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Evidence - Necrosectomy and continuous closed irrigation in infected hemorrhagic-necrotizing pancreatitis

  1. Summary of the Literature

    Acute pancreatitis is a potentially life-threatening condition, characterized morphologically by the interstitial edematous and necrotizing forms. Due to local and systemic complications as well as accompanying organ failure, mild, moderate, and severe courses are differentiated. The classification of severity is based on the revised Atlanta classification.

    The Revised Atlanta Classification 2012

    Classification and definition of acute pancreatitis were based until a few years ago on the Atlanta classification from 1992 [1], which was fundamentally revised between 2007 and 2012 by 11 international pancreatic expert commissions and published in 2013 [2]. The special feature of the revised classification is the redefinition of local complications and the clear definition of severity.

    According to the Atlanta classification 2012, the diagnosis of acute pancreatitis can be made if 2 of the following 3 criteria are met:

    1. Abdominal pain typical of the disease (e.g., severe girdle-like upper abdominal pain, often radiating to the back)

    2. Elevation of serum lipase (also amylase) > 3 times the upper normal limit

    3. Characteristic imaging findings (contrast-enhanced CT, MRI, or ultrasound)

    The early and late phases of the disease are distinguished:

    Early phase

    • First week of the disease, where the systemic response to pancreatitis is predominant.

    Late phase

    • Persistence of systemic reactions or presence of local complications, which can last weeks to months.

    Two forms of acute pancreatitis are distinguished:

    1. Interstitial edematous form

    • Inflammation is limited to the pancreatic parenchyma and surrounding tissue
    • No necrosis

    2. Necrotizing form

    • Parenchymal necrosis and/or peripancreatic necrosis

    Three severity grades of acute pancreatitis are defined:

    1. Mild acute pancreatitis

    • No organ failure
    • No local or systemic complications

    2. Moderately severe acute pancreatitis

    • Transient organ failure < 48 h
    • Local and/or systemic complications (without organ failure)

    3. Severe acute pancreatitis

    • Persistent organ failure > 48 h (single or multiple organ failure)
    • Not necessarily required for definition: local complications (but usually present)

    Definition of complications of acute pancreatitis:

    1. Local complications

    • APFC, acute peripancreatic fluid collection: acute peripancreatic fluid collections in interstitial edematous pancreatitis without necrosis, within the first 4 weeks, no formation of pseudocysts
    • Pancreatic pseudocysts; encapsulated fluid with an inflammatory wall without necrosis or at most minimal necrosis formation; arise after the 4th week of edematous interstitial pancreatitis
    • ANC, acute necrotic collection: accumulation of fluid and necrosis without capsule in the early phase, affecting pancreatic parenchyma and/or peripancreatic tissue
    • WON, walled-off necrosis: encapsulated necrosis; (peri)pancreatic necrosis with a well-defined capsule, which arises no earlier than 4 weeks after the onset of the disease
    • Infected necrosis

    2. Systemic complications

    Exacerbation of pre-existing diseases, e.g., CAD, COPD – does not count as organ failure!

    3. Organ failure

    Pulmonary, cardiovascular, and renal systems are evaluated according to the modified Marshall score [3].

    Fluid collections and necrosis occur within 4 weeks of the onset of acute pancreatitis, while pseudocysts and WON can only be detected > 4 weeks after the onset of pancreatitis. Additionally, up to 50% of cases of necrotizing pancreatitis may develop thrombosis in the splanchnic circulation (portal vein, mesenteric vein, splenic vein) [4].

    A study published in 2016 compared the original Atlanta classification from 1992 with the revised version from 2012. The study showed that the original classification performed significantly worse than the revised form, particularly in terms of stratification for the necessity and duration of intensive care treatment as well as for the indication of surgical intervention [5].

    Imaging

    The onset and time interval of the different stages (early and late phase) are determined by the onset of symptoms, which is why a detailed history is important. If laboratory findings and clinical presentation match the diagnosis of acute pancreatitis, a contrast-enhanced CT is not necessarily required upon patient admission. A contrast-enhanced CT should only be performed upon admission in cases of diagnostic uncertainty (differential diagnosis, e.g., abscess, hollow organ perforation) or if there is already suspicion of local complications at this time (early phase does not mean that no local complications can occur).

    CT allows risk stratification by distinguishing between edematous and necrotizing pancreatitis and should be performed no earlier than 72 - 96 hours after symptom onset, but preferably after 5 - 7 days, as the CT is most informative then. It should be noted that the extent of necrosis does not have to be proportional to the severity of the disease. MRI is a diagnostic procedure comparable to CT.

    The transabdominal ultrasound examination is the standard procedure in the imaging diagnosis of acute pancreatitis and should be performed on every patient with acute pancreatitis. In addition to visualizing the pancreas itself, other differential diagnoses are usually well delineated, e.g., cholecystitis or nephrolithiasis. Cholecystitis or cholestasis can also provide clues to biliary pancreatitis.

    A review compared the need for simple but meaningful scores regarding the severity of acute pancreatitis. The BISAP score (Bedside index of severity in acute pancreatitis) and the HAPS score (Harmless acute pancreatitis score) were considered helpful. However, the modified Marshall score (A definition of organ failure in acute pancreatitis), recommended in the revised version of the Atlanta classification, was not compared [6].

    Therapeutic Aspects

    In the treatment of acute pancreatitis, an early and late treatment phase can be distinguished in principle. In the early phase, circulatory stabilization, support of organ function, and pain therapy are the focus, while in the late phase, the treatment of infections and the sanitation of necrosis are the focus.

    The same criteria that apply to other severe internal diseases are generally suitable for the indication for admission to the intensive care unit. The following scores can be helpful for the decision on intensive care management:

    • SIRS = Systemic Inflammatory Response Syndrome
    • APACHE II = Estimate mortality in the critically ill
    • SOFA = Sequential Organ Failure Assessment

    The guidelines of the American College of Gastroenterology contain various patient characteristics that indicate an increased risk for a severe course of acute pancreatitis [7]. The guidelines of the International Association of Pancreatology (IAP)/American Pancreatic Association (APA) recommend intensive care monitoring for every patient with severe acute pancreatitis according to the Atlanta classification [8].

    Depending on the etiology of acute pancreatitis, causal therapy must be considered early. If acute biliary pancreatitis with cholangitis is present, an ERCP should be performed within 24 hours to sanitize the infection focus [8, 9], without cholangitis within 72 hours. A cholecystectomy should be performed during the same hospital stay, which is also safe in the context of a necrosectomy [10]. Early cholecystectomy shows no increased risks compared to late elective cholecystectomy [11]. A review from 2012 showed that delayed cholecystectomy led to a higher rate of hospital readmissions [12].

    In the late phase of severe acute pancreatitis, pseudocysts or encapsulated necrotic areas may develop. Pseudocysts can compromise adjacent structures such as the duodenum as they grow, they can become infected and bleed. Therefore, if symptoms are present, endosonographic cyst puncture with nasocystic drainage is recommended [13].

    Necrosis in the pancreatic and peripancreatic tissue can occur in the early phase as ANC (non-encapsulated necrosis) and in the late phase as WON (necrosis with wall structure). In about 1/3 of cases, necrosis becomes infected, which is associated with increased mortality and therefore requires intervention [14]. Infection of necrosis predominantly occurs only 2 weeks after the onset of the disease [15]. An interventional therapy of infected necrosis should be performed as late as possible, ideally > 4 weeks, when a defined wall structure is distinguishable. Early intervention is both technically more difficult and associated with an increased complication rate (e.g., bleeding, hollow organ perforation) [16]. Therefore, early intervention should only be performed in cases of increasing clinical instability or sepsis. The standard therapy for infected necrosis until the formation of a wall structure is drainage and administration of anti-infectives [16]. Retrospective analyses show that early drainage can reduce the indication for definitive necrosectomy [17].

    Intervention in necrosis should generally follow a minimally invasive step-up approach: antibiotics -> drainage -> if necessary, necrosectomy [16]. In about 30% of cases, drainage alone is sufficient; with WON, solid necrotic material is usually present, so additional necrosectomy is required [18]. As an endoscopic maneuver, endosonographic puncture with transgastric or transduodenal placement of a drainage using self-expanding metal stents and subsequent endoscopic necrosectomy through the existing access is considered. The step-up procedure can be performed surgically with sonographically or CT-guided percutaneous drainage placement and subsequent minimally invasive necrosectomy (video-assisted retroperitoneal debridement = VARD).

    The minimally invasive step-up procedure causes fewer complications, organ failure, and also costs compared to open necrosectomy [19, 20, 21].

    A meta-analysis from 2015 showed that although antibiotic prophylaxis is not generally recommended for acute pancreatitis, mortality in patients with severe acute pancreatitis can be significantly reduced with prophylaxis [22].

  2. Currently ongoing studies on this topic

  3. Literature on this Topic

    1. Bradley EL, III. (1993) 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;128(5):586–590

    2. Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, Tsiotos GG, Vege SS (2013) Acute Pancreatitis Classification Working G. Classification of acute pancreatitis– 2012: revision of the Atlanta classification and definitions by international consensus. Gut 62(1):102–111

    3. Marshall JC, Cook DJ, Christou NV, et al. Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome. Crit Care Med 1995;23:1638-52.

    4. Nadkarni NA, Khanna S, Vege SS (2013) Splanchnic venous thrombosis and pancreatitis. Pancreas 42:924–931

    5. Bansal SS, Hodson J, Sutcliffe RS, Marudanayagam R, Muiesan P, Mirza DF, Isaac J, Roberts KJ (2016) Performance of the revised Atlanta and determinant-based classifications for severity in acute pancreatitis. Br J Surg 103(4):427–433

    6. Kuo DC, Rider AC, Estrada P, Kim D, Pillow MT (2015) Acute Pancreatitis: What's the Score? J Emerg Med 48(6):762–770

    7. Tenner S, Baillie J, Dewitt J et al (2013) American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol 108:1400–1415

    8. Working Group (2013) IAP/APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology 13:e1–15

    9. Tenner S, Baillie J, Dewitt J et al (2013) American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol 108:1400–1415

    10. Da Costa DW, Bouwense SA, Schepers NJ et al (2015) Same admission versus interval cholecystectomy for mild gallstone pancreatitis (PONCHO): a multicenter randomized controlled trial. Lancet 386:1261–1268

    11. Gurusamy KS, Nagendran M, Davidson BR (2013) Early versus delayed laparoscopic cholecystectomy for acute gallstone pancreatitis. Cochrane Database Syst Rev 2013(9):CD010326

    12. van Baal MC, Besselink MG, Bakker OJ, van Santvoort HC, Schaapherder AF, Nieuwenhuijs VB, Gooszen HG, van Ramshorst B, Boerma D, Dutch Pancreatitis Study G (2012) Timing of cholecystectomy after mild biliary pancreatitis: a systematic review. Ann Surg 255(5):860–866

    13. Gurusamy KS, Pallari E, Hawkins N, Pereira SP, Davidson BR (2016b) Management strategies for pancreatic pseudocysts. Cochrane Database Syst Rev 2016;4:CD011392

    14. Boumitri C, Brown E, Kahaleh M (2017) Necrotizing Pancreatitis: Current Management and Therapies. Clin Endosc 50:357–365

    15. Forsmark CE, Vege SS, Wilcox CM (2016) Acute Pancreatitis. N Engl J Med 375:1972–1981

    16. Van Grinsven J, Van Santvoort HC, Boermeester MA et al (2016) Timing of catheter drainage in infected necrotizing pancreatitis. Nat Rev Gastroenterol Hepatol 13:306–312

    17. Van Grinsven J, Timmerman P, Van Lienden KP et al (2017) Proactive Versus Standard Percutaneous Catheter Drainage for Infected Necrotizing Pancreatitis. Pancreas 46:518–523

    18. Van Santvoort HC, Besselink MG, Bakker OJ et al (2010) A step-up approach or open necrosectomy for necrotizing pancreatitis. N Engl J Med 362:1491–1502

    19. Gurusamy KS, Belgaumkar AP, Haswell A, Pereira SP, Davidson BR (2016a) Interventions for necrotizing pancreatitis. Cochrane Database Syst Rev 4:CD011383

    20. van Santvoort HC, Besselink MG, Bakker OJ, Hofker HS, Boermeester MA, Dejong CH, van GH, Schaapherder AF, van Eijck CH, Bollen TL, van RB, Nieuwenhuijs VB, Timmer R, Lameris JS, Kruyt PM, Manusama ER, van der Harst E, van der Schelling GP, Karsten T, Hesselink EJ, van Laarhoven CJ, Rosman C, Bosscha K, de Wit RJ, Houdijk AP, van Leeuwen MS, Buskens E, Gooszen HG (2010) A step-up approach or open necrosectomy for necrotizing pancreatitis. N Engl J Med 362(16):1491–1502

    21. Li A, Cao F, Li J, Fang Y, Wang X, Liu DG, Li F (2016) Step-up mini-invasive surgery for infected pancreatic necrosis: Results from prospective cohort study. Pancreatology 16(4):508–514

    22. Lim CL, Lee W, Liew YX, Tang SS, Chlebicki MP, Kwa AL (2015) Role of antibiotic prophylaxis in necrotizing pancreatitis: a meta-analysis. J Gastrointest Surg 19(3):480–491

  4. Reviews

    Gjeorgjievski M, Bhurwal A, Chouthai AA, Abdelqader A, Gaidhane M, Shahid H, Tyberg A, Sarkar A, Kahaleh M. Percutaneous endoscopic necrosectomy (PEN) for treatment of necrotizing pancreatitis: a systematic review and meta-analysis. Endosc Int Open. 2023 Mar 23;11(3):E258-E267.

    He K, Gao L, Yang Z, Zhang Y, Hua T, Hu W, Wu D, Ke L. Aggressive versus controlled fluid resuscitation in acute pancreatitis: A systematic review and meta-analysis of randomized controlled trials. Chin Med J (Engl). 2023 May 20;136(10):1166-1173

    Khizar H, Zhicheng H, Chenyu L, Yanhua W, Jianfeng Y. Efficacy and safety of endoscopic drainage versus percutaneous drainage for pancreatic fluid collection; a systematic review and meta-analysis. Ann Med. 2023 Dec;55(1):2213898.

    Liu Z, Liu P, Xu X, Yao Q, Xiong Y. Timing of minimally invasive step-up intervention for symptomatic pancreatic necrotic fluid collections: A systematic review and meta-analysis. Clin Res Hepatol Gastroenterol. 2023 Apr;47(4):102105.

    Niu CG, Zhang J, Zhu KW, Liu HL, Ashraf MF, Okolo PI 3rd. Comparison of early and late intervention for necrotizing pancreatitis: A systematic review and meta-analysis. J Dig Dis. 2023 May;24(5):321-331.

    Yang Y, Zhang Y, Wen S, Cui Y. The optimal timing and intervention to reduce mortality for necrotizing pancreatitis: a systematic review and network meta-analysis. World J Emerg Surg. 2023 Jan 27;18(1):9.

    Zhu L, Shen J, Fu R, Lu X, Du L, Jiang R, Zhang M, Shi Y, Jiang K, Shi Y. Early versus Delayed Minimally Invasive Intervention for Acute Necrotizing Pancreatitis: An Updated Systematic Review and Meta-Analysis. Dig Surg. 2022;39(5-6):224-231.

  5. Guidelines

  6. literature search

    Literature search on the pages of pubmed.