Postponed or Immediate Drainage of Infected Necrotizing Pancreatitis

(POINTER): A Multicenter Randomized Trial.

Boxhoorn , S.M. van Dijk , J. van Grinsven ,H.C. van Santvoort, M.G. Besselink

July 01, 2023 Dutch Pancreatitis Study Group

M. ARUN
MODERTOR: DR MAHESH
• BACKGROUND:
• Infected necrosis complicates 10% of all acute pancreatitis episodes
and is associated with 15–20% mortality.
• The current standard treatment for infected necrotizing pancreatitis
is the step-up approach (catheter drainage, followed, if necessary, by
minimally invasive necrosectomy). (DUTCH PANTER TRIAL)
• Catheter drainage is preferably postponed until the stage of walled-
off necrosis, which usually takes 4 weeks.
• Whether outcomes could be improved by earlier catheter drainage is
unknown.
 • OBJECTIVE:
• The POINTER trial investigates whether immediate treatment with
catheter drainage is superior to the current practice of postponed
catheter drainage within the step-up approach in patients with
infected necrotizing pancreatitis.

• HYPOTHESIS
Proactive diagnosis of infected necrosis and immediate catheter
drainage prevents further clinical deterioration in these patients thus
reducing complications and possibly death, and reduces length of
hospital stay and costs as compared to postponed catheter drainage.
• METHODOLOGY:

• Multicentre,randomized superiority trial.

• Conducted at 22 centers in collaboration with the Dutch Pancreatitis

Study Group.
(From August 2015 to Oct 2019).
METHODOLOGY
• Patients were followed from the time of hospital admission by the trial
coordinators at the 22 participating centres.

• Patients in whom necrotizing pancreatitis developed were assessed for the

presence of infected pancreatitic necrosis.

• When infected necrosis was suspected or confirmed, the nationwide online

multidisciplinary expert panel of the Dutch Pancreatitis Study Group was
consulted to evaluate the eligibility of the patient for randomisation and the
indication for intervention.
DEFINITION OF INFECTED NECROSIS
First 14 days

• By a positive gram stain or culture from a fine needle aspiration.

• Presence of gas within pancreatic and peripancreatic necrosis on CECT.

After 14 days

• As persistent organ failure in patients admitted to the ICU or

• The persistent two inflammatory variables (temperature > 38.5 C oro
elevated CRP levels or leukocyte counts) during 3 consecutive days.
Inclusion Criteria:
• Documented infected necrotizing pancreatitis
• Suspected infected necrotizing pancreatitis, if > 14 days after onset
of disease
• Catheter drainage of the collection with infected necrosis is
technically feasible as deemed by the Expert panel and/or treating
physician
• Age ≥ 18 years
• Exclusion Criteria:
• > 35 days after onset of the acute pancreatitis

• Indication for emergency laparotomy for abdominal catastrophe (e.g.

bleeding, bowel perforation, abdominal compartment syndrome)

• Previous retroperitoneal intervention for necrotizing pancreatitis

• Documented chronic pancreatitis

• Immediate catheter drainage included treatment with antibiotics, catheter
drainage within 24 hours.

• Postponed catheter drainage included treatment with antibiotics and

postponing until the stage of walled-off necrosis, when necrotic
collections were largely or fully encapsulated

• Full encapsulation was not mandatory in patients whose condition was

deteriorating

• Image-guided percutaneous catheter drainage and endoscopic

transluminal drainage were both allowed as a first step.
• Insufficient clinical improvement within 72 hours, thin drains were
replaced with larger drains.

• If catheter drainage was clinically unsuccessful, minimally invasive

necrosectomy was performed (either videoscopic-assisted
retroperitoneal debridement or endoscopic transluminal
necrosectomy, depending on the route of initial drainage)

• Follow-up was completed 6 months after randomization.

• Outpatient follow-up visits, which included abdominal imaging and

evaluation of exocrine and endocrine pancreatic function, were
scheduled at 3 months and 6 months.
• Primary end point was score on the Comprehensive Complication Index calculated as the sum of
all complications graded according to the Clavien–Dindo classification overall score from 0 (no
complications) to 100 (death) for each patient

• Secondary end points: Death

Major complications
Bleeding resulting in intervention
Perforation of a visceral organ leading to intervention
Enterocutaneous fistula, pancreaticocutaneous fistula
New-onset organ failure [pulmonary, cardiovascular, renal]
Incisional hernia, wound infection
Endocrine and exocrine pancreatic insufficiency
Total number of surgical, endoscopic, and radiologic interventions
(catheter drainage necrosectomy)
• STATISTICAL ANALYSIS
• All analyses were based on the intention-to-treat principle. There
were no patients with missing data for the primary end point and few
with missing data for the secondary end points.

• A two-sided P value of less than 0.05 indicates statistical significance

for the primary end point.

• Statistical analyses were conducted with R software, version 3.6.1

(R Project for Statistical Computing).
RESULTS:

ENROLLMENT AND RANDOMIZATION

• 104 patients randomly assigned
• 55 to immediate drainage
• 49 to postponed drainage
• Baseline characteristics were similar
in the two groups.
• Baseline characteristics were similar
in the two groups.
Primary end point:

Mean Comprehensive
Complication Index score not
statistically different between
immediate drainage(57/100) and
postponed drainage (58/100)
groups.

(mean difference 1; 95%

confidence interval interval, -12 to
10 P=0.9)
Secondary end points:

• Mortality:13% in immediate and 10% in postponed-drainage group

(relative risk, 1.25; 95% CI, 0.42 to 3.68).
No significant differences were found in the incidence of major
complications, including new onset organ failure, bleeding, perforation
of visceral organ, enterocutaneous fistula, pancreatocutaneous fistula,
wound infection

• The mean number of interventions (catheter drainage and

necrosectomy) :4.4 vs 2.6 (mean difference, 1.8; 95% CI, 0.6 to 3.0).

• 19 patients (39%) in the postponed-drainage group, were treated

conservatively with antibiotics and did not require drainage; 17 of
these patients survived.
Need of Necrosectomy at 6 months:
RESULTS:
• This trial did not show the benefit of early intervention in
patients with infected necrotizing pancreatitis.

• With a postponed drainage strategy that included antibiotic

treatment, fewer interventions for infected necrosis were
performed and more than one third of patients were treated
conservatively.

• Future studies may focus on this treatment approach, including

ways to improve the appropriate use of antibiotic treatment.
DISCUSSION
• This multicenter, randomized trial did not show the superiority of
immediate catheter drainage over postponed catheter drainage in
reducing complications in patients with INP.

• Patients randomly assigned to the immediate-drainage group

underwent more interventions for infected necrosis, whereas the
postponed-drainage strategy averted the need for intervention in
more than one third of the patients assigned to that group.
• Results of this study do not support the hypothesis that catheter
drainage performed immediately after diagnosis of infected necrosis
leads to better patient outcomes with fewer complications than
postponed drainage.

• A recent retrospective study involving 193 patients with necrotizing

pancreatitis assessed outcomes after early treatment (76 patients
treated <4 weeks after disease onset) as compared with standard
treatment (117 patients treated ≥4 weeks after disease onset) with an
endoscopically centered step-up approach and showed similar
incidences of complications in the two groups.

• Patients in the early treatment group had longer hospital stays than
patients in the standard-treatment group, and a higher percentage of
patients in the early-treatment group died (13% vs. 4%, P=0.02)
• In this POINTER trial, the Comprehensive Complication Index
scores and mortality did not differ significantly between the groups.
• This trial did not show the hypothesized benefit of earlier catheter
drainage in patients with infected necrotizing pancreatitis.
• With a postponed drainage strategy that included antibiotic treatment,
fewer interventions for infected necrosis were performed and more
than one third of patients were treated conservatively.
• These findings suggest that an initial conservative approach with
antibiotics is justified when infected necrosis is diagnosed.
• Future studies may focus on this treatment approach, including ways
to improve the appropriate use of antibiotic treatment.
PROS:
• Multicentre
• Randomized controlled trial

CONS:
• Small sample size
• The Study protocol allowed for endoscopic and surgical approaches.
• Comprehensive Complication Index scores were intended for
assessment of postoperative complications. Not standard to compare
• Considerable number of patients were not eligible for randomization
due to late diagnosis of infected necrosis, previous intervention, or
because delaying intervention was not feasible.
• Encapsulation as a indicator for drainage was not an appropriate
marker for postponed drainage
Conclusions:
Endoscopic intervention of pancreatic necrosis in the third and fourth weeks
of illness appears effective and safe when a partial collection wall is present on
cross-sectional imaging studies, with outcomes paralleling those reported for
intervention of WON.
Nonoperative drainage in clinically stable patients is best delayed until
the development of walled-off necrosis, which usually occurs 30 or more
days after the onset of pancreatitis.
• No difference was seen in mortality.
• Mechanical intervention for NP was more common in the early than the late group
• (86% vs. 73%, p < 0.001)

Conclusion: Contemporary management of necrotizing pancreatitis is marked by less

frequent operative debridement and shorter disease duration.
WHAT IS THE NEED FOR LONGTERM
FOLLOW UP….?
• The question remains whether these relative benefits of the
postponed drainage approach persist after initial 6 month follow up.
• Some have argued that infected peri-pancreatic necrotic collections
that are initially treated conservatively with antibiotics could lead to
persistent complications requiring intervention& ultimately causing
mortality during longer follow up.
• Therefore, the current study evaluates new events beyond the initial
6 month follow up on long term clinical outcomes enrolled in the
POINTER trial.
OUTCOMES OF LONGTERM FOLLOW UP
• PRIMARY OUTCOMES:
• Death
• Major complications
New onset multiple organ failure
Bleeding requiring intervention
Perforation of visceral organ requiring intervention
Enterocutaneous fistula
OUTCOMES OF LONGTERM FOLLOW UP
• SECONDARY OUTCOMES
• Individual Major complications
• Incisional Hernia
• Pancreaticocutaneous fistula
• Wound Infection
• Interventions
• Total Length of intensive care
• Hospital stay related to pancreatitis length
• Recurrent acute pancreatitis& chronic pancreatitis
• Exocrine & endocrine pancreatic function
RESULTS OF LONGTERM FOLLOW UP

• PRIMARY OUTCOMES:
• The composite primary outcome of death & major complications occurred in 7/47
patients(15%) in the immediate drainage group and 7/41 patients(17%) in the postponed
group (p=0.78)
• Death occurred in 4 patients in the immediate drainage group(9%)& in 4 patients in the
postponed drainage group(10%)(p=1.0)
• 2 deaths in immediate drainage group were directly related to pancreatitis whereas none of the
deaths in the postponed drainage group.
PRIMARY OUTCOMES

IMMEDIATE
COMPLICATIONS POSTPONED GROUP p VALUE
GROUP

Death 9% 10% 1.0

PRIMARY OUTCOMES
• NEW ONSET ORGAN FAILURE:
• No significant differences were found in the individual components of major
complications

COMPLICATIONS IMMEDIATE GROUP POSTPONED GROUP P value

New onset organ

9% 5% 0.68
failure

Bleeding 2% 0% 1.0

Perforation of visceral
organ /
2% 2% 1.0
Enterocutaneous
fistula
SECONDARY OUTCOMES

COMPLICATIONS IMMEDIATE GROUP POSTPONED GROUP p VALUE

INCISIONAL HERNIA 4% 2% 0.54

PANCREATICOCUTANEO
US 2% 0% 1.0
FISTULA

WOUND INFECTION 2% 5% 0.6

RECURRENT ACUTE
15% 11% 0.47%
PANCREATITIS

CHRONIC PANCREATITIS 12% 5% 0.44%

NEED FOR INTERVENTION

INTERVENTIONS IMMEDIATE GROUP POSTPONED GROUP p VALUE

DRAINAGE PROCEDURES 15% 7% 0.33

NECROSECTOMIES 0% 0% 0.0

LENGTH OF HOSPITAL 0% 2% 0.09

STAY
DISCUSSION

• Long Term follow-up study of the POINTER trial confirms that a postponed
drainage approach for infected necrotizing pancreatitis resulted in fewer
interventions, as compared to immediate drainage , and almost a third of
these patients were successfully treated with antibiotics alone.

• Postponing or even omitting drainage does not lead to long- term adverse
outcomes with infected necrotizing pancreatitis.

• No benefits of immediate drainage in comparison with delaying intervention

were seen
DISCUSSION

• The most remarkable benefit of a postponed – drained approach found in the

initial POINTER trial was that 39% of patients assigned to the postponed-
drainage group were treated with antibiotics alone.( i.e no catheter drainage
or other intervention), with 35 % of patients surviving the trial’s initialm6
month follow up.

• In the current long term follow up study, this benefit occurred in 93% of the
surviving patients as intervention was required in one initially conservatively
treated patient.
DISCUSSION

• It should be pointed out here that the majority of patients did not suffer from
(multiple) organ failure at randomization.

• This is in line with previous studies that have reported similar success rate of
antibiotic treatment ( 3- 39%) in selected patients with infected necrotizing
pancreatitis, mostly in patients without organ failure.
WHAT IN CASES OF ORGAN FAILURE..?

• A recent PILOT randomized controlled Trial evaluated the optimal timing of

percutaneous drainage in necrotizing pancreatitis with persistent organ
failure as the primary indication, reported a beneficial trend for early
drainage.

• But long term outcomes of both approaches are only evaluated by one small
non randomized study, wherein no difference in regression and recurrence of
collections were observed.
 Conclusion
Delayed Intervention scores over Immediate drainage in all aspects in
management of Infected Necrottizing Pancreatitis Management
DELAYED INTERVENT

• LONG TERM RESULTS OF

IMMEDIATE AND DELAYED
Fewer Interventi
ons
INTERVETION IN INP

IMMEDIATE DRAINAGE
Decreased nee
d
procedures and for drainage
necrosectomy

39% of the pati

treated with42anti ents were
biotics alone

No differences
in death and
individual majo
r complications QOL was simila
r in both the
groups
POSTPONED DRAINAGE APPROACH
FOR PATIENTS WITH INFECTED
NECROTIZING PANCREATITIS
Ready For Prime Time !!

Thank You

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