Current managements of Infected necrotizing pancreatitis Clinical courses

  • Slides: 72
Download presentation
Current managements of Infected necrotizing pancreatitis 보라매 소화기내과 정지봉

Current managements of Infected necrotizing pancreatitis 보라매 소화기내과 정지봉

Clinical courses of acute pancreatitis https: //www. google. com/search? source=lnms&tbm

Clinical courses of acute pancreatitis https: //www. google. com/search? source=lnms&tbm

Example of management algorithm for necrotizing pancreatitis da Costa, D. W. et al. Br.

Example of management algorithm for necrotizing pancreatitis da Costa, D. W. et al. Br. J. Surg, 2014

TENSION trial (Transluminal endoscopic step-up approach versus minimally invasive surgical stepup approach in patients

TENSION trial (Transluminal endoscopic step-up approach versus minimally invasive surgical stepup approach in patients with infected necrotising pancreatitis) MISER trial (Necrotizing Pancreatitis; Minimally Invasive Surgery Versus Endoscopy Randomized)

New different points, compared with previous study? • TENSION trial in Lancet (2018) -

New different points, compared with previous study? • TENSION trial in Lancet (2018) - The endoscopic step-up approach is not superior to the surgical step-up approach in reducing major complications or mortality. - The incidence of pancreatic fistula and the duration of hospital stay were lower in the endoscopic arm. • MISER trial in Gastroenterology (2019) -An endoscopic approach for infected necrotizing pancreatitis, compared with minimally invasive surgery, significantly reduced major complications, lowered costs, and increased quality of life.

TENSION trial(2018) MISER trial(2019) Study design National wide(19 hospitals, Netherlands) Single center(Florida hospital, USA)

TENSION trial(2018) MISER trial(2019) Study design National wide(19 hospitals, Netherlands) Single center(Florida hospital, USA) Duration 2011 -2015 2014 -2017 Patient pool 418 pts with pancreatic/extrapancreatic necrosis 168 pts with acute necrotizing pancreatitis Endoscopic Surgical No of patent 51 47 34 32 Major complication or Death 22(43%) 21(45%) 0. 88 4(11. 8%) 13(40. 6%) 0. 007 Death 9(18%) 6(13%) 0. 5 3(8. 8%) 2(6. 3%) 0. 999 Definition of major complications New-onset organ failure, bleeding, perforation, incisional hernia, EC fistula(requiring intervention) pancreatic fistula as other endpoints 2/42(5%) 13/41(32%) P value New-onset organ failure/systemic dysfx, enteralpancreatic cutaneous fistula, peforation, bleeding, enteral-pancreatic cutaneous fistula 0. 0011 Enteral-pancreatic cutaneous fistula as major complication 0 9(28. 1%) 0. 001 16. 5 d 23. 3 d 0. 057 $ 75, 830 $ 117, 492 0. 039 Length of hospital stay -Days in hospital within 6 months of randomization 53 d 69 d 0. 014 -Length of hospital stay_index intervention to discharge. Mean total cost Quality of life at 3 -mon f/u(PCS) € 60, 228 € 73, 883 No sig 5. 29 0. 039

TENSION trial(2018) MISER trial(2019) Study design Nationalwide(19 hospitals, Netherlands) Single center(Florida hospital, USA) Duration

TENSION trial(2018) MISER trial(2019) Study design Nationalwide(19 hospitals, Netherlands) Single center(Florida hospital, USA) Duration 2011 -2015 2014 -2017 Patient pool 418 pts with pancreatic/extrapancreatic necrosis 168 pts with acute necrotizing pancreatitis Endoscopic Surgical No of patent 51 47 34 32 Major complication or Death 22(43%) 21(45%) 0. 88 4(11. 8%) 13(40. 6%) 0. 007 Death 9(18%) 6(13%) 0. 5 3(8. 8%) 2(6. 3%) 0. 999 Definition of major complications New-onset organ failure, bleeding, perforation, incisional hernia, EC fistula(requiring intervention) pancreatic fistula as other endpoints 2/42(5%) 13/41(32%) P value New-onset organ failure/systemic dysfx, enteralpancreatic cutaneous fistula, peforation, bleeding, enteral-pancreatic cutaneous fistula 0. 0011 Enteral-pancreatic cutaneous fistula as major complication 0 9(28. 1%) 0. 001 16. 5 d 23. 3 d 0. 057 $ 75, 830 $ 117, 492 0. 039 Length of hospital stay -Days in hospital within 6 months of randomization 53 d 69 d 0. 014 -Length of hospital stay_index intervention to discharge. Mean total cost Although enteral Quality of life at 3 -mon f/u(PCS) € 60, 228 € 73, 883 and pancreatic-cutaneous fistulae can lead to significant morbidity, they are not lifethreatening complications. No sig 5. 29 0. 039

IN TENSION trial Endoscopic approach with double pig tail stents and nasocystic drainage ->if

IN TENSION trial Endoscopic approach with double pig tail stents and nasocystic drainage ->if clinically unsuccessful ->endoscopic necrosectomy First, PCD (percutaneous catheter drainage) *22(43%) pts: treated with catheter drainage only *24(51%) pts; treated with PCD drainage only ->if clinically unsuccessful ->VARD(video-assisted retroperitoneal debridement)

Is a fair game by a member of TENSION group? In MISER trial (n=35)

Is a fair game by a member of TENSION group? In MISER trial (n=35) (n=34) * PCD ->not required -> selection bias - 14/34 (41%) of pts: PCD prior to intervention -> decrease risk of new onset SIRS, compared with surgical approach. - All pts with nasocystic drain (n=32) - 9/32 (28%) of pts: PCD prior to intervention - The remaining -> surgical approach was performed directly Boxhoorn et al. Gastroenterology, 2019, as comment letter

Is a fair game by a member of TENSION group? In MISER trial N=34

Is a fair game by a member of TENSION group? In MISER trial N=34 N=32 For inclusion of only critically ill patients Previous research showed that 40%– 50% of patients with infected NP can be treated by catheter drainage alone and do not require a necrosectomy Boxhoorn et al. Gastroenterology, 2019, as comment letter

F/U to 6 m F/U to 7 y

F/U to 6 m F/U to 7 y

Long-term results following a intervention to infected NP? • Endocrine insufficiency - n=1102 -

Long-term results following a intervention to infected NP? • Endocrine insufficiency - n=1102 - Meta-analysis - Prevalence of newly diagnosed diabetes is much higher after acute pancreatitis (23%) than the prevalence of diabetes in the general population (4– 9%). Das et al. Gut, 2013 • Exocrine insufficiency - n=1495 - Meta-analysis - After acute pancreatitis, a quarter of all patients develop PEI during follow-up. Hollemans et al. Pancreatology, 2018

Why? • The step-up approach may preserve pancreatic parenchyma and function, as compared with

Why? • The step-up approach may preserve pancreatic parenchyma and function, as compared with primary open necrosectomy. • This effect of step-up approach becomes apparent shortly after recovery of the disease and keeps constant during the long-term f/u

Conclusion • Endoscopic debridement is new standard option in the management of infected necrotizing

Conclusion • Endoscopic debridement is new standard option in the management of infected necrotizing pancreatitis. • There are no differences in major complications/death between endoscopic step-up approach and minimal invasive surgical approach. • But, endoscopic step-up approach has some advantages in reducing length of hospital stay and surgical complications, such as pancreatic fistula • Minimally invasive step-up surgical approach has some advantages in terms of less pancreatic exocrine insufficiency and trend towards less endocrine insufficiency, compared with open necrosectomy.

Although enteral and pancreatic-cutaneous fistulae can lead to significant morbidity, they are not lifethreatening

Although enteral and pancreatic-cutaneous fistulae can lead to significant morbidity, they are not lifethreatening complications.

MISER trial TENSION trial

MISER trial TENSION trial

MISER trial TENSION trial

MISER trial TENSION trial

Endoscopic vs surgical step-up • endoscopic catheter drainage followed by endoscopic necrosectomy (if necessary)

Endoscopic vs surgical step-up • endoscopic catheter drainage followed by endoscopic necrosectomy (if necessary) vs percutaneous catheter drainage followed by VARD (if necessary) • Similar mortality/morbidity rate • Lower CV organ failure (6% vs 19%) • Fewer pancreatic fistula (5% vs 32%) • Shorter hospital stay (by 16 days)

Classification of AP https: //www. google. com/search? q=necrotizing+pancreatitis&tbm

Classification of AP https: //www. google. com/search? q=necrotizing+pancreatitis&tbm

Minimal invasive vs open approach • minimal approach> open approach in effectiveness • PANTER

Minimal invasive vs open approach • minimal approach> open approach in effectiveness • PANTER trial in NEJM(2010) • In Netherlands • Prospective randomized trial • n=88 Minimally invasive step-up approach reduces major Cx and mortality in infected necrotizing pancreatitis, compared with primary open necrosectomy. • Pooled analysis of 1980 pts from 15 cohorts in Gut(2018) • In international • 51 hospitals; 8 countries • N=1980 • Meta Pooled analysis from 15 cohorts • minimally invasive surgical and endoscopic necrosectomy are associated with reduced death rates compared with open necrosectomy. • Retrospective of 394 pts in Ann Surg(2016) • In UK, single center in Liverpool) • The role of MARPN in reducing complications and deaths within a multimodality approach remains substantial and should be used initially if feasible • Multicenter trail in German in PLo. S(2016) • In The German Pancreatitis Study Group performed a multicenter, retrospective study • 220 pts • A step-up approach starting with minimal invasive drainage techniques and endoscopic necrosectomy results in a significant reduction of morbidity and mortality in necrotising pancreatitis compared to a primarily surgical intervention.

Endoscopic vs surgical step-up • TENSION trial in Lancet(2017) • The endoscopic step-up approach

Endoscopic vs surgical step-up • TENSION trial in Lancet(2017) • The endoscopic step-up approach is not superior to the surgical step-up approach in reducing serious complications or mortality. • The incidence of pancreatic fistula and the duration of hospital stay were lower in the endoscopic arm.

Terminolgoy of AP (I) • Necrotizing pancreatitis - Lack of parenchymal enhancement by iv

Terminolgoy of AP (I) • Necrotizing pancreatitis - Lack of parenchymal enhancement by iv contrasts on CT • Acute necrotic collection (ANC), <4 wks - Heterogeneous and non-liquid density - No definable wall structure • - Walled-off necrosis (WON), >4 wks Heterogeneous with liquid and non-liquid density Well defined wall structure Occurs >4 weeks after onset of necrotizing pancreatitis. revisions of the Atlanta classification and definitions by international consensus. Gut 2013

Terminolgoy of AP (II) • Necrotizing pancreatitis - Lack of parenchymal enhancement by iv

Terminolgoy of AP (II) • Necrotizing pancreatitis - Lack of parenchymal enhancement by iv contrasts on CT • Acute necrotic collection (ANC), <4 weeks - Heterogeneous and non-liquid density - No definable wall structure • Walled-off necrosis (WON), >4 weeks - Heterogeneous with liquid and non-liquid density (some may appear homogenous) - Well defined wall structure - Occurs >4 weeks after onset of necrotizing pancreatitis. revisions of the Atlanta classification and definitions by international consensus. Gut 2013

Terminolgoy of AP (III) • Infected pancreatic necrosis - Extraluminal gas in the pancreatic/peripancreatic

Terminolgoy of AP (III) • Infected pancreatic necrosis - Extraluminal gas in the pancreatic/peripancreatic tissues on CECT - Percutaneous, image-guided, fine-needle aspiration (FNA) is positive for bacteria/fungi on Gram stain and culture

Severity of acute pancreatitis • Scoring system

Severity of acute pancreatitis • Scoring system

Severity of acute pancreatitis SOCIETY GUIDELINES • International Association of Pancreatology (IAP)/ American Pancreatic

Severity of acute pancreatitis SOCIETY GUIDELINES • International Association of Pancreatology (IAP)/ American Pancreatic Association (APA)

 • American College of Gastroenterology (ACG)

• American College of Gastroenterology (ACG)

Society guideline links: Acute pancreatitis_I • International • ●International Association of Pancreatology (IAP)/American Pancreatic

Society guideline links: Acute pancreatitis_I • International • ●International Association of Pancreatology (IAP)/American Pancreatic Association (APA): Evidence-based guidelines for the management of acute pancreatitis (2013) • ●International Consensus Guideline Committee (ICGC): International consensus guidelines for nutrition therapy in pancreatitis(2012) • ●American Thoracic Society (ATS), European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), Society of Critical Care Medicine (SCCM), and the Société de Réanimation de Langue Française (SRLF): Management of the critically ill patient with severe acute pancreatitis (2004) • United States • ●American Society for Gastrointestinal Endoscopy (ASGE): Guideline on adverse events associated with ERCP (2017) • ●Choosing Wisely: Do not test for amylase in cases of suspected acute pancreatitis. Instead, test for lipase (2016) • ●ASGE: Guideline on the role of endoscopy in benign pancreatic disease (2015) • ●American College of Gastroenterology (ACG): Guideline for the management of acute pancreatitis (2013) • ●American College of Radiology (ACR): ACR Appropriateness Criteria acute pancreatitis (1998, revised 2013) • ●International Association of Pancreatology (IAP)/American Pancreatic Association (APA): Evidence-based guidelines for the management of acute pancreatitis (2013) • ●American Gastroenterological Association (AGA): Medical position statement on acute pancreatitis (2007) • ●American Thoracic Society (ATS), European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), Society of Critical Care Medicine (SCCM), and the Société de Réanimation de Langue Française (SRLF): Management of the critically ill patient with severe acute pancreatitis (2004) • ●Society for Surgery of the Alimentary Tract (SSAT): Patient care guidelines for the treatment of acute pancreatitis (1996, revised 2004) • Europe • ●European Society of Gastrointestinal Endoscopy (ESGE): Guideline on prophylaxis of post-ERCP pancreatitis, update (2014) • ●European Society of Clinical Nutritional and Metabolism (ESPEN): Guidelines on parenteral nutrition – Pancreas (2009) • ●ESPEN: Guidelines on enteral nutrition – Pancreas (2006) • ●American Thoracic Society (ATS), European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), Society of Critical Care Medicine (SCCM), and the Société de Réanimation de Langue Française (SRLF): Management of the critically ill patient with severe acute pancreatitis (2004)

Society guideline links: Acute pancreatitis_II • United Kingdom • ●National Institute for Health and

Society guideline links: Acute pancreatitis_II • United Kingdom • ●National Institute for Health and Care Excellence (NICE): Interventional procedures guidance on endoscopic transluminal pancreatic necrosectomy (2016) • ●NICE: Interventional procedures guidance on percutaneous retroperitoneal endoscopic necrosectomy (2011) • ●British Society of Gastroenterology (BSG): UK guidelines for the management of acute pancreatitis (2005) • Japan • ●[In Japanese] Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS): Revisions in the 2015 Japanese guidelines for the management of acute pancreatitis – Medical treatments (published 2016) • • [In Japanese] JSHBPS: Acute pancreatitis clinical practice guidelines, 4 th edition (2015) • ●[In Japanese] Diagnosis/treatment consensus for local pancreatitis complications (pancreatic pseudocyst, infectious encapsulation necrosis, etc), 2014 (published 2015) • ●[In Japanese]: Japanese Pancreatic Society (JPS): Acute pancreatitis clinical practice guideline, 4 th edition (2015) • ●[In Japanese] JPS: Post-ERCP pancreatitis guideline (2015) • ●[In English] JSHBPS: Revised Japanese guidelines for the management of acute pancreatitis – Revised concepts and updated points (2015) • • [In English] JSHBPS: Japanese guidelines for the management of acute pancreatitis (2015) • ●[In English] Consensus of primary care in acute pancreatitis in Japan (2006) • ●[In English] Japanese Society of Emergency Abdominal Medicine (JSEAM) and JPS: JPN guidelines for the management of acute pancreatitis (2006)

Percutaneous catheter drainage • Mechanisms: decompress retroperitoneal fluid collections and allow stabilization of patients

Percutaneous catheter drainage • Mechanisms: decompress retroperitoneal fluid collections and allow stabilization of patients with sepsis prior to formal operative debridement • Follows-up with contrast CT scan: to assess the removal of necrotic debris and changes in the cavity dimension, and ensure catheter lumen patency • Percutaneous catheter drainage as bridging technique: Especially, in patient who are unstable to undergo surgical debridement 1/3 of patients can be managed with percutaneous drainage alone Traverso LW et al. J Gastrointest Surg 2005 Freeny PC et al. AJR Am J Roentgenol 1998 Mortelé KJ et al. Am J Roentgenol 2009

Minimally invasive approach (ex: video-assisted retroperitoneal debridement(VARD)) • PANTER study - PCD followed by

Minimally invasive approach (ex: video-assisted retroperitoneal debridement(VARD)) • PANTER study - PCD followed by VARD vs. open pancreatic debridement - Decreased the rate of MOF, incisional hernia, and new-onset DM - Did not significantly affect mortality. Besselink MG et al. BMC Surg 2006 van Santvoort HC et al. N Engl J Med 2010

Endoscopic debridement • Limited to patients with WON in previous studies Papachristou et al.

Endoscopic debridement • Limited to patients with WON in previous studies Papachristou et al. Ann Surg 2007 Navaneethan et al. Pancreas 2009 Bradley EL 3 rd et al. J Gastrointest Surg 2008 • Double pigtail plastic catheters (traditional) -> lumen-apposing metal stents with wider diameters to facilitate drainage (ongoing) • Serial abdominal CT scans, every 1 or 2 wks after the intervention • Reinterventions, based upon CT imaging and clinical response • Reduction in the systemic inflammatory response and avoidance of pancreatic fistula • In meta-analysis, 69% success rate, 34% morbidity rate, and 2% mortality rate 1/3 of pts treated with endoscopic debridement ultimately need open surgical debridement Bradley EL 3 rd et al. Ann Surg 2010 Bradley EL 3 rd et al. J Gastrointest Surg 2008

Endoscopic vs surgical step-up https: //www. youtube. com/watch? v=Agl_Dj. MOi 38 da Costa, D.

Endoscopic vs surgical step-up https: //www. youtube. com/watch? v=Agl_Dj. MOi 38 da Costa, D. W. et al. Br. J. Surg, 2014

Which patients has the risk of additional necrosectomy after drainage? • Male, MOF, extent

Which patients has the risk of additional necrosectomy after drainage? • Male, MOF, extent and heterogeneity of pancreatic necrosis • MOF, Mean CT density of necrosis This article Hollemans et al. Ann Surg. 2016 AUC= 0. 775

Conclusion • The optimal timing for pancreatic debridement is 3 to 4 weeks following

Conclusion • The optimal timing for pancreatic debridement is 3 to 4 weeks following the onset of acute pancreatitis • Step up approach (drainage and then, minimal invasive debridement) is new standard method in infected necrotizing pancreatitis, instead of traditional open pancreatic necrosectomy • Percutaneous catheter drainage is primarily a bridging technique for patients who are too unstable to undergo surgical debridement -> 1/3 of patients can be managed with percutaneous drainage alone. • Endoscopic debridement On clinical study Limited result in Dutch group -> generalization? Require endoscopic expert More validations are required If necessary, limited to patients with WON • MOF and Heterogeneity of necrosis can be considered as the risk factor of additional necrosectomy

 • Acute necrotic collection (ANC) • Heterogeneous and non-liquid density of varying degrees

• Acute necrotic collection (ANC) • Heterogeneous and non-liquid density of varying degrees in different locations (some appear homogeneous early in their course) • No definable wall encapsulating the collection • Walled-off necrosis (WON) • Heterogeneous with liquid and non-liquid density with varying degrees of loculations (some may appear homogeneous) • Well defined wall, that is, completely encapsulated • Maturation usually requires four weeks after onset of acute necrotizing pancreatitis • WON usually occurs >4 weeks after onset of necrotizing pancreatitis.

Severity assessment • During initial 24 hr • 추천 -> SIRS score(simple, cheap, readily

Severity assessment • During initial 24 hr • 추천 -> SIRS score(simple, cheap, readily available, accurate) • • contrast-enhanced CT f/u

Which patients has the risk of additional necrosectomy after drainage? • Male, MOF, extent

Which patients has the risk of additional necrosectomy after drainage? • Male, MOF, extent and heterogenous collection of pancreatic necrosis Hollemans et al. Ann Surg. 2016 • Reversal of sepsis within 1 wk of PCD, APACHE II score at the 1 st PCD, and OF within 1 wk after the onset of disease Babu et al. Ann Surg. 2013 • Mean CT density of necrosis, MOF, procalcitonin This article

https: //www. youtube. com/watch? v=Agl_Dj. MOi 38

https: //www. youtube. com/watch? v=Agl_Dj. MOi 38

https: //www. youtube. com/watch? v=Agl_Dj. MOi 38

https: //www. youtube. com/watch? v=Agl_Dj. MOi 38

https: //www. youtube. com/watch? v=Agl_Dj. MOi 38

https: //www. youtube. com/watch? v=Agl_Dj. MOi 38

https: //www. youtube. com/watch? v=Agl_Dj. MOi 38

https: //www. youtube. com/watch? v=Agl_Dj. MOi 38

https: //www. youtube. com/watch? v=Agl_Dj. MOi 38

https: //www. youtube. com/watch? v=Agl_Dj. MOi 38

https: //www. youtube. com/watch? v=Agl_Dj. MOi 38

https: //www. youtube. com/watch? v=Agl_Dj. MOi 38

https: //www. youtube. com/watch? v=Agl_Dj. MOi 38

https: //www. youtube. com/watch? v=Agl_Dj. MOi 38

https: //www. youtube. com/watch? v=Agl_Dj. MOi 38

https: //www. youtube. com/watch? v=Agl_Dj. MOi 38

https: //www. youtube. com/watch? v=Agl_Dj. MOi 38

https: //www. youtube. com/watch? v=Agl_Dj. MOi 38

 • Indications of Image-Guided Fine-Needle Aspiration • and Percutaneous Catheter Drainage (PCD) •

• Indications of Image-Guided Fine-Needle Aspiration • and Percutaneous Catheter Drainage (PCD) • Patients who did not improve on medical management in the • form of: • 1. Persisting fever • 2. Leukocytosis • 3. Worsening or new-onset organ failure • 4. Presence of gas in pancreatic bed

 • • • Indications of pancreatic necrosectomy: 1. Persistent/worsening sepsis after PCD: a.

• • • Indications of pancreatic necrosectomy: 1. Persistent/worsening sepsis after PCD: a. Persistently raised leukocyte count/increasing trend of leukocyte count b. Persistent/worsening organ failure or new-onset organ failure 2. Ongoing sepsis (definition in Table 1) 3. Inadequate drainage of collection and necrosis (definition in Table 1) 4. Failure to thrive (definition in Table 1) 5. Presence of ongoing necrosis with bowel complications (eg, necrosis, uncontrolled fistula, obstruction)

 • Criteria for Catheter Removal • 1. Catheter output of less than 10

• Criteria for Catheter Removal • 1. Catheter output of less than 10 milliliters per day of nonpurulent • fluid for 2 consecutive days (after adequate flushing and ensuring • the patency) with normal amylase levels • 2. No residual collection on a serial CT scan/ultrasonography (USG) • (Fig. 3) • 3. Clinical recovery, ie, no fever, accepting normal diet, gaining • weight, able to carry out routine activities

 • Primary Endpoints • 1. Sepsis reversal with PCD • 2. Proportion of

• Primary Endpoints • 1. Sepsis reversal with PCD • 2. Proportion of patients requiring surgical necrosectomy after initial • PCD • 3. Identification of factors that predicted the need for surgery in • patients initially treated with PCD

 • Secondary Endpoints • 1. Morbidity in patients managed with PCD • 2.

• Secondary Endpoints • 1. Morbidity in patients managed with PCD • 2. Length of intensive care unit (ICU) and hospital stay • 3. Number and size of catheters required • 4. Number of interventions required • 5. Catheter-related complications • 6. Morbidity and mortality in patients requiring necrosectomy.

 • TABLE 1. Definitions Used to Diagnose Organ Failure, Endpoints, and Factors •

• TABLE 1. Definitions Used to Diagnose Organ Failure, Endpoints, and Factors • Organ Failure: Organ failure persisting for more than 48 hours of ICU stay and after appropriate medical management. Individual organ failure was defined by • the following measures: • Renal Failure: Creatinine level greater than 177 μmol/L (2 mg/d. L) after rehydration 1 • Circulatory Failure: Systolic blood pressure less than 90 mm Hg despite adequate fluid resuscitation 1 • Respiratory Failure: Pa. O 2 60 mm Hg or less despite Fi. O 2 of 0. 30, or need for mechanical ventilation 1 • Neurological Failure: GCS score ≤ 10 • MOF: When two or more organs failed • Gastrointestinal Bleeding: More than 500 milliliters of blood loss in 24 hours 1 • Hypocalcemia: Calcium level < 1. 87 mmol/L • Enterocutaneous Fistula: Discharge of either small- or large-bowel contents from a drain or a drain site or from the surgical wound • Parenteral Nutrition (PN) Requirement: Need to meet calorie requirement by PN in the presence of intolerance to either oral or nasoenteral tube feeds or lack • of access to gastrointestinal tract by way of naso-jejunal tube or because daily calorie requirement is not being met by the enteral route alone • Maximum Extent of Pancreatic Necrosis: Maximum amount of necrosis of the pancreas observed on serial CT scans during the course of illness • Infected Pancreatic Necrosis: Positive culture obtained either from needle aspiration or specimen obtained from PCD preoperatively. Patients showing air foci • (emphysematous changes) in imaging studies of the pancreatic bed before radiological intervention were also labeled as having infected pancreatic necrosis • Sterile Necrosis: Negative culture obtained either from needle aspiration or specimen from PCD. Patients who did not undergo sampling because of their • benign course were also considered to have sterile necrosis • Polymicrobial Status: Positive culture of two or more organisms obtained from a specimen of single PCD or specimen obtained at the same time from different • PCDs or serial specimens obtained from single or different PCDs in a patient with ongoing sepsis • Sepsis: Positive blood culture/aspirate and more than one of the following clinical signs 32: ie, rectal temperature < 36◦C or > 38◦C, tachycardia > 90/min, • tachypnea (respiratory rate > 20/min) or hyperventilation (pa. CO 2 < 4. 3 k. Pa), white blood cell count < 4 × 109/L or > 12 × 109/L, or the presence of more • than 10% immature neutrophils • Sepsis Reversal With PCD: Defined as defervescence, reversal of leukocytosis and sepsis-related organ failure with or without resolution of necrotic cavity • Efficacy of PCD in SAP: When PCD alone achieves sepsis control as well as resolution of the necrotic cavity by PCD, and operative debridement is avoided • Pancreatic Fistula: In patients whose drain outputs (either PCD or intraoperatively placed lesser-sac tube drains) prolonged for more than 3 months and drain • fluid amylase levels more than three times the serum amylase levels • Inadequate Drainage of Collection and Necrosis: Incomplete resolution of the necrotic cavity despite upsizing/placement of additional catheters and saline • irrigation • Failure to Thrive: Sepsis reversal with nonresolution of the necrotic cavity by PCD and associated with diminished appetite and inadequate oral/enteral intake, • failure to gain weight, and persistent hypoalbuminemia • Ongoing Sepsis: Simmering infection in which the patient has intermittent low-grade fever, with waxing and waning leukocyte count and imaging showing • incomplete resolution of the necrotic cavity, which may be accompanied by purulent discharge from the drains

 • PROPATRIA trial in Lancet(2008) Probiotics are not useful in predicted severe pancreatitis.

• PROPATRIA trial in Lancet(2008) Probiotics are not useful in predicted severe pancreatitis. • PANTER trial in NEJM(2010) Minimally invasive step-up approach reduces major Cx and mortality in infected necrotizing pancreatitis, compared with primary open necrosectomy. • PENGUIN trial in JAMA(2012) In patients with infected necrotizing pancreatitis, an endoscopic necrosectomy reduces the pro-inflammatory response of the body, compared to a surgical necrosectomy. • PYTHON trial in NEJM(2014) In patients with predicted severe pancreatitis, early enteral nutrition does not reduce the combined endpoint of major infections or death compared to nutrition on request. • PONCHO trial in Lancet(2015) In patients with mild biliary pancreatitis, an early cholecystectomy reduces the risk of recurrent gallstone symptoms compared with a late cholecystectomy. • TENSION trial in Lancet(2017) In patients with infected necrotizing pancreatitis, the endoscopic step-up approach is not superior to the surgical step-up approach in reducing serious complications or mortality. The incidence of pancreatic fistula and the duration of hospital stay were lower in the endoscopic arm.

 • American College of Gastroenterology (ACG) • At adm • Patient -Age(>55) -Obesity(BMI

• American College of Gastroenterology (ACG) • At adm • Patient -Age(>55) -Obesity(BMI >30) -Altered mental status • SIRS • >2 of the following criteria: PR(>90) -RR(>20) or Pa. CO 2(>32) • Labs • -BUN(>20 mg/dl) at adm • Radiology • -Pleural effusions -Rising BUN -Pulmonary infiltrates –BT(>38) -HCT(>44%) -Comorbid disease -WBC(>12, 000) -Rising HCT -Elevated Cr -Multiple or extensive extrapancreatic collections • The presence of organ failure and/or pancreatic necrosis defines severe acute pancreatitis

Severity of acute pancreatitis SOCIETY GUIDELINES • International Association of Pancreatology (IAP)/ American Pancreatic

Severity of acute pancreatitis SOCIETY GUIDELINES • International Association of Pancreatology (IAP)/ American Pancreatic Association (APA) • SIRS at adm • During adm host risk factors (age, comorbidity, BMI), clinical risk stratification (persistent SIRS), response to initial therapy (persistent SIRS, BUN, Cr)

Timing of debridement (necrosectomy) • Early debridement: not helpful • Late debridement: preferred, 2

Timing of debridement (necrosectomy) • Early debridement: not helpful • Late debridement: preferred, 2 to 4 weeks later