1. Infected necrotizing pancreatitis
보라매 소화기내과
정지봉

2. Clinical course of acute pancreatitis (AP)

3. Classification of AP

4. Necrotizing pancreatitis
Terminolgoy of AP (I)
Necrotizing pancreatitis
Lack of parenchymal enhancement by iv contrasts on CT
Acute necrotic collection (ANC), <4wks
- Heterogeneous and non-liquid density
No definable wall structure
Walled-off necrosis (WON), >4wks
- 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

5. Necrotizing pancreatitis
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), >4weeks
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

6. 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

8. 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.

9. Timing of debridement (necrosectomy)
Early debridement: not helpful
Late debridement: preferred, 3 to 4 weeks later

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

11. 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

12. - PCD followed by VARD vs. open pancreatic debridement
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

13. Endoscopic debridement
Limited to patients with WON in previous studies
Papachristou et al. Ann Surg 2007
Navaneethan et al. Pancreas 2009
Bradley EL 3rd 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 3rd et al. Ann Surg 2010

14. Endoscopic vs surgical step-up
da Costa, D. W. et al. Br. J. Surg, 2014

15. 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)

16. Which patients has the risk of additional necrosectomy after drainage?
Male, MOF, extent and heterogeneity of pancreatic necrosis
Hollemans et al. Ann Surg. 2016
MOF, Mean CT density of necrosis
This article
AUC=0.775
AUC=0.76

17. 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

19. 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.

20. Severity of acute pancreatitis
Scoring system

21. 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)

22. American College of Gastroenterology (ACG)
At adm
Patient
-Age(>55) -Obesity(BMI >30) -Altered mental status -Comorbid disease
• SIRS  
>2 of the following criteria:
PR(>90) RR(>20) or PaCO2(>32) –BT(>38) WBC(>12,000) 
Labs
-BUN(>20 mg/dl) at adm -Rising BUN -HCT(>44%) -Rising HCT -Elevated Cr
Radiology
-Pleural effusions -Pulmonary infiltrates -Multiple or extensive extrapancreatic collections
The presence of organ failure and/or pancreatic necrosis defines severe acute pancreatitis

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

25. 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 1wk of PCD, APACHE II score at the 1st PCD, and OF within 1wk after the onset of disease
Babu et al. Ann Surg. 2013
Mean CT density of necrosis, MOF, procalcitonin
This article

35. 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

36. 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)

37. 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

38. 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

39. 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.

40. 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/dL) after rehydration1
Circulatory Failure: Systolic blood pressure less than 90 mm Hg despite adequate fluid resuscitation1
Respiratory Failure: PaO2 60 mm Hg or less despite FiO2 of 0.30, or need for mechanical ventilation1
Neurological Failure: GCS score ≤ 10
MOF: When two or more organs failed
Gastrointestinal Bleeding: More than 500 milliliters of blood loss in 24 hours1
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 signs32: ie, rectal temperature < 36◦C or > 38◦C, tachycardia > 90/min,
tachypnea (respiratory rate > 20/min) or hyperventilation (paCO2 < 4.3 kPa), 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