Wong Po Yan, SabrinaWong Po Yan, Sabrina

Princess Margaret HospitalPrincess Margaret Hospital

Necrotizing pancreatitisNecrotizing pancreatitis

30% mortality

Necrotizing Pancreatitis20%

Infected Necrosis40 – 70%

Management StrategiesManagement Strategies

DiagnosisPrognosisOrgan support

+/- ERCP

Surgical intervention:• Abdominal compartment syndrome• Bleeding• Perforation of hollow viscus• Ischemic bowel

DiagnosisPrognosisOrgan support

+/- ERCP

Surgical intervention:• Abdominal compartment syndrome• Bleeding• Perforation of hollow viscus• Ischemic bowel

How can we predict severity?How can we predict severity?

Prognosis – Prognosis – Clinical & BiochemicalClinical & Biochemical

• Scoring systems– Ranson, Modified Glascow, APACHE II

• Persistent organ failure– SIRS, MODS, Modified Marshall, SOFA

• Single serum markers– BUN, CRP, hematocrit, procalcitonin

• Patient’s risk factors– Age, co-morbidities, ASA class, obesity

Guido Alsfasser et al. Scoring for human acute pancreatitis: state of the art. Langenbecks Arch Surg 2013; 398:789–797

Prognosis – Prognosis – RadiologicalRadiological

No mortality

17% mortality

Emil J. Balthazar. Acute pancreatitis: assessment of severity with clinical and CT evaluation. Radiology. 2002

If we know infection is our If we know infection is our next threat, can we prevent it?next threat, can we prevent it?

Prophylactic AntibioticsProphylactic Antibiotics• Choice of antibiotic:

(1) Spectrum of pathogens

Prophylactic AntibioticsProphylactic Antibiotics

Büchler M, Malfertheiner P et al. Human pancreatic tissue concentration of bactericidal antibiotics. Gastroenterology 1992;103:1902–1908.Gerard P Burn. Blood pancreatic juice barrier to antibiotic excretion. Am J Surg. 1986 ;151(2):205-8

• Choice of antibiotic: (1) Spectrum of pathogens(2) Penetration to pancreas

Prophylactic AntibioticsProphylactic Antibiotics

Mortality Infected pancreatic necrosis Non-pancreatic infection Operative treatment

Similar rate of fungal infection

Prophylactic AntibioticsProphylactic Antibiotics

Prophylactic AntibioticsProphylactic Antibiotics

MortalityMortality

Infected necrosisInfected necrosis

Prophylactic AntibioticsProphylactic Antibiotics

American College of Gastroenterology 2013 International Association of Pancreatology 2013 Japanese Society of HBP Surgery 2010 UK Working Party for Acute Pancreatitis 2005 ?

Management StrategiesManagement Strategies

Sterile necrosis: observe

Infected necrosis:DelayDrain

Debride

Sterile necrosis: observe

Infected necrosis:DelayDrain

Debride

How can we diagnose How can we diagnose infected necrosis?infected necrosis?

Diagnosis – Infected NecrosisDiagnosis – Infected Necrosis

Lack of enhancement Acute post-necrotic collection Walled off necrosis

Atif Zaheer et al. The revised Atlanta classification for acute pancreatitis: updates in imaging terminology and guidelines. Abdom Imaging 2013; 38:125–136

Diagnosis – Infected NecrosisDiagnosis – Infected Necrosis

Y Sheu et al. The revised Atlanta classification for acute pancreatitis: a CT imaging guide for radiologist. Emerg Radiol 2012; 19: 237 – 243.Beger HG, Bittner R, Block S, et al. Bacterial contamination of pancreatic necrosis. A prospective clinical study. Gastroenterology 1986;91:433–8.

Diagnosis – Infected NecrosisDiagnosis – Infected Necrosis

Clinical (n = 92)Clinical (n = 92) CT (n = 88)CT (n = 88) FNA (n = 28)FNA (n = 28)

80% 94% 86%

Mark C van Baal et al. The role of routine fine-needle aspiration in the diagnosis of infected necrotizing pancreatitis. Surgery 2014;155:442-8.

What should we choose?What should we choose?

Treatment – Infected NecrosisTreatment – Infected Necrosis

Modalities• Percutaneous• Retroperitoneal• Endoscopic• Laparoscopic• Open

D.W. da Costa et al. Staged multidisciplinary step-up management for necrotizing pancreatiti. BJS 2014; 101:e65 – e79sH.G. Gooszen et al. Surgical treatment of acute pancreatitis. Langenbecks Arch Surg 2013; 398: 799 – 806.

Modalities• Percutaneous• Retroperitoneal• Endoscopic• Laparoscopic• Open

VARDVARD

D.W. da Costa et al. Staged multidisciplinary step-up management for necrotizing pancreatitis. BJS 2014; 101:e65 – e79sH.G. Gooszen et al. Surgical treatment of acute pancreatitis. Langenbecks Arch Surg 2013; 398: 799 – 806.

Treatment – Infected NecrosisTreatment – Infected Necrosis

Modalities• Percutaneous• Retroperitoneal• Endoscopic• Laparoscopic• Open

D.W. da Costa et al. Staged multidisciplinary step-up management for necrotizing pancreatitis. BJS 2014; 101:e65 – e79s

Treatment – Infected NecrosisTreatment – Infected Necrosis

Modalities• Percutaneous• Retroperitoneal• Endoscopic• Laparoscopic• Open

D.W. da Costa et al. Staged multidisciplinary step-up management for necrotizing pancreatitis. BJS 2014; 101:e65 – e79s

Treatment – Infected NecrosisTreatment – Infected Necrosis

Modalities• Percutaneous• Retroperitoneal• Endoscopic• Laparoscopic• Open

D.W. da Costa et al. Staged multidisciplinary step-up management for necrotizing pancreatitis. BJS 2014; 101:e65 – e79s

Treatment – Infected NecrosisTreatment – Infected Necrosis

Modalities• Percutaneous• Retroperitoneal• Endoscopic• Laparoscopic• Open

K. Vasiliadis et al. The role of open necrosectomy in the current management of acute necrotizing pancreatitis: a review article. Surgery. 2013.

Treatment – Infected NecrosisTreatment – Infected Necrosis

Retrospective studiesHeterogeneous techniquesSelection biasPublication bias

Retrospective studiesHeterogeneous techniquesSelection biasPublication bias

M.C. van Baal et al. Systematic review of percutaneous catheter drainage as primary treatment for necrotizing pancreatitis. BJS 2011; 98:18 – 27Bello et al. Minimally invasive treatment of pancreatic necrosis. World J of Gastroenterol. 2012; 18(46) 6829 – 6835.S. V. Brunschot et al. Endoscopic transluminal necrosectomy in necrotizing pancreatitis: a systematic review. Surg Endosc 2014; 28: 1425 – 1438.

Systematic Review

Treatment – Infected NecrosisTreatment – Infected Necrosis

R Y Babu et al. Predictors of surgery in patients with severe acute pancreatitis managed by the step-up approach. Ann Surg 2013; 257: 737 – 750.

Treatment – Infected NecrosisTreatment – Infected Necrosis

↓ Interleukin 6 levels

↓ Composite clinical end points

New-onset multiple organ failure

↓ Number of pancreatic fistula

Endoscopic Endoscopic (10)(10)- 2 VARD

Surgical (10)Surgical (10)- 6 VARD- 4 laparotomy

(PENGUIN Trial, OJ Bakker, JAMA 2012)

Treatment – Infected NecrosisTreatment – Infected Necrosis

(PANTER Trial, HC van Santvoort, NEJM 2010)

Open (45)Open (45)- 44 laparotomy- 1 VARD19 repeat15 drainage

Step-up (43)Step-up (43)- 41 percutaneous- 2 endoscopic19 2nd drainage24 VARD2 open

35% treated with percutaneous drainage only

↓ Composite end points

↓ New-onset multiple organ failure

↓ Incisional hernia

↓ New-onset diabetes

↓ Use of pancreatic enzymes

↓ Cost

Treatment – Infected NecrosisTreatment – Infected Necrosis

Percutaneous drainage

Endoscopic drainage

CTIf not possible Failed 72 hrs

Repeat drainage /drain adjustment

STEP 1

VARD Open

STEP 2

PANTER TrialPANTER Trial

Treatment – Infected NecrosisTreatment – Infected Necrosis

Treatment – Infected necrosisTreatment – Infected necrosis

Role of open necrosectomy

AL Madenci et al.Am J Surg 2014

Babu et al.Ann Surg 2010

• Outcome improved with modern intensive care

• Mortality rate 8.8%, 21%• Selection bias for patients

amendable to minimally invasive techniques

• Other indications for laparotomy

• PANTER trial: APACHE II score higher, mortality 16%

• Pre-op drainage in 18% & 71% indeed a step-up approach

• High risk of pancreatic fistula• Heterogeneous

C. F. Castillo. Open pancreatic necrosectomy: indications in the minimally invasive era. J Gastrointest. Surg 2011; 15: 1089 – 1091.

It’s not the end of the story…It’s not the end of the story…

DiabetesExocrine insufficiencyPancreatic fistulaDisconnected left pancreatic remnantVascular complications

DiabetesExocrine insufficiencyPancreatic fistulaDisconnected left pancreatic remnantVascular complications

SummarySummary

• A challenge

• Multi-disciplinary care

• Step-up approach for infected necrosis

Wong Po Yan, SabrinaWong Po Yan, Sabrina

Princess Margaret HospitalPrincess Margaret Hospital

Performance of scoring systemsPerformance of scoring systems

Ranson Sensitivity and PPV <80%

Modified Glascow Sensitivity and PPV <80%

APACHE II Varies with cut-off points and time of calculation>10 points at 24 hrs: sensitivity 71%, specificity 91%

SOFA >4 points at 48hr: sensitivity 86%, specificity 79%

Hematocrit < 44%: 90% NPV for severe pancreatitis

Blood urea nitrogen >7.14umol/l: odds ratio 4.6 for death

C-reactive protein >150 within 48hrs: 80% PPV for severe pancreatitis

SupplementarySupplementary

• 2005 – 2008• 7 university medical centers & 12 teaching hospitals• Randomization by block size of 4• Outcome assessors blinded• Baseline characteristics similar:

– APACHE score (14.6, 15.0)– CT severity index (median 8)– Time since onset of symptoms (30 days, 29 days)– % of infected necrosis (39%, 42%)

SupplementarySupplementary

SupplementarySupplementary

• Rationale of drainage:– Drain the infected fluid– Reduce the surgical trauma induced by open necrosectomy– Organ preservation

• Mortality similar:

Step up Open

Multi-organ failure 7 6

Bleeding 1 0

Pneumonia 0 1

SupplementarySupplementary

• 2006 – 2009, Massachusetts General Hospital• 68 patients

SupplementarySupplementary

SupplementarySupplementary

• 2000 – 2008 • 28 patients (1.8% of all acute pancreatitis)• 71% had prior percutaneous drainage• Indications of surgery:

– Unsuccessful percutaneous / endoscopic drainage (6)

– Suspected ischemic bowel (4), SB obstruction (1), hemorrhage from splenic artery pseudo-aneurysm (1), abdominal compartment syndrome (1)

• Closed lavage• After 1st operation:

– 43% required 2nd operation

– 54% required further percutaneous drainage

Acute necrotic collections & WONAcute necrotic collections & WON

(BJS 2014)

Independent factor for persistence:size > 6cm at baseline

74% at 6 months

Biliary drainageBiliary drainage

• Routine ERCP within 72 hrs:– No significant influence on mortality and

complications regardless of predicted severity

• Indications of early ERCP:– Cholangitis– Biliary obstruction

• Role of EUS:– Superior to MRCP to detect small (<5mm) stones– Prevent unnecessary ERCP

PathophysiologyPathophysiology

PathophysiologyPathophysiology

POPFPOPF

External pancreatic fistulaExternal pancreatic fistula

• Spontaneous closure 70 – 90%• Use of Octreotide:

– No consensus– Stop using it if no decrease in output– Side effect of gallstones

• Endoscopic transpapillary stenting– For side fistula

• Surgery

Disconnected left pancreatic remnantDisconnected left pancreatic remnant

• Can develop in up to 50% of patients with necrotizing pancreatitis– Neck and proximal body vulnerable to ischemia

• Endoscopic drainage: 25 – 50% failure rate• Operations:

– Distal pancreatectomy• Remnant <6cm, splenic vein thrombosis, poor

pancreatic duct quality

– Internal drainage• Pancreatico-jejunostomy / cystojejunostomy / fistulo-

jejunostomy

Murage KP, Ball CG, Zyromski NJ, et al. Clinical framework to guide operative decision making in disconnected left pancreatic remnant (DLPR) following acute or chronic pancreatitis. Surgery 2010;148:847–56

Disconnected left pancreatic remnantDisconnected left pancreatic remnant

Murage KP, Ball CG, Zyromski NJ, et al. Clinical framework to guide operative decision making in disconnected left pancreatic remnant (DLPR) following acute or chronic pancreatitis. Surgery 2010;148:847–56

Splenic vein thrombosisSplenic vein thrombosis

• 7 – 13%• Sinistral portal hypertension

isolated gastric varices• Risk of bleeding of gastric varices: 5 – 18%• Embolization: risk of splenic abscess• Splenectomy:

– Variceal bleeding– At time of distal pancreatectomy