1. Management of Necrotizing Pancreatitis
Wong Po Yan, Sabrina
Princess Margaret Hospital

2. Necrotizing pancreatitis
20%
Infected Necrosis
40 – 70%
30% mortality

3. Management Strategies
Diagnosis
Prognosis
Organ support
+/- ERCP
Surgical intervention:
Abdominal compartment syndrome
Bleeding
Perforation of hollow viscus
Ischemic bowel
Acute pancreatitis runs a biphasic clinical course
The first phase lasting for 1-2 weeks is characterized by SIRS
Organ support including goal directed fluid resuscitation, nutrition
ERCP is suggested in patients with cholangitis and biliary obstruction
During the 1st week, emergency surgery is associated with high risk of mortality
Should be indicated only in cases with
Abdominal compartment syndrome failed conservative management and percutaneous catheter drainage
TNF- , IL-1 , IL-6, and IL-8, are released into the circulation  microcirculatory disorders
Most common organ failure = respiratory failure

4. How can we predict severity?

5. Prognosis – Clinical & 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
Scoring systems commonly used in clinical practice include the Ranson and modified Glascow scores, which only take into account patients’ condition within 48 hrs
APACHE II is complicated but it’s more flexible and provides a continuous assessment
Persistent organ failure beyond 1st weeks is associated with higher mortality
Organ failure can be quantified by many scoring systems
Because these scoring systems are not very user friendly, people also found single serum markers for prognosis
And we should not forget patient’s own risk factors
If we look at this whole list of parameters, we know that there’s no single test that is universally good.
Guido Alsfasser et al. Scoring for human acute pancreatitis: state of the art. Langenbecks Arch Surg 2013; 398:789–797

6. Prognosis – Radiological
No mortality
17% mortality
In necrotizing pancreatitis, CT scan is important for diagnosis and prognosis
Esp for local complications
Emil J. Balthazar. Acute pancreatitis: assessment of severity with clinical and CT evaluation. Radiology. 2002

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

8. Prophylactic Antibiotics
Choice of antibiotic: (1) Spectrum of pathogens
70% infection is mono-microbial
The most common bacteria is E coli, Gram-ve organisms
Followed by gram+ve organisms
Fungal infection is related to prolonged use of antibiotic therapy
Several hypothetical mechanisms by which bacteria may enter pancreatic and peripancreatic necrosis exist: the hematogenous route via circulation; transmural migration through the colonic bowel wall to the pancreas; via the lymphatic circulation; via the biliary duct system; and from the duodenum via the main pancreatic duct

9. Prophylactic Antibiotics
Choice of antibiotic: (1) Spectrum of pathogens (2) Penetration to pancreas
This factor includes the type and frequency of bacteria found in infected pancreatic necrosis, antibiotic tissue concentrations, and the percentage of inhibited bacterial strains according to the minimal inhibitory concentration (MIC).
Selective excretion of antibiotics into pancreatic juice and selective uptake into pancreatic tissue
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 ;151(2):205-8

10. Prophylactic Antibiotics
Mortality
Infected pancreatic necrosis
Non-pancreatic infection
Operative treatment
Similar rate of fungal infection
Within 7 days after onset of attack
Duration of antibiotics 10 – 21 days
7 RCTs, 404 patients
CT proven pancreatic necrosis
No antibiotic resistance, similar rate of fungal infection

11. Prophylactic Antibiotics

12. Prophylactic Antibiotics
Mortality
Within 72 hrs
Infected necrosis

13. Prophylactic Antibiotics
American College of Gastroenterology 
International Association of Pancreatology
Japanese Society of HBP Surgery 
UK Working Party for Acute Pancreatitis ?
This controversy can continue for another hour of discussion but I’d like to conclude with these guidelines
They do not recommend the use of prophylactic antibiotics

14. Management Strategies
Sterile necrosis: observe
Infected necrosis:
Delay
Drain
Debride
In the third and fourth week, we enter into the 2nd phase which is characterized by CARS
Apart from organ failure, another challenge appears.
1 randomized study, 2 retrospective studies and 1 prospective study showed clinical benefit from postponing debridement for approximately 4 weeks after admission
High circulating concentrations of the anti-inflammatory mediators such as TNF- receptors, IL-10, IL-11, and IL-1ra

15. How can we diagnose infected necrosis?

16. Diagnosis – Infected Necrosis
Acute post-necrotic collection
Walled off necrosis
3 – 5 days
2nd week
4th week
Lack of enhancement
Atif Zaheer et al. The revised Atlanta classification for acute pancreatitis: updates in imaging terminology and guidelines. Abdom Imaging 2013; 38:125–136

17. Diagnosis – Infected Necrosis
1st week 24%
2nd week 46%
3rd week 71%
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.

18. Diagnosis – Infected Necrosis
Clinical (n = 92)
CT (n = 88)
FNA (n = 28)
Post hoc analysis of 208 patients
Positive culture obtained by intervention was taken as reference
Clinical: clinical deterioration (no definite algorithm)
CT: gas bubbles
FNA: unclear clinical and radiological signs
FNA is not without risks:
Contamination
False negative 25%; False positive 15%
Risk of procedure
Routine FNA is not recommended because delay approach is suggested in infected necrosis and initiation of treatment is based on clinical condition rather than positive FNA results
One may argue that FNA culture results may guide antibiotic choice, but:
- 27% cultures do not match the final micro-organisms obtained by intervention
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.

19. What should we choose?

20. Treatment – 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 – e79s
H.G. Gooszen et al. Surgical treatment of acute pancreatitis. Langenbecks Arch Surg 2013; 398: 799 – 806.

21. Treatment – Infected Necrosis
Modalities
Percutaneous
Retroperitoneal
Endoscopic
Laparoscopic
Open
Sinus tract endoscopy (developed in Glascow)
A nephroscope inserted after dilatation of the tract to 30Fr
(2) VARD (developed in Seattle)
A percutaneous drain placed, then upsized every 3 – 4 days until 20 Fr drain placed which was eventually used as the VARD route
Subcostal incision
Put in 2 large bore drains for post-op lavage
81% requiring only 1 session
VARD
D.W. da Costa et al. Staged multidisciplinary step-up management for necrotizing pancreatitis. BJS 2014; 101:e65 – e79s
H.G. Gooszen et al. Surgical treatment of acute pancreatitis. Langenbecks Arch Surg 2013; 398: 799 – 806.

22. Treatment – Infected Necrosis
Modalities
Percutaneous
Retroperitoneal
Endoscopic
Laparoscopic
Open
Under sedation
+/- EUS guidance
The collection is punctured by 19 gauze needlde and guide-wire advanced under fluoroscopic guidance
Then the tract is ballooned dilated up to 8mm
2 or more pigtail stent inserted
Irrigation with 1L saline / 24 hrs through nasocystic catheter
Fatal air embolism has been reported in the multicentre Germany study
Therefore, carbon dioxide is more commonly used
D.W. da Costa et al. Staged multidisciplinary step-up management for necrotizing pancreatitis. BJS 2014; 101:e65 – e79s

23. Treatment – 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

24. Treatment – Infected Necrosis
Modalities
Percutaneous
Retroperitoneal
Endoscopic
Laparoscopic
Open
A few case series have been published on laparoscopic necrosectomy
Lesser sac is accessed through infra-colic approach or transgastric approach
Not widely used due to technical challenge
Risk of disseminating retroperitoneal infection into peritoneal cavity
D.W. da Costa et al. Staged multidisciplinary step-up management for necrotizing pancreatitis. BJS 2014; 101:e65 – e79s

25. Treatment – 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

26. Treatment – Infected Necrosis
Systematic Review
Median no.
Success
Mortality
Morbidity
Percutaneous (11)
2.5
55.7%
17.4%
21.2%
VARD (5) 1
88%
17%
46%
Endoscopic (14) 4
81% 6%
36%
Laparoscopic (2)
79%
10.3%
58%
Retrospective studies
Heterogeneous techniques
Selection bias
Publication bias
M.C. van Baal et al. Systematic review of percutaneous catheter drainage as primary treatment for necrotizing pancreatitis. BJS 2011; 98:18 – 27
Bello 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.

27. Treatment – Infected Necrosis
Successful Treatment
Case selection
Location of infected necrosis
Patient’s condition
Expertise
Predictors of Surgery
Renal failure
Higher APACHE II score at intervention
Number of bacteria isolated per patient
A prospective study in 2013 adopting the step-up approach compared patients with percutaneous drainage only and patients undergoing necrosectomy and found these predictors of surgery
(APACHE >7.5)
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.

28. Treatment – Infected Necrosis
(PENGUIN Trial, OJ Bakker, JAMA 2012)
Surgical (10)
6 VARD
4 laparotomy
Endoscopic (10)
- 2 VARD
↓ Interleukin 6 levels
↓ Composite clinical end points
 New-onset multiple organ failure
↓ Number of pancreatic fistula
Dutch pancreatitis study group
2008 – 2010
Radiologists and adjudication committee blinded for outcome assessment
Calculation of sample size is based on differences demonstrated in randomized trials of open vs. lap abdominal surgery
Randomization by computer generated block sequence
Adult patients requiring necrosectomy for suspected or confirmed infected necrotizing pancreatitis were included

29. Treatment – Infected Necrosis
(PANTER Trial, HC van Santvoort, NEJM 2010)
Open (45)
44 laparotomy
1 VARD
19 repeat
15 drainage
Step-up (43)
41 percutaneous
2 endoscopic
19 2nd drainage
24 VARD
2 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
19 patients required additional laparotomies because of ongoing sepsis or complications
Step up group:
2 patients had primary laparotomy because of no retroperitoneal access route
1 VARD converted to laparotomy
14 required additional necrosectomy
7 (of the 26 patients with necrosectomy) required percutaneous drainage afterwards

30. Treatment – Infected Necrosis
PANTER Trial
Percutaneous drainage
Endoscopic drainage CT
If not possible
Failed 72 hrs
Repeat drainage / drain adjustment
STEP 1
VARD
Open
STEP 2

31. Treatment – 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
Difficult to compare studies directly because of different patient population, entry criteria and surgical techniques
C. F. Castillo. Open pancreatic necrosectomy: indications in the minimally invasive era. J Gastrointest. Surg 2011; 15: 1089 – 1091.

32. It’s not the end of the story…
Diabetes
Exocrine insufficiency
Pancreatic fistula
Disconnected left pancreatic remnant
Vascular complications

33. Summary A challenge Multi-disciplinary care
Step-up approach for infected necrosis

34. Management of Necrotizing Pancreatitis
Wong Po Yan, Sabrina
Princess Margaret Hospital

35. Performance of scoring systems
Ranson
Sensitivity and PPV <80%
Modified Glascow
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
Acute physiologic and chronic health evaluation
Multiple organ dysfunction score
Sepsis-Related Organ Failure Assessment

36. Supplementary
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%)

37. Supplementary

38. Supplementary Rationale of drainage: Mortality similar:
Drain the infected fluid
Reduce the surgical trauma induced by open necrosectomy
Organ preservation
Mortality similar:
Not a study to demostrate difference in mortality
Sample size thousands to show clinically significant difference
Step up
Open
Multi-organ failure 7 6
Bleeding 1
Pneumonia

39. Supplementary 2006 – 2009, Massachusetts General Hospital 68 patients
Median days from onset = 39.5

40. Supplementary
Median days from onset = 39.5

41. Supplementary 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
Median time from onset = 34 days

42. Acute necrotic collections & WON
(BJS 2014)
Independent factor for persistence:
size > 6cm at baseline
Drainage:
Infected / symptomatic = 6
at time of cholecystectomy = 2
Persistent cyst after 32 weeks = 2
74% at 6 months

43. Biliary 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

44. Pathophysiology

45. Pathophysiology

46. POPF

47. External 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

48. Disconnected 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
Diagnosis:
- ERCP evidence of discontinuity of main pancreatic duct; cannot cannulate it
CT evidence of viable upstream pancreatic remnant
>2cm necrosis segment
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

49. Disconnected 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

50. Splenic 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