Management of Acute Necrotizing Pancreatitis Dr Joyce WT Ng Tseung Kwan O Hospital

Prophylactic antibiotics Prophylactic antibiotics ERCP ERCP Nutritional support Nutritional support Inhibition of pancreatic secretion Inhibition of pancreatic secretion Surgical intervention Surgical intervention Indication Indication Timing Timing Modalities Modalities

Introduction Severe pancreatitis Severe pancreatitis Acute pancreatitis associated with the presence of organ failure or pancreatic/peri-pancreatic complications, or both Acute pancreatitis associated with the presence of organ failure or pancreatic/peri-pancreatic complications, or both Pancreatic necrosis Pancreatic necrosis Diffuse or focal areas of non-viable pancreatic parenchyma, typically associated with peri- pancreatic fat necrosis Diffuse or focal areas of non-viable pancreatic parenchyma, typically associated with peri- pancreatic fat necrosis A clinically based classification system for acute pancreatitis. Summary of the International Symposium on Acute Pancreatitis, Atlanta, Bradley EL et al. Arch Surg 1993

Surgical Intervention - Indications - Timing - Modalities

Indications: Infected Necrosis Infected pancreatic necrosis is a uniformly accepted indication for surgical intervention Infected pancreatic necrosis is a uniformly accepted indication for surgical intervention Acute Pancreatitis: Who Needs an Operation? Beger HG et la. J Hepatobiliary Pancreat Surg 2002 UK Guidelines for the Management of Acute Pancreatitis UK Working party on Acute Pancreatitis. Gut 2005 Acute Necrotizing Pancreatitis: Treatment Strategy According to the Status of Infection Buchler MW et la. Ann Surg 2000

Indications: Sterile Necrosis Over 90% of patients with sterile necrosis can be successfully treated without surgical intervention Over 90% of patients with sterile necrosis can be successfully treated without surgical intervention Acute Necrotiziing Pancreatitis: Treatment Strategy According to the Status of Infection. Treatment Strategy According to the Status of Infection. Buchler MW et la. Ann Surg 2000 Surgical treatment of sterile necrosis appears to have a higher mortality rates (11.9%, CI: ) than the conservative treatment (2.3%, CI: ) in patients with sterile necrosis Surgical treatment of sterile necrosis appears to have a higher mortality rates (11.9%, CI: ) than the conservative treatment (2.3%, CI: ) in patients with sterile necrosis Evidence-Based Treatment of Acute Pancreatitis. A look at Established Paradigms. Heinrich S et la. Ann Surg 2006

Indications: Sterile Necrosis Small group of sterile necrosis still warrants surgical interventions Small group of sterile necrosis still warrants surgical interventions Deteriorating condition despite maximal support Deteriorating condition despite maximal support Evidence-Based Treatment of Acute Pancreatitis. A look at Established Paradigms. Heinrich S et la. Ann Surg 2006 JPN Guidelines for the Management of Acute Pancreatitis: Surgical Management Isaji S et la. J Hepatobiliary Pancreat Surg, 2006

Surgical Intervention - Indications - Timing - Modalities

Timing First RCT First RCT Early ( 12 days, n=15) Early ( 12 days, n=15) Indication: MOF with clinical deterioration despite maximal intensive care Indication: MOF with clinical deterioration despite maximal intensive care Intervention: open packing with staged necrosectomy Intervention: open packing with staged necrosectomy Mortality: 56% (early) Vs 27% (Late) Mortality: 56% (early) Vs 27% (Late) Prematurely terminated because of very high mortality for early surgery group (odd ratio: 3.4) Prematurely terminated because of very high mortality for early surgery group (odd ratio: 3.4) Early versus Late Necrosectomy in Severe Necrotizing Pancreatitis. The American Journal of Surgery 1997 Feb;173(2):71-5. J Mier, E. Leon, A. Castillo, F Robledo, R Blanco

Timing. Timing of Surgical Intervention in Necrotizing Pancreatitis Besselink MG et al. Arch Surg 2007 Systemic review of 11 series Review of 1136 patients Only 1 RCT

Timing Not recommended early surgical intervention Not recommended early surgical intervention Late intervention Late intervention Separation of viable from non-viable tissue Separation of viable from non-viable tissue Reduced bleeding Reduced bleeding Removal of less normal pancreas Removal of less normal pancreas Operate on a more hemodynamically stable patient Operate on a more hemodynamically stable patient Analysis of the delayed approach to the management of infected pancreatic necrosis. Nilesh D et al. Word J Gastro 2011

Timing However, there was no consensus about the length of time that conservative treatment should be applied before surgical intervention should be considered However, there was no consensus about the length of time that conservative treatment should be applied before surgical intervention should be considered It is generalized accepted that at least 3-4 weeks of conservative management is desirable It is generalized accepted that at least 3-4 weeks of conservative management is desirable JPN Guideline for the Management of Acute Pancreatitis: surgical Management. Isaji S. et al. J Hepatobiliary Pancreat Surg 2006

Surgical Intervention - Indications - Timing - Modalities

Modalities Open necrosectomy Open necrosectomy Minimally invasive necrosectomy Minimally invasive necrosectomy Percutaneous Percutaneous Endoscopic Endoscopic Laparoscopic assisted Laparoscopic assisted

Open necrosectomy Classical modality over the past decades Classical modality over the past decades Principles: control septic foci Principles: control septic foci Debridement of the necrotic tissue Debridement of the necrotic tissue Post-operative lavage: removal of retroperitoneal debris and exudates Post-operative lavage: removal of retroperitoneal debris and exudates Mortality rate: 13-43% Mortality rate: 13-43% Surgery in the Treatment of Acute Pancreatitis – Open Pancreatic Necrosectomy. Werner J et la. Scand J Surg 2005

Open necrosectomy 4 principle techniques: 4 principle techniques: 1. Opening packing 2. Planned, staged relaparotomies with repeated lavage 3. Necrosectomy with continuous lavage of the lesser sac and retroperitoneum 4. Necrosectomy with closed packing

1. Open Packing Cavity lined with a non adherent dressing Cavity lined with a non adherent dressing Necrosectomy every 48 hours Necrosectomy every 48 hours Until no further necrosis is evident Until no further necrosis is evident

2. Planned, staged relaparotomies with repeated lavage Planned reoperation for repeated necrosectomies in 48 hour interval Planned reoperation for repeated necrosectomies in 48 hour interval Wound closed in delayed primary fashion Wound closed in delayed primary fashion

3. Necrosectomy with continuous lavage of lesser sac and relaparotomies 2 or more double-lumen drain for outflow 2 or more double-lumen drain for outflow Single-lumen drain for inflow Single-lumen drain for inflow Post operative continue lavage Post operative continue lavage Drains can be removed within next 2-3 weeks depending of the appearance of the effluent and clinical course Drains can be removed within next 2-3 weeks depending of the appearance of the effluent and clinical course

4. Necrosectomy with closed packing The residual cavity was filled with multiple, large, gauzed filled Penrose drains The residual cavity was filled with multiple, large, gauzed filled Penrose drains Drains removed after a minimum of 7 days Drains removed after a minimum of 7 days

Open necrosectomy Single necrosectomy with post- operative lavage without planned relaparotomies seems to be less harmful Single necrosectomy with post- operative lavage without planned relaparotomies seems to be less harmful More complications (e.g. fistula, incisional hernia, local bleeding) were seen in repeated laparotomies More complications (e.g. fistula, incisional hernia, local bleeding) were seen in repeated laparotomies Surgery in the Treatment of Acute Pancreatitis – Open Pancreatic Necrosectomy. Werner J et la. Scand J Surg 2005 Acute Pancreatitis at the beginning of the 21 st century: The state of the art. Tonsi AF et al. World J Gastroenterol 2009

Minimally Invasive Necrosectomy Developed in recent 2 decades Developed in recent 2 decades It is generally accepted to have comparable results with open necrosectomy It is generally accepted to have comparable results with open necrosectomy No randomized studies for comparison No randomized studies for comparison Approaches: Approaches: Percutanoeus Percutanoeus Endoscopic Endoscopic Laparoscopic-assisted Laparoscopic-assisted

1. Percutaneous Necrosectomy An endoscope is inserted into the retroperitoneal space under GA An endoscope is inserted into the retroperitoneal space under GA Utilize CT guided placement of small calibre percutanous drain into retroperitoneum Utilize CT guided placement of small calibre percutanous drain into retroperitoneum Mainly over left flank Mainly over left flank The tract is then dilated for passage of the scope The tract is then dilated for passage of the scope Remove debris by lavage and piecemeal extraction of necrotic debris Remove debris by lavage and piecemeal extraction of necrotic debris Post operative continuous lavage Post operative continuous lavage NICE Guideline for Percutaneous Pancreatic Necrosectomy

1. Percutaneous Necrosectomy Studyn Delay to necrosectomy, days, median (range) Pre-op infected necrosis Technique Post- op irrigati on Procedures per patient, n Major complication s, % Laparotomy required, n Intensive care unit stay, days Inpatient stay, days Mortality Shelat & Diddapur Seldinger + nephroscope Gambiez et al (mean)13 Lumbotomy + mediastinoscope 205 ± 4 (mean)22N/A 62 ± 21 (mean) 2 Chang et al (average) (14–56)13 Left flank incision + Blunt dissection 0N/A31 39 (average) (7–95) 23.2 (average) (4–120) 3 Besselink et al (0–181)7 Left-sided lumbotomy + VARD 02 (1–11)6N/A2 (0–83)100 (43–240)2 (11) Mui et al N/A9 Seldinger + choledochoscop e 03 (2–8)220 (0–64)84 (29–163)1 Connor et al (3–161)38N/A 3 (1–9)43120 (0–66)64 (15–272)9 Castellanos et al (average) (1–28)11 Left translumbar + flex endoscope 15 (mean) 3–10N/A033 (3–85)98 (34–210)3 Risse et al (mean) (28–92)6 Seldinger + nephroscope 02 (1–4) Carter et al (13–187)10 Nephrostomy + nephroscope + STE 103 (1–6)11442 (23–213)2 Current Status of Minimally Invasive Necrosectomy for Post-inflammatory Pancreatic Necrosis. Babu BI et al. HPB 2009

1. Percutaneous Necrosectomy Potential advantages: Potential advantages: Less postoperative physiological disturbance Less postoperative physiological disturbance Reduced need for intensive care Reduced need for intensive care Fewer complications Fewer complications Limitations: Limitations: May not have feasible route for necrosis in head or uncinate region May not have feasible route for necrosis in head or uncinate region May require multiple sessions (subsequent session can be done under LA) May require multiple sessions (subsequent session can be done under LA) Minimal Access Retroperitoneal Pancreatic Necrosectomy Improvement in Morbidity and Mortality With a Less Invasive Approach. Raraty MGT et la. Ann Surg 2010

2. Endoscopic Necrosectomy Usually under LA with sedation Usually under LA with sedation Localize the collection with EUS Localize the collection with EUS Transgastric/ transduodenal puncture Transgastric/ transduodenal puncture Tract is dilated and scope enter cavity Tract is dilated and scope enter cavity Necrosectomy under direct vision with irrigation, use of forceps or snares Necrosectomy under direct vision with irrigation, use of forceps or snares Placement of multiple nasocystic Placement of multiple nasocystic drains for post-operative drainage Peroral Transgastric/ Transduodneal Necrosectomy. Success in the Treatment of Infected Pancreatic Necrosis. Escourrou J et al. Ann Surg 2008

2. Endoscopic Necrosectomy Studyn Delay to necrosectomy, days, median (range) Pre-op infected necrosis Technique Post-op irrigation Procedures per patient, n Major complication s, % Laparotomy required Intensiv e care unit stay, days Inpatient stay, days Mortality Voermans et al (21–385)N/A EUS + endoscopic cyst entry 2520N/A5 (1–45)0 Papachristou et al (20–300)N/A Duodenoscope-19 + posterior transgastric-32 (60%) 533 (1–12)1112N/A13 (0–90)3 Will et al N/A Guidewire + needleknife N/A 2 (average) 2–6 (range) 000N/A Hookey et al (mean) (10–45)N/ATranspapillary + EUS6 Nasocystic 1 (median) (IQR 1– 1) 22N/A18 (10–35)1 Charnley et al (3–180)11 EUS + Electrocautery gastrotomy 13 Naso- cavity 4 (1–10)N/A1 2 Raczynski et al N/A EUS puncture + balloon dilatation + pigtail stent 2400N/A 0 Seewald et al N/A EUS + duodenoscope + guide + dilator 57N/A-2N/A 0 Baron et al N/A b 2 (1–6)16N/A 20 (0–75)1 Seifert et al N/A0EUS + needleknifeN/A 00 0 Current Status of Minimally Invasive Necrosectomy for Post-inflammatory Pancreatic Necrosis. Babu BI et al. HPB 2009

2. Endoscopic Necrosectomy Potential advantages Potential advantages Comparable results with open necrosectomy Comparable results with open necrosectomy Less postoperative physiological disturbance Less postoperative physiological disturbance Reduced need for intensive care Reduced need for intensive care Providing diagnostic and therapeutic option for biliary pathologies at the same session Providing diagnostic and therapeutic option for biliary pathologies at the same session Limitations Limitations Highly skilled experienced interventional endoscopist Highly skilled experienced interventional endoscopist Transient aggravation of sepsis and hemorrhage Transient aggravation of sepsis and hemorrhage Cannot deal with extended necrosis to paracolic gutter Cannot deal with extended necrosis to paracolic gutter Limited ability to evacuate large cavities Limited ability to evacuate large cavities Multiple sessions were required Multiple sessions were required Peroral Endoscopic Drainage/ Debridement of Walled-off Pancreatic Necrosis. Papachristou GI. Ann Surg 2007

3. Laparoscopic-assisted Necrosectomy 2-5 ports 2-5 ports +/- hand ports +/- hand ports Mainly with infra colic approach Mainly with infra colic approach

3. Laparoscopic- assisted Necrosectomy Studyn Delay to necrosectom y, days, median (range) Pre-op infected necrosis Technique Post-op irrigation Procedures per patient, n Major complicatio ns, % Laparotom y required, n Intensive care unit stay, days Inpatient stay, days Mortality Bucher et al (13–59)8 Single-port 5-mm scope 81 (2)000 (0–4)N/A0 Parekh a1965 (22–154)N/A 3 ports and hand-assist N/A 1 median (1–3) 136 ± 216 ± 42 Ammori ports all lap Horvath et al (27–77)6 2 ports, retroperiton eal No pneumo 3N/A 2 0 Zhu et al –31–3N/A 3 ports pneumo 3N/A 1 Alverdy et al (18–21)1 2-ports Seldinger 5- mm scope 02 (1–3)100N/A0 Current Status of Minimally Invasive Necrosectomy for Post-inflammatory Pancreatic Necrosis. Babu BI et al. HPB 2009

3. Laparoscopic- assisted Necrosectomy Potential advantages Potential advantages Decrease the trigger of systemic cytokine- mediated immune response Decrease the trigger of systemic cytokine- mediated immune response Better exposure Better exposure Possible complications Possible complications Spreading of infection to infracolic compartments Spreading of infection to infracolic compartments Similar morbidity rate compared with open surgery Similar morbidity rate compared with open surgery Laparoscopic-Assisted Pancreatic Necrosectomy. A new Surgical Option for Treatment of Severe Necrotizing Pancreatitis. Parekh D. Arch Surg 2006

First RCT First RCT Multi-centre (20 hospitals in Holland) Multi-centre (20 hospitals in Holland) Step-up Approach (45) Vs Open necrosectomy (43) Step-up Approach (45) Vs Open necrosectomy (43) Primary end-point: major complications/ death Primary end-point: major complications/ death A Step-up Approach or Open Necrosectomy for Necrotizing Pancreatitis (PANTER trial: Pancreatitis, Necrosectomy versus sTEp up appRoach) Santvoot HC et la. N Engl J Med 2010 Apr (16):

Major complication: 12% (step-up) Vs 40% (open), p= Major complication: 12% (step-up) Vs 40% (open), p= Mortality: 19% (step-up) Vs 16% (open), p= 0.7 Mortality: 19% (step-up) Vs 16% (open), p= 0.7 Primary end-point: 40% (step-up) Vs 69% (open), p= Primary end-point: 40% (step-up) Vs 69% (open), p= Conclusion: The minimally invasive step- up approach reduced the rate of the composite end point of major complications or death Conclusion: The minimally invasive step- up approach reduced the rate of the composite end point of major complications or death

Acute Pancreatitis Mild/ ModerateSevere Conservative treatment MOF Intensive Care Infected Necrosis Sterile Necrosis Intensive Care Failed 3-4weeks 1.Favourable condition 2.Available experts Surgery MIS approach Open necrosectomy