a minimally invasive manner required an additional open procedure for secondary hemorrhage, colonic ischemia, inaccessible collections, or persisting sepsis. Overall morbidity was 92% and mortality 28%. Some 62% of survivors experienced complications, and 16% required
further intervention. Just under one half were unsuitable for a minimally invasive approach, and technical difficulties or complications reduced this to about one third. Sinus tract endoscopy was used to treat 13 patients with extensive necrosis, nine of whom had first been managed by percutaneous drainage and four by open debridement [40]. Therapy was more successful after open debridement than after prior percutaneous drainage. Transgastric endoscopic approach Pseudocysts and pancreatic abscesses have long been amenable to transgastric drainage by stented cystogastrostomy under endoscopic retrograde cholangiopancreatography or endoscopic ultrasound (EUS) control. It is a logical extension to attempt to treat infected pancreatic necrosis in this way. Baron et al. [41] pioneered this, first reporting outcome data in 11 patients with organized pancreatic necrosis in 1996. Most did not have infected necrosis. An 8-mm stoma was created after initial precut into the gastric or duodenal wall, and catheters were inserted with nasal irrigation tubes for lavage. Procedures were repeated three times on average. There were serious complications in almost half, including hemorrhage and gastric perforation, but debridement was achieved in all but two patients without a death. Regular reports followed as the technique evolved. Seifert et al. [42] also reported entry into the cavity by precut needle and the use of a gastroscope for debridement with a urologic basket. In one of three patients treated, a necrotic spleen was removed transgastrically. This was quite a feat. An aggressive endoscopic approach was reported with synchronous EUS-guided multiple transmural or transpapillary drainage, balloon dilation of the stoma, daily necrosectomy and saline lavage, and sealing of pancreatic fistula with cyanoacrylate [43••]. Pancreatic necrosis and pancreatic abscesses were successfully drained in 13 patients, avoiding emergency surgery, and surgery was completely avoided in nine patients with no major complications. Surgery was required in four cases for retroperitoneal extension and later pseudocyst formation. In 2005, an editorial cautioned about endoscopic therapy for pancreatic necrosis, which was considered not suitable for the time challenged or endoscopists without EUS or surgical and interventional radiologic support [44]. The intensity of treatment and personal commitment displayed by the few current pioneers in the United States and Europe was noted. Thirteen patients underwent a median of four endoscopic transgastric debridements [45]. Clearance of necrosis was achieved by repeated irrigation and introduction of stone retrieval baskets into the cavity and was successful in 12 cases. One patient required open surgery, two underwent auxiliary percutaneous debridements, and another underwent laparoscopic drainage. Two patients died of unrelated complications. Double endoscopic gastrostomy access was successfully
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used after endoscopic necrosectomy for necrosis in two patients [46]. This allowed enteral nutrition to be continued as well as flushing of the cavity. A retrospective analysis of endoscopic treatment was carried out in 25 patients with 27 “necrotic collections” [47•]. Indications were organized necrosis despite conservative treatment in eight, suspicion of infection in five, and secondary infected necrosis after earlier endoscopic or surgical drainage in 14. Although there was no mortality, hemorrhage and perforation required surgery in two cases. It is difficult to draw conclusions from such an unusual case mix. The recent report from Papachristou et al. [48••] described a total of 53 cases treated by transoral, transmural endoscopic drainage and debridement from 1998 to 2006. More than one half proved to have sterile necrosis and perhaps did not require intervention. All had “walled-off pancreatic necrosis” indicating maturity. A median of three interventions began after a median 49 days. In almost one half, concurrent radiologic-guided catheter drainage was performed. Almost one quarter required open operation. The final outcome was judged successful in 43 (81%), but necrosis persisted in 10 (19%). Preexistent diabetes, extent of necrosis, and paracolic gutter involvement predicted an open procedure. The authors suggested that an alternative might be to combine percutaneous, laparoscopic, and nephroscopic approaches, or even a small incision for focused debridement. Nonsurgical management for infected pancreatic necrosis was evaluated in 31 Korean patients [49]. Nonsurgical percutaneous or endoscopic drainage was initially tried, reserving surgery for patients with no clinical improvement. Percutaneous or endoscopic drainage was carried out in 18 and five patients, respectively, and eight received antibiotics only. Four patients, three from the percutaneous and one from the endoscopic drainage group, required surgery. One patient died from fulminant multiple organ system failure. Seven patients had to be readmitted with fever, and the drainage tube was repositioned.
Preventing Recurrence Having survived treatment for infected pancreatic necrosis, few patients would wish to suffer a further attack. It is important to seek the cause of the attack and eliminate it. Most commonly, this will take the form of treatment for gallstones or cessation of alcohol, but other etiologies may have to be considered. A recent report by Howard and Temple [50] highlighted a preventable cause of recurrence. The authors reported by retrospectively reviewing 98 patients debrided for pancreatic necrosis, of whom 14 (14%) developed recurrent pancreatitis a median 15 months after onset. Nine had radiologic evidence of obstructive pancreatitis,
and all had a high-grade pancreatic duct stricture (7) or complete duct cutoff (7) localized to the pancreatic neck (10) or proximal pancreatic body (4). One explanation for these observations is that the vascular supply to this area may be a “vascular watershed.” All required reoperative treatment, with no recurrence of pancreatitis. The American College of Gastroenterology recently added to the worldwide plethora of guidelines for acute pancreatitis [51•]. This document includes the management of infected pancreatic necrosis. It is extensively referenced and evidence-based and should be required study for everyone dealing with acute pancreatitis.
Conclusions The management of infected pancreatic necrosis is changing rapidly, and we currently rely on experiential reports in the absence of controlled trial data. It appears that traditional principles of surgical therapy for infected pancreatic necrosis could be delivered by several new approaches described recently. Although newer, less invasive interventions offer hope of improved survival and speedier recovery, they have not yet been scrutinized by randomized controlled trials or large-scale experiential evaluation. This is reminiscent of the early days of laparoscopic cholecystectomy, and it will be important not to repeat the mistakes made at the dawn of that era. Enthusiastic early adopters appear to have developed the discipline required to perfect these new interventions. From the current literature, transgastric debridement appears to be leading the pack. Drainage of the infected cavity can be achieved through all of the routes described. Different areas of the pancreas may be more amenable to one technique than others. The tail of the pancreas is less accessible to transgastric drainage, the body less to percutaneous approaches, and the head to retroperitoneal or laparoscopic approaches. Some patients may require a combination of approaches to secure control. Lavage and external drainage may not be as necessary with transgastric drainage, as contents can egress into the gastrointestinal tract. Pancreatologists across various crafts and disciplines already recognize the value of teamwork. A fusion of talent may be the way to improve outcomes. Working together to share surgical, radiologic, and endoscopic skills represents a major paradigm shift, and the prospect of intensive specialist training to marry these skills offers an exciting but daunting prospect. Controlled evaluations will have to wait until techniques have matured.
Disclosure No potential conflict of interest relevant to this article was reported.
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References and Recommended Reading Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance 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. Carnovale A, Rabitti PG, Manes G, et al.: Mortality in acute pancreatitis: is it an early or a late event? JOP 2005, 6:438–444. 3. McKay CJ, Imrie CW: The continuing challenge of early mortality in acute pancreatitis. Br J Surg 2004, 91:1243–1244. 4. Takeda K, Mikami Y, Fukuyama S, et al.: Pancreatic ischemia associated with vasospasm in the early phase of human acute necrotizing pancreatitis. Pancreas 2005, 30:40–49. 5.• Stimac D, Miletic D, Radic M, et al.: The role of nonenhanced magnetic resonance imaging in the early assessment of acute pancreatitis. 2007, 102:997–1004. Despite concerns that consensus reporting may be biased toward a correlation between CT and MRI, this interesting paper confirms previous reports of the value of MRI. MRI was better for visualizing gallstones and also demonstrated pancreatic hemorrhage in a small number of patients, all of whom had a more protracted clinical course. MRI cannot be used in unstable patients, but the absence of ionizing radiation makes it a safer equivalent to CT for children and young adults. 6. Banks PA: Pro: Computerized tomographic fine needle aspiration (CT-FNA) is valuable in the management of infected pancreatic necrosis. Am J Gastroenterol 2005, 100:2371–2372. 7. Pappas TN: Con: Computerized tomographic aspiration of infected pancreatic necrosis: the opinion against its routine use. Am J Gastroenterol 2005, 100:2373–2374. 8. Beger HG, Rau B, Isenmann R: Natural history of necrotizing pancreatitis. Pancreatology 2003, 3:93–101. 9. Büchler MW, Gloor B, Müller CA, et al.: Acute necrotizing pancreatitis: treatment strategy according to the status of infection. Ann Surg 2000, 232:619–626. 10. Rünzi M, Niebel W, Goebell H, et al.: Severe acute pancreatitis: nonsurgical treatment of infected necroses. Pancreas 2005, 30:195–199. 11. Garg PK, Madan K, Pande GK, et al.: Association of extent and infection of pancreatic necrosis with organ failure and death in acute necrotizing pancreatitis. Clin Gastroenterol Hepatol 2005, 3:159–166. 12. Remes-Troche JM, Uscanga LF, Peláez-Luna M, et al.: When should we be concerned about pancreatic necrosis? Analysis from a single institution in Mexico City. World J Surg 2006, 30:2227–2233; discussion 2234–2235. 13.• van Minnen LP, Blom M, Timmerman HM, et al.: The use of animal models to study bacterial translocation during acute pancreatitis. J Gastrointest Surg 2007, 11:682–689. This extensive review details the current status of animal models for studies of translocation in acute pancreatitis. There appears to be no model free of influence on the measurement of translocation; better examples must be developed if more is to be achieved with translocation. 14. Rahman SH, Ammori BJ, Holmfield J, et al.: Intestinal hypoperfusion contributes to gut barrier failure in severe acute pancreatitis. J Gastrointest Surg 2003, 7:26–35; discussion 35–36. 15. Villatoro E, Bassi C, Larvin M: Antibiotic therapy for prophylaxis against infection of pancreatic necrosis in acute pancreatitis. Cochrane Database Syst Rev 2006, (4):CD002941.
16.•
Leppäniemi AK, Hienonen PA, Siren JE, et al.: Treatment of abdominal compartment syndrome with subcutaneous anterior abdominal fasciotomy in severe acute pancreatitis. World J Surg 2006, 30:1922–1924. A truly innovative and less invasive approach to the abdominal compartment syndrome. This is not a common complication but one that often goes undetected because it is not considered. The procedure could be carried out within the intensive care unit in an unstable patient. Note that this paper should be read in combination with the reference by Al-Bahrani et al. [17•]. 17.• Al-Bahrani AZ, Abid GH, Sahgal E, et al.: A prospective evaluation of CT features predictive of intra-abdominal hypertension and abdominal compartment syndrome in critically ill surgical patients. Clin Radiol 2007, 62:676–682. This study is a fascinating way of relating form to function. The round belly sign referred to is not the exclusive preserve of radiologists, and is often pointed out to clinicians by intensive care staff. Although it is easy to measure intravesical pressure as a proxy for intra-abdominal pressure, the message of this paper is that not all units monitor this and it may be picked up serendipitously by CT. 18. Mier J, Leon E, Castillo A, et al.: Early versus late necrosectomy in severe necrotizing pancreatitis. Am J Surg 1997, 173:71–75. 19. Bradley EL 3rd, Allen K: A prospective longitudinal study of observation versus surgical intervention in the management of necrotizing pancreatitis. Am J Surg 1991, 161:19–24. 20. Dubner H, Steinberg W, Hill M, et al.: Infected pancreatic necrosis and peripancreatic fluid collections: serendipitous response to antibiotics and medical therapy in three patients. Pancreas 1996, 12:298–302. 21. Sivasankar A, Kannan DG, Ravichandran P, et al.: Outcome of severe acute pancreatitis: is there a role for conservative management of infected pancreatic necrosis? Hepatobiliary Pancreat Dis Int 2006, 5:599–604. 22. Stockinger ZT, Corsetti RL: Pneumoperitoneum from gas gangrene of the pancreas: three unusual findings in a single case. J Gastrointest Surg 2004, 8:489–492. 23. Ikegami T, Kido A, Shimokawa H, Ishida T: Primary gas gangrene of the pancreas: report of a case. Surg Today 2004, 34:80–81. 24.• De Silva NM, Windsor JA: Clostridium perfringens infection of pancreatic necrosis: absolute indication for early surgical intervention. ANZ J Surg 2006, 76:757–759. A surgical tour de force: without the prompt action of surgical staff, both patients in this study may have succumbed to gas gangrene. The “soap bubble” sign on CT is illustrated, and both cases are well documented. 25. De Waele JJ, Vogelaers D, Hoste E, et al.: Emergence of antibiotic resistance in infected pancreatic necrosis. Arch Surg 2004, 139:1371–1375. 26. Connor S, Alexakis N, Neal T, et al.: Fungal infection but not type of bacterial infection is associated with a high mortality in primary and secondary infected pancreatic necrosis. Dig Surg 2004, 21:297–304. 27. Malangoni MA, Martin AS: Outcome of severe acute pancreatitis Am J Surg 2005, 189:273–277. 28. Radenkovic DV, Bajec DD, Tsiotos GG, et al.: Planned staged reoperative necrosectomy using an abdominal zipper in the treatment of necrotizing pancreatitis. Surg Today 2005, 35:833–840. 29. Lee VT, Chung AY, Chow PK, et al.: Infected pancreatic necrosis: an evaluation of the timing and technique of necrosectomy in a Southeast Asian population. Ann Acad Med Singapore 2006, 35:523–530.
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Besselink MG, de Bruijn MT, Rutten JP, et al.: Surgical intervention in patients with necrotizing pancreatitis. Br J Surg 2006, 93:593–599. A useful preface to the current Dutch PANTER (Pancreatitis, Necrosectomy versus Step up Approach) randomized controlled trial of conventional versus minimally invasive debridement for infected pancreatic necrosis. This trial is only the second randomized controlled trial of treatment for pancreatic necrosis and should encourage other specialists to follow suit. 31. Aultman DF, Bilton BD, Zibari GB, et al.: Nonoperative therapy for acute necrotizing pancreatitis. Am Surg 1997, 63:1114–1117. 32. Freeny PC, Hauptmann E, Althaus SJ, et al.: Percutaneous CT- guided catheter drainage of infected acute necrotising pancreatitis. Techniques and results. AJR Am J Roentgenol 1998, 170:969–975. 33. Baril NB, Ralls PW, Wren SM, et al.: Does an infected peripancreatic fluid collection or abscess mandate operation? Ann Surg 2000, 231:361–367. 34. Ammori BJ: Laparoscopic transgastric pancreatic necrosectomy for infected pancreatic necrosis. Surg Endosc 2000, 231:361–367. 35. Haan JM, Scalea TM: Laparoscopic debridement of recurrent pancreatic abscesses in the hostile abdomen. Am Surg 2002, 16:1362. 36.• Parekh D: Laparoscopic-assisted pancreatic necrosectomy. A new surgical option for treatment of severe necrotizing pancreatitis. Arch Surg 2006, 141:895–903. Despite the inevitable march toward nonsurgical intervention in infected pancreatic necrosis, here is one surgeon trying to make technical improvements in surgical debridement. Merging the skills of open and laparoscopic approaches is a paradigm for encouraging pancreatologists to consider a similar merging of skills that are currently craft specific. 37. Gagner M: Laparoscopic treatment of acute necrotizing pancreatitis. Semin Laparosc Surg 2006, 3:10–14. 38. 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. 39. Connor S, Alexakis N, Raraty MG, et al.: Early and late complications after pancreatic necrosectomy. Surgery 2005, 137:499–505. 40. Mui LM, Wong SK, Ng EK, et al.: Combined sinus tract endoscopy and endoscopic retrograde cholangiopancreatography in management of pancreatic necrosis and abscess. Surg Endosc 2005, 19:393–397. 41. Baron TH, Thaggard WG, Morgan DE, et al.: Endoscopic therapy for organized pancreatic necrosis. Gastroenterology 1996, 111:755–764. 42. Seifert H, Wehrmann T, Schmitt T, et al.: Retroperitoneal endoscopic debridement for infected peripancreatic necrosis. Lancet 2000, 356:653–655.
43.•• Seewald S, Groth S, Omar S, et al.: Aggressive endoscopic therapy for pancreatic necrosis and pancreatic abscess: a new safe and effective treatment algorithm (videos). Gastrointest Endosc 2005, 62:92–100. The reprint contains some excellent explanatory images and is accompanied by video footage. The authors clearly like a challenge: the term aggressive is well selected to emphasize the enthusiasm and commitment of the authors, perhaps in emulation of the careful but thorough surgical debridement. 44. Kozarek RA: Endoscopic management of pancreatic necrosis: not for the uncommitted. Gastrointest Endosc 2005, 62:101–104. 45. Charnley RM, Lochan R, Gray H, et al.: Endoscopic necrosectomy as primary therapy in the management of infected pancreatic necrosis. Endoscopy 2006, 38:925–928. 46. Raczynski S, Teich N, Borte G, et al.: Percutaneous transgastric irrigation drainage in combination with endoscopic necrosectomy in necrotizing pancreatitis (with videos). Gastrointest Endosc 2006, 64:420–424. 47.• Voermans RP, Veldkamp MC, Rauws EA, et al.: Endoscopic transmural debridement of organized pancreatic necrosis: a retrospective analysis. Gastrointest Endosc 2007, 66:909–916. Benefits from superb images and a continuing medical education video. The double percutaneous endoscopic gastrostomy technique is best understood by reference to the illustrations. The threedimensional CT reconstruction is particularly fascinating. 48.•• Papachristou GI, Takahashi N, Chahal P, et al.: Peroral endoscopic drainage/debridement of walled-off pancreatic necrosis. Ann Surg 2007, 245:943–951. An outstanding read. Despite criticisms over the diversity of case material and the adjuvant approaches that now seem to be required, this paper represents a decade of experience in trying to improve a less invasive intervention. There is an acknowledgment that this technique could usefully be combined with other new interventions, which appears to represent the best way forward for patients. 49. Lee JK, Kwak KK, Park JK, et al.: The efficacy of nonsurgical treatment of infected pancreatic necrosis. Pancreas 2007, 34:399–404. 50. Howard TJ, Temple MB: Prophylactic antibiotics alter the bacteriology of infected necrosis in severe acute pancreatitis. J Am Coll Surg 2002, 195:759–767. 51.• Banks PA, Freeman ML; Practice Parameters Committee of the American College of Gastroenterology: Practice guidelines in acute pancreatitis. Am J Gastroenterol 2006, 101:2379–2400. An excellent reference source that covers many aspects of pancreatic necrosis. There is a clear indication of the reliability of evidence cited in support of each recommendation, and the authors acknowledge where contrasting views on particular topics exist.
