coMpliAnce With evideNce-based cliniCal Guidelines in the managemenT of Acute biliaRy pancreAtitis
Conditions: Acute Pancreatitis, Acute Pancreatic Necrosis, Acute Pancreatitis Due to Gallstones, Acute Pancreatic Fluid Collection, Acute Pancreatitis With Infected Necrosis, Acute Pancreatitis Without Necrosis or Infection, Acute Pancreatitis Due to Common Bile Duct Calculus, Acute Pancreatitis Recurrent, Acute Pancreatitis Without Necrosis or Infection (Diagnosis), Covid19
Sponsor: University of Cagliari

coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 
Study Protocol V.2.2 February 16
  
th  , 2021.
co
  M
  pli
  A  nce with evide
  
N  ce-based clini
  
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guidelines in the managemen
  
T   of acute bilia
  
R  y 
pancre
  
A  titis (
  
MANCTRA-1
  
). 
ClinicalTrials.Gov ID Number: NCT04747990
16th February, 2021.
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coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 
Study Protocol V.2.2 February 16
  
th  , 2021.
Title: coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy 
pancreAtitis (MANCTRA-1). 
ClinicalTrials.Gov ID Number: NCT04747990
ENDORSED BY THE WORLD SOCIETY OF EMERGENCY SURGERY (WSES)
Italian Society of Endoscopic Surgery and new technologies (SICE)
American College of Surgeons (ACS) Italy Chapter
Association of Italian Surgeons in Europe (ACIE)
Italian Surgical Research Group (ItSurg)
“Mario Negri” Institute for Pharmacological Research, Milan, Italy.
TO JOIN THE MANCTRA-1 STUDY, REGISTER YOUR CENTER:
https://docs.google.com/forms/d/e/1FAIpQLSdzv1VhszFFDIKsIPfD4NKtwCKKcRMJU2jjN6cW
XvF_77QlvA/viewform?usp=sf_link
TO ACCESS THE ONLINE DATABASE-CRF FORM:
https://docs.google.com/forms/d/e/1FAIpQLSe_SnA3sWQeCG6yad-
pEoHeKu0izDav1amQ1r70gGF3Myynrg/viewform?usp=sf_link
Principal Investigator
Dr. Mauro Podda, M.D.
Department of Emergency Surgery, Azienda Ospedaliero-Universitaria di Cagliari, University Hospital 
Policlinico Duilio Casula, Cagliari, Italy.
mauropodda@ymail.com
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coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 
Background
Acute pancreatitis (AP) is an inflammatory disease of the pancreas, most commonly caused by 
gallstones or excessive alcohol use. It represents a management challenge and a significant healthcare 
burden. The incidence of AP ranges globally from 5 to 30 cases per 100.000 inhabitants/year, and there 
is evidence that the incidence has been rising in recent years. The overall case-fatality rate for AP is 
roughly 5%, and it is expectedly higher for more severe stages of the disease [1, 2]. In most cases 
(80%), the outcome of AP is rapidly favorable [3]. However, acute necrotizing pancreatitis (ANP) may 
develop in up to 20% of cases and is associated with significant rates of early organ failure (38%), 
needing some surgical/endoscopic intervention (38%), and death (15%) [4].
In the United States, AP is a leading cause of inpatient care among gastrointestinal conditions: more 
than 270.000 patients are hospitalized for AP annually, at an aggregate cost of over 2.5 billion dollars 
per year [5]. In Europe, the UK incidence of AP is estimated as 15-42 cases per 100.000/year and is 
rising by 2.7% each year [6].
Several scientific societies published their clinical practice guidelines making recommendations on the 
management of AP [7] (Table_1-4). These guidelines' main topics are the diagnosis, antibiotic 
treatment, management in the intensive care unit, surgical and operative management, and open 
abdomen management.
Audits about biliary AP have been performed in Italy, Germany, France, and England, with quite 
disappointing results [8-11]. Indeed, in these audits, the treatment of biliary AP differed substantially 
from the recommendations. For example, less than 15% of the responders stated that they strictly 
followed all recommendations included in the guidelines in Germany, and 25.8% of patients did not 
receive definitive treatment for biliary AP within one year in the UK [12].
A recent study from Singapore aiming to review the clinical management of patients with AP in an 
HPB referral center in the light of assessing the compliance to the 2013 International Association of 
Pancreatology (IAP)/American Pancreatic Association (APA) and the 2015 Japanese guidelines found 
that only 50% of patients received Ringer lactate for initial fluid resuscitation, 38.7% received 
antibiotics as prophylaxis, 21.4% of patients with severe AP had early enteral nutrition, and only 21.4% 
patients with biliary AP had index admission cholecystectomy despite the recommendations [13]. In 
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coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 
another recent study by a Canadian group, only 25% of patients with gallstones AP underwent a 
cholecystectomy on the same admission. Furthermore, only one-quarter of patients in whom an index 
admission cholecystectomy was not possible underwent ERCP with sphincterotomy, and only one-third 
of patients with gallstones AP and an imaging-confirmed obstructed common bile duct had an ERCP 
and sphincterotomy [14]. Slow implementation of the recommendation on early cholecystectomy has 
also been reported in a Danish survey seeking compliance with the recommendations of the national 
reference program for the treatment of patients with gallstone disease [15], and a similar lack of 
compliance with guidelines was found in Italy, mainly regarding indications for endoscopic and 
surgical management [16].
Conversely, a recent study from Sweden has shown that the recurrence rate and associated costs can be 
reduced by improved compliance to current AP guidelines. The authors found that 80% of patients with 
biliary AP underwent definitive treatment during their first attack (68% cholecystectomy, 17% ERCP 
and sphincterotomy, 15% both interventions) [17].
Moreover, significant overall differences between the practice of HPB specialists and non-specialists in 
gallstone AP have been reported, especially regarding severity assessment, indication and timing of 
requesting CT scan, nutritional support, and in common bile duct assessment before cholecystectomy 
[18].
These findings support the view that publication alone of nationally or internationally developed and 
approved guidelines is insufficient to modify the practice of non-specialists and raises the question of 
how best to spread guideline recommendations. Previous reports, including the one from France in 
2012, have shown that major changes in biliary AP patients management were noticed since the French 
guidelines publication. In particular, after the publication of the mentioned guidelines, lipase levels 
were measured for establishing AP diagnosis by 99% (vs. 83% pre-guidelines), and a CT scan was 
performed at 48h by 69% (vs. 29% pre-guidelines) to evaluate AP severity. Antibiotic prophylaxis and 
enteral nutrition were proposed by 20% (vs. 57% pre-guidelines) and 58% (vs. 25% pre-guidelines) for 
necrotizing AP [19].
Management of pancreatic necrosis
Infection of pancreatic necrosis is the predominant driver of sustained morbidity and late mortality in 
patients with severe AP. The subset of patients with ANP may face a complicated and prolonged 
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coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 
clinical course, with an associated mortality of up to 30% if an infection develops in the necrotic 
collection [20, 21]. Optimal management of patients with pancreatic necrosis requires a 
multidisciplinary approach, and specific guidelines for this specific subgroup of patients have been 
recently released (Table_5). Although antibiotic prophylaxis may prevent or reduce necrosis 
colonization, the results of RCTs evaluating this approach and meta-analyses do not support 
prophylaxis [22]. Consequently, internationally applicable recommendations are that intravenous 
antibiotic prophylaxis is not recommended to prevent infectious complications in AP. However, several 
global overviews assessing reports from across the world of the use of antibiotics in prophylaxis in AP 
have shown a spread diffusion of such behavior [23].
COVID-19 and management of AP
In 2020, the spread of the virus Covid-19 had represented a pandemic, which also profoundly impacted 
the surgical community [24, 25]. The constant increase in the number of patients requiring treatment 
has represented a massive challenge for many involved countries' healthcare systems and could be their 
breaking point. In an emergency situation, resources must be concentrated and used rationally to handle 
the pandemic and continue handling the pre-existing diseases. In this context, most surgical 
departments were forced to re-schedule their activity, giving priority to urgent/emergent surgical cases 
and non-deferrable oncological cases. There are many ways the outbreak of the Covid-19 pandemic 
could have influenced daily clinical practice for patients with biliary AP, leading to a failure to adhere 
to the recommendations coming from the guidelines, especially those regarding the early and definitive 
treatment with cholecystectomy or ERCP and sphincterotomy. First of all, the recommendation to 
postpone all non-urgent endoscopic procedures during the peak of the pandemic. Second, the 
recommendation to conservatively treat inflammatory conditions such as acute cholecystitis and acute 
appendicitis wherever possible.
The rationale for the study
Despite existing evidence-based practice guidelines for the management of biliary AP, in Europe, 
clinical compliance with recommendations is lacking. Studies in this field have identified significant 
discrepancies between evidence-based recommendations and daily clinical practice.
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coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 
It is believed by many that clinical guidelines would help to decrease inappropriate variation in 
practice, that they provide a rational basis for referral, and that they would help to reduce uncertainty in 
the management of some conditions. Clinical guidelines also provide a basis for continuing medical 
education and can improve control of healthcare costs. However, the value of national and/or 
international guidelines is very much dependent on a strategy for their implementation.
Although different guidelines for the management of biliary AP have been published, they have not 
been adequately investigated, and compliance has generally been unsatisfactory. Deficiencies and lack 
of standardization of the management of AP worldwide have been reported.
The most commonly reported gaps between clinical practice and AP guidelines include the indications 
for CT scan, need and timing of artificial nutritional support, indications for antibiotics, and 
surgical/endoscopic management of biliary AP.
The MANCTRA-1 can identify a number of areas for quality improvement that will require new 
implementation strategies. We aim to summarize the main areas of sub-optimal care due to the lack of 
compliance with current guidelines to provide the basis for introducing a number of bundles in AP 
patients' management to be implemented during the next years.
Aim of the study
Since the clinical compliance with recommendations about AP is poor and the impact of implementing 
guideline recommendations in biliary AP has not been well studied globally, we launched the 
MANCTRA-1 study intending to demonstrate areas where there is currently a sub-optimal 
implementation of current guidelines on biliary AP.
Moreover, we argue that during the Covid-19 pandemic, the tendency to disregard the guidelines 
recommendations has been more marked than usual, and we will try to find out if AP patients' care 
during the Covid-19 pandemic resulted in a higher rate of adverse outcomes compared to non-
pandemic times due to the lack in the compliance of the guidelines.
Primary objective

To evaluate which items of the current AP guidelines, if disregarded, correlate with 
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coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 
negative clinical outcomes according to the different clinical presentations of the 
disease
Secondary objectives

To assess the compliance of surgeons worldwide to the most up-to-date international guidelines 
on biliary AP

To evaluate the medical and surgical practice in the management of biliary AP during the non-
pandemic (2019) and pandemic Covid-19 periods (2020)

To investigate outcomes of patients with biliary AP treatment during the two study periods
Primary outcomes

30-day mortality: assessed by the number of AP patients with biliary etiology deceased during 
the non-pandemic period (2019) and the Covid-19 pandemic period (2020)

30-day morbidity: assessed by the number of AP patients with biliary etiology who experienced 
any type of AP-related complication within 30-days from the hospital admission during the 
non-pandemic period (2019) and the Covid-19 pandemic period (2020)
Secondary outcomes

Early definitive treatment rate in 2019 vs. 2020: defined as treatment in accordance with the 
current guidelines (cholecystectomy or ERCP with endoscopic sphincterotomy during the same 
hospital admission or within 2 weeks of discharge)

30-day hospital readmission rate in 2019 vs. 2020: defined as hospital readmission within 30-
days from discharge for recurrent biliary AP while awaiting interval cholecystectomy, or due to 
post-cholecystectomy complications

Predictive factors of morbidity and mortality in patients with biliary AP
The compliance of surgeons to the most up-to-date international guidelines on biliary AP will be 
assessed through the analysis of the following attitudes:

Use of scoring systems for the diagnosis and severity grading of biliary AP
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coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 

Use of lipase dosage (for the diagnosis) and CRP (for the severity grading) during the 
diagnostic workup

Use of Ultrasound scan, CT scan, MRCP, and endoscopic Ultrasound scan (EUS) in the correct 
way and timing

Use of early ERCP and sphincterotomy in case of cholangitis and/or choledocholithiasis

Use of percutaneous and/or endoscopic drainage in case of infected pseudocyst or necrosis

Timing of surgical necrosectomy

Timing of re-laparotomy in case of open abdomen strategies

Use of prophylactic antibiotics/antifungals

Use of somatostatin analogs

Use of early enteral feeding 

Use of early definitive treatment strategies, including cholecystectomy and/or ERCP and 
sphincterotomy
Study design
The MANCTRA-1 study (coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of 
acute biliaRy pancreAtitis) is an international multicenter, retrospective cohort study to assess the 
outcomes of patients admitted to hospital with a diagnosis of biliary AP and the compliance of 
surgeons worldwide to the most up-to-dated international guidelines on biliary AP. The study compares 
data collected in 2019 (pre-pandemic period) with those of 2020 (Covid-19 pandemic period). 
Study population 
All consecutive adult patients admitted to the participating surgical departments with a clinical and 
radiological diagnosis of biliary AP (with and without concomitant cholecystitis) between 01/01/2019 
and 31/12/2020. Patient data will be retrospectively analyzed and demographic characteristics, 
comorbidity status, clinical and radiological findings, treatment strategies, 30-day morbidity and 
mortality will be evaluated.
Inclusion criteria
Patients of both sexes, ≥ 16 years old, admitted to any of the participating surgical departments and/or 
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coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 
internal medicine or gastroenterology departments for biliary AP in 2019 and 2020. 
Exclusion criteria
Patients with AP of etiology other than gallstones; Pregnant patients.
Study periods
The pre-pandemic period runs from 01/01/2019 to 31/12/2019. The Covid-19 pandemic period runs 
from 01/01/2020 to 31/12/2020. Data will be entered in the database from 01/03/2021 to 31/08/2021. 
Data collection (see also the “Analyzed Data” - CRF - paragraph below) 
All epidemiological, clinical and surgical data will be collected on a CFR that will be completed by 
accessing to a protected data system. The link for accessing the completion of the CFR will be sent via 
email to only one contact person (Local Lead) of each participating center.
Sample size
Studies on biliary AP found a mortality rate of approximately 10%. Patients with biliary AP tend to 
have a higher mortality than patients with alcoholic pancreatitis. However, this rate has been falling 
over the last 2 decades as improvements in supportive care have been initiated. In patients with severe 
disease (organ failure), who account for about 20% of presentations, mortality is approximately 30%. 
This rate has not decreased in the past 10 years. 
We estimate that a minimum of 200 patients per group (2019 vs. 2020) would yield a power of 0.80 (1-
ß) to establish whether changes in clinical care for patients with biliary AP during the Covid-19 
pandemic has impacted on overall mortality using a one-sided significance ɑ level of 0.05 (5%) with 
power sample size calculator (sealedenvelope.com). 
Statistical analysis
The dichotomous variables will be expressed as numbers and percentages, while continuous variables 
will be expressed as mean and SD, or median and IQR (minimum and maximum values). Student’s t 
test or ANOVA will be used for comparisons of continuous variables between groups. Chi-squared test 
or Fisher’s exact test, as appropriate, will be used for analysis of categorical data. Multilogistic 
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coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 
regression models will be used to investigate clinical attitudes, physical, laboratory, and radiologic 
variables predictive of morbidity and mortality. A value of P < 0.05 will be considered statistically 
significant.
Ethical aspects
This is an international observational study, it will not attempt to change or modify the clinical practice 
of the participating physicians. The study will meet and conform to the standards outlined in the 
Declaration of Helsinki and Good Epidemiological Practices. Every clinical center attending the study 
is responsible for Ethics Committee approval depending on the local policy for observational and non-
interventional studies. All surgeons involved in the patients’ recruitment will be included in the 
research authorship. 
Publication policy
The Local Lead and two Collaborators from each center will be listed as Co-authors in the final 
publications. Data will be published as a pool from all participating surgical units. Data emerged from 
the MANCTRA-1 study will be published irrespective of findings. Results will be published on 
ClinicalTrials.Gov and each manuscript that is generated based on the registry will be disseminated to 
all participating centers before final publication.
Safety issues
None.
Data collection 
In each centre, the coordinator will collect and compile data in an online case report system. Data will 
be recorded contemporaneously on a dedicated, secure server that allows collaborators to enter and 
store data in a secure system. No patient identifiable data (name, date of birth, address, telephone 
number, etc.) will be recorded.
Informed consent
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coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 
Due to its retrospective design, this observational study will not attempt to change or modify the 
laboratory or clinical practices of the participating physicians. Consequently, informed consent will not 
be required. 
Data management
Every local investigator is responsible for entering data on an on line case report form for every patient 
included in the study. 
Funding
This research has not received any specific grant from funding agencies in the public, commercial, or 
not-for-profit sectors.
Financial and Insurance
Not applicable.
Analyzed Data – CRF -
Section 1 – General Informations

Country

Name and Surname of the Local Lead

Email address of the local lead

Name and Surname of the Local Collaborator

Email address of the Local Collaborator
Section 2 – Demographic Characteristics

Year of hospital admission for acute biliary pancreatitis (2019 Vs. 2020)

Patient age

Sex (Female Vs. Male)

Covid-19 status on admission (Negative/Positive/Untested)
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coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 

Previous episodes of biliary pancreatitis (Yes/No)

Admitting speciality (HPB surgery/General Surgery/Internal Medicine/Gastroenterology)
Section 3 – Comorbidity

Charlson's comorbidity index

Body Mass Index - BMI

Clinical history of diabetes (No diabetes/Diabetes with organ disfunction/Diabetes without 
organ disfunction)

Clinical history of chronic pulmonary disease other than Covid-19 pneumonia (Yes/No)

Clinical history of hypertension (Yes/No)

Clinical history of atrial fibrillation (Yes/No)

Clinical history of ischemic hearth disease (Yes/No)

Clinical history of chronic kidney disease (Yes-under medications/Yes-in permanent renal 
replacement therapy or in preparation for it/No)

Clinical history of diseases of the hematopoietic system (Yes/No)

Patient on immunosuppressive medications on hospital admission (Yes/No)
Section 4 – Clinical Scores

Glasgow Coma Scale (GCS)

qSOFA

WSES (World Society of Emergency Surgery) sepsis score

BISAP (Bedside Index of Severity in Acute Pancreatitis) score

ASA score (1-2-3-4-5)

Glasgow-Imrie score

Ranson's score

Apache II score

Revised Atlanta Classification (Mild acute pancreatitis/Moderately severe acute 
pancreatitis/Severe acute pancreatitis)

Organ failure during the hospital stay (None/Cardiovascular/Respiratory/Renal)
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coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 
Section 5 – Vital signs on admission

Temperature

Systolic blood pressure

Hearth rate

Respiratory rate

Blood oxygen saturation

ICU admission during the hospital stay (Yes/No)
Section 6 – Laboratory tests on admission

WBC

Neutrophils

Platelets

INR (International Normalized Ratio)

C-reactive protein

Aspartate aminotransferase – AST

Alanine aminotransferase – ALT

Total bilirubin

Conjugated bilirubin

Gamma-glutamil-transpeptidase – GGT

Serum amylase

Serum lipase

Lactate DeHydrogenase – LDH

Procalcitonin – PCT

Lactates
Section 7 – Diagnostic Imaging 

Initial diagnostic imaging (Ultrasound scan on admission/CT scan on admission/CT scan 
<24h/CT scan 24-48h/CT scan >48h)
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coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 

MRCP (MRCP on admission/MRCP <24h/MRCP >24h/No) 

Endoscopic ultrasound scan (Yes <24 hours/Yes >24 hours/No)

Re-evaluation with CT scan (None/<7 days/7-14 days/15-30 days/>30 days)
Section 8 – Physical examination on admission (Localized abdominal pain/Localized abdominal 
rigidity/Diffuse abdominal pain/Diffuse abdominal rigidity/No abdominal pain/No abdominal rigidity)
Section 9 – Concomitant findings on admission

Choledocholithiasis (Yes/Yes with common bile duct obstruction/No)

Cholangitis (Yes/No)

ERCP with sphincterotomy (Yes-within 24 hours/Yes within 24-48 hours/Yes within 48-72 
hours/No)
Section 10 – 30-day Morbidity

Gastric outlet obstruction (Yes/No)

Pseudocyst (Yes/No)

Infected necrosis (Yes/No)

Endoscopic drainage of pseudocyst/walled-off necrosis (Yes/No)

CT-guided fine needle aspiration in case of infected pseudocyst/walled-off necrosis (Yes/No)

Surgical necrosectomy (Yes-laparoscopic/Yes-open/No)

Timing of surgical necrosectomy (< 2 weeks from the onset of symptoms/2-4 weeks/>4 weeks)

Setting of surgical necrosectomy (Upfront/After failure of endoscopic necrosectomy/After 
failure of endoscopic and percutaneous necrosectomy)

Cystogastrostomy (Yes-endoscopic/Yes-surgical/No)

Abdominal compartment syndrome (Yes/No)

Open abdomen (Yes/No)

Timing of re-exploration (24-48 hours/48-72 hours/>72 hours)

Bleeding (Yes/No)

Bowel ischemia (Yes/No)
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coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 

Bowel fistula (Yes/No)

Necrotizing cholecystitis (Yes/No)
Section 11 – Medical Therapy

Antibiotic prophylaxis (Yes/No)

Antifungal prophylaxis (Yes/No)

Use of somatostatin analogs (Yes/No)

Nutritional support on admission (Oral/Enteral via nasogastric feeding tube/Enteral via 
nasojejunal feeding tube/Total parental nutrition/Nihil per os)
Section 12 – Cholecystectomy (Yes-within 3 days/Yes-within 7 days/Yes-within 14 days/No-delayed 
cholecystectomy)
Section 13 – 30-day Overall mortality (Yes/No)
Section 14 – Post-cholecystectomy 30-day morbidity and mortality

Post-cholecystectomy morbidity (Yes/No)

Post-cholecystectomy mortality (Yes/No)

30-day hospital readmission (No/Yes-due to surgical complications/Yes-due to recurrent 
pancreatitis while awaiting interval cholecystectomy)
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coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 
Table_1: Statements and Recommendations from the 2019 WSES guidelines for the management 
of Acute Pancreatitis patients.
1. Severity grading

Severe acute pancreatitis is associated with persistent organ failure 
(cardiovascular, respiratory, and/or renal), and high mortality. Both 
new classification systems, Revised Atlanta Classification and 
Determinant-based Classification of Acute Pancreatitis Severity, are 
similar in establishing the diagnosis and severity of acute pancreatitis 
(1C).

Patients who have persistent organ failure with infected necrosis have 
the highest risk of death (1C).

Patients with organ failures should be admitted to an intensive care 
unit whenever possible (1C).
2. Imaging 

On admission, ultrasound (US) should be performed to determine the 
etiology of acute pancreatitis (biliary) (1C).

When doubt exists, computed tomography (CT) provides good 
evidence of the presence or absence of pancreatitis (1C).

All patients with severe acute pancreatitis need to be assessed with 
contrast-enhanced computed tomography (CE-CT) or magnetic 
resonance imaging (MRI). Optimal timing for first the CE-CT 
assessment is 72–96 h after onset of symptoms (1C).

Magnetic resonance cholangiopancreatography (MRCP) or 
endoscopic ultrasound should be considered to screen for occult 
common bile duct stones in patients with unknown etiology (1C).
3. Diagnostic laboratory 
parameters

The cut-off value of serum amylase and lipase is normally defined to 
be three times the upper limit.

C-reactive Protein level ≥ 150 mg/l at third day can be used as a 
prognostic factor for severe acute pancreatitis (2A).

Hematocrit > 44% represents an independent risk factor of pancreatic 
necrosis (1B).

Urea > 20 mg/dl represents itself as an independent predictor of 
mortality (2B).

Procalcitonin is the most sensitive laboratory test for detection of 
pancreatic infection, and low serum values appear to be strong 
negative predictors of infected necrosis (2A).

In the absence of gallstones or significant history of alcohol use, 
serum triglyceride and calcium levels should be measured. Serum 
triglyceride levels over 11.3 mmol/l (1000 mg/dl) indicate it as the 
etiology (2C).
4. Diagnostics in 
idiopathic pancreatitis 

In idiopathic pancreatitis, biliary etiology should be ruled out with 
two ultrasound examinations, and if needed MRCP and/or 
endoscopic ultrasound EUS, to prevent recurrent pancreatitis (2B).
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coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 
5. Risk scores

There are no “gold standard” prognostic score for predicting severe 
acute pancreatitis. Probably the bedside index of severity of acute 
pancreatitis (BISAP) score is one of the most accurate and applicable 
in everyday clinical practice because of the simplicity and the 
capability to predict severity, death, and organ failure as well as the 
APACHE-II (very complex) and other scores (1B).
6. Follow-up imaging 

In severe acute pancreatitis (computed tomography severity index ≥ 
3), a follow-up CECT scan is indicated 7–10 days from the initial CT 
scan (1C).

Additional CE-CT scans are recommended only if clinical status 
deteriorates or fails to show continued improvement, or when 
invasive intervention is considered (1C).
7. Prophylactic 
antibiotics

Recent evidences have shown that prophylactic antibiotics in patients 
with acute pancreatitis are not associated with a significant decrease 
in mortality or morbidity. Thus, routine prophylactic antibiotics are 
no longer recommended for all patients with acute pancreatitis (1A).
8. Infected necrosis and 
antibiotics

Antibiotics are always recommended to treat infected severe acute 
pancreatitis. However the diagnosis is challenging due to the clinical 
picture that cannot be distinguished from other infectious 
complications or from the inflammatory status caused by acute 
pancreatitis (2A).

Serum measurements of procalcitonin (PCT) may be valuable in 
predicting the risk of developing infected pancreatic necrosis (1B).

A CT-guided fine-needle aspiration (FNA) for Gram stain and culture 
can confirm an infected severe acute pancreatitis and drive antibiotic 
therapy but is no longer in routine use (1B).
9. Type of antibiotics

In patients with infected necrosis, antibiotics known to penetrate 
pancreatic necrosis should be used (1B).

In patients with infected necrosis, the spectrum of empirical antibiotic 
regimen should include both aerobic and anaerobic Gram-negative 
and Gram-positive microorganisms. Routine prophylactic 
administration of antifungal is not recommended in patients with 
infected acute pancreatitis, although Candida spp. are common in 
patients with infected pancreatic necrosis and indicate patients with a 
higher risk of mortality (1B).
10. Monitoring

Continuous vital signs monitoring in high dependency care unit is 
needed if organ dysfunction occurs. Persistent organ dysfunction or 
organ failure occurrence despite adequate fluid resuscitation is an 
indication for ICU admission (1C).
11. Fluid resuscitation

Early fluid resuscitation is indicated to optimize tissue perfusion 
targets, without waiting for hemodynamic worsening. Fluid 
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administration should be guided by frequent reassessment of the 
hemodynamic status, since fluid overload is known to have 
detrimental effects. Isotonic crystalloids are the preferred fluid (1B).
12. Pain control 

No evidence or recommendation about any restriction in pain 
medication is available. Nonsteroidal anti-inflammatory drugs 
(NSAID) should be avoided in acute kidney injury (AKI). Epidural 
analgesia should be an alternative or an agonist with intravenous 
analgesia, in a multimodal approach. Patient-controlled analgesia 
(PCA) should be integrated with every described strategy. (1C) 
Dilaudid is preferred over morphine or fentanyl in the nonintubated 
patient.
13. Mechanical 
ventilation

Mechanical ventilation must be instituted if oxygen supply, even with 
high flow nasal oxygen, or continuous positive airway pressure 
became ineffective in correcting tachypnea and dyspnea. Both non-
invasive and invasive techniques can be used, but invasive ventilation 
is mandatory when bronchial secretions clearance start to be 
ineffective and/or the patient is tiring of predicted to tire. Lung-
protective strategies should be used when invasive ventilation is 
needed (1C).
14. Increased intra-
abdominal pressure

Limitation of sedation, fluids, and vasoactive drugs to achieve 
resuscitative goals at lower normal limits is suggested. Deep sedation 
and paralysis can be necessary to limit intra-abdominal hypertension 
if all other nonoperative treatments including percutaneous drainage 
of intraperitoneal fluid are insufficient, before performing surgical 
abdominal decompression (1B)
15. Pharmacological 
treatment

No specific pharmacological treatment except for organ support and 
nutrition should be given (1B).
16. Enteral nutrition 

Enteral nutrition is recommended to prevent gut failure and infectious 
complications. Total parenteral nutrition (TPN) should be avoided 
but partial parenteral nutrition integration should be considered to 
reach caloric and protein requirements if enteral route is not 
completely tolerated. Both gastric and jejunal feeding can be 
delivered safely (1A).
17. Indications for 
emergent ERCP

Routine ERCP with acute gallstone pancreatitis is not indicated 
(grade 1A).

ERCP in patients with acute gallstone pancreatitis and cholangitis is 
indicated (grade 1B).

ERCP in acute gallstone pancreatitis with common bile duct 
obstruction is indicated (grade 2B).

ERCP in patients with predicted severe acute gallstone pancreatitis 
without cholangitis or common bile duct obstruction cannot be 
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recommended at this time (grade 2B).
18. Indications for 
percutaneous/endoscopi
c drainage of pancreatic 
collections

Clinical deterioration with signs or strong suspicion of infected 
necrotizing pancreatitis is an indication to perform intervention 
(percutaneous/endoscopic drainage)
After 4 weeks after the onset of the disease:
– On-going organ failure without sign of infected
necrosis
– On-going gastric outlet, biliary, or intestinal
obstruction due to a large walled off necrotic
collection
– Disconnected duct syndrome
– Symptomatic or growing pseudocyst
After 8 weeks after the onset of the disease:
– On-going pain and/or discomfort
(grade 1C)
19. Indications for 
surgical intervention 

As a continuum in a step-up approach after percutaneous/endoscopic 
procedure with the same indications
– Abdominal compartment syndrome
– Acute on-going bleeding when endovascular approach is unsuccessful
– Bowel ischaemia or acute necrotizing cholecystitis during acute 
pancreatitis
– Bowel fistula extending into a peripancreatic collection
(Grade 1C)
20. Timing of surgery

Postponing surgical interventions for more than 4 weeks after the 
onset of the disease results in less mortality (2B).
21. Surgical strategy

In infected pancreatic necrosis, percutaneous drainage as the first line 
of treatment (step-up approach) delays the surgical treatment to a 
more favorable time or even results in complete resolution of 
infection in 25–60% of patients and it is recommended as the first 
line of treatment (1A).

Minimally invasive surgical strategies, such as transgastric 
endoscopic necrosectomy or videoassisted retroperitoneal 
debridement (VARD), result in less postoperative new-onset organ 
failure but require more interventions (1B).

Considering mortality, there is insufficient evidence to support open 
surgical, mini-invasive, or endoscopic approach (1B).

In selected cases with walled-off necrosis and in patients with 
disconnected pancreatic duct, a single stage surgical transgastric 
necrosectomy is an option (2C).
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coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 

A multidisciplinary group of experts should individualize surgical 
treatment taking local expertize into account (2C)
22. Timing of 
cholecystectomy

Laparoscopic cholecystectomy during index admission is 
recommended in mild acute gallstone pancreatitis (1A).

When ERCP and sphincterotomy are performed during the index 
admission, the risk for recurrent pancreatitis is diminished, but same 
admission cholecystectomy is still advised since there is an increased 
risk for other biliary complications (1B).

In acute gallstone pancreatitis with peripancreatic fluid collections, 
cholecystectomy should be deferred until fluid collections resolve or 
stabilize and acute inflammation ceases (2C).
23. Open abdomen

In patients with severe acute pancreatitis unresponsive to 
conservative management of IAH/ ACS, surgical decompression and 
use of open abdomen are effective in treating the abdominal 
compartment syndrome (2C).

We suggest that clinicians should be cautious not to over-resuscitate 
patients with early SAP and measure intra-abdominal pressure 
regularly (1C).

We suggest that the open abdomen (OA) be avoided if other 
strategies can be used to mitigate or treat severe intra-abdominal 
hypertension in SAP (1C).

We recommend not to utilize the OA after necrosectomy for SAP 
(unless severe IAH mandates OA as a mandatory procedure) (1C).

We recommend not to debride or undertake early necrosectomy if 
forced to undertake an early OA due abdominal compartment 
syndrome or visceral ischemia (1A).
24. Open abdomen 
management and 
temporary abdominal 
closure

We recommend the use of negative pressure peritoneal therapy for 
OA management (1B).

We suggest fascial traction be added to NPWT methods (2B).

We suggest that further controlled studies be conducted on intra-
peritoneal osmotic therapies in SAP (no recommendation)
25. Timing of dressing 
changes

Open abdomen re-exploration should be conducted no later than 24–
48 h after the index and any subsequent operation, with the duration 
from the previous operation shortening with increasing degrees of 
patient non-improvement and hemodynamic instability (1C).
26. Timing for 
abdominal closure

Early fascial and/or abdominal definitive closure should be the 
strategy for management of the open abdomen once any requirements 
for on-going resuscitation have ceased, the source control has been 
definitively reached, no concern regarding intestinal viability persist, 
no further surgical re-exploration is needed, and there are no 
concerns for abdominal compartment syndrome (1B).
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coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 
From: Leppäniemi A, Tolonen M, Tarasconi A, Segovia-Lohse H, Gamberini E, Kirkpatrick AW, Ball 
CG, Parry N, Sartelli M, Wolbrink D, van Goor H, Baiocchi G, Ansaloni L, Biffl W, Coccolini F, Di 
Saverio S, Kluger Y, Moore E, Catena F. 2019 WSES guidelines for the management of severe acute 
pancreatitis. World J Emerg Surg. 2019 Jun 13;14:27. doi: 10.1186/s13017-019-0247-0. PMID: 
31210778; PMCID: PMC6567462.
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coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 
Table_2. Statements and Recommendations from the 2005 UK guidelines for the management of 
Acute Pancreatitis.
1. Diagnosis

The correct diagnosis of acute pancreatitis should be made in all 
patients within 48 hours of admission (recommendation grade C). 

The etiology of acute pancreatitis should be determined in at least 80% 
of cases and no more than 20% should be classified as idiopathic 
(recommendation grade B). 

Although amylase is widely available and provides acceptable 
accuracy of diagnosis, where lipase estimation is available it is 
preferred for the diagnosis of acute pancreatitis (recommendation 
grade A). 

Where doubt exists, imaging may be used: ultrasonography is often 
unhelpful and pancreatic imaging by contrast enhanced computed 
tomography provides good evidence for the presence or absence of 
pancreatitis (recommendation grade C). 
2. Assessment

The definitions of severity, as proposed in the Atlanta criteria, should 
be used. However, organ failure present within the first week, which 
resolves within 48 hours, should not be considered an indicator of a 
severe attack of acute pancreatitis (recommendation grade B). 

Available prognostic features which predict complications in acute 
pancreatitis are clinical impression of severity, obesity, or APACHE 
II>8 in the first 24 hours of admission, and C reactive protein>150 
mg/l, Glasgow score 3 or more, or persisting organ failure after 48 
hours in hospital (recommendation grade B). 

Patients with persisting organ failure, signs of sepsis, or deterioration 
in clinical status 6– 10 days after admission will require computed 
tomography (recommendation grade B). 
3. Prevention of 
complications

The evidence to enable a recommendation about antibiotic prophylaxis 
against infection of pancreatic necrosis is conflicting and difficult to 
interpret. Some trials show benefit, others do not. At present there is no 
consensus on this issue. 

If antibiotic prophylaxis is used, it should be given for a maximum of 
14 days (recommendation grade B). Further studies are needed 
(recommendation grade C).

The evidence is not conclusive to support the use of enteral nutrition in 
all patients with severe acute pancreatitis. However, if nutritional 
support is required, the enteral route should be used if that can be 
tolerated (recommendation grade A). 
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coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 

The nasogastric route for feeding can be used as it appears to be 
effective in 80% of cases (recommendation grade B). 
4. Treatment of 
gallstones

Urgent therapeutic endoscopic retrograde cholangiopancreatography 
(ERCP) should be performed in patients with acute pancreatitis of 
suspected or proven gallstone etiology who satisfy the criteria for 
predicted or actual severe pancreatitis, or when there is cholangitis, 
jaundice, or a dilated common bile duct. The procedure is best carried 
out within the first 72 hours after the onset of pain. All patients 
undergoing early ERCP for severe gallstone pancreatitis require 
endoscopic sphincterotomy whether or not stones are found in the bile 
duct (recommendation grades B and C). 

Patients with signs of cholangitis require endoscopic sphincterotomy or 
duct drainage by stenting to ensure relief of biliary obstruction 
(recommendation grade A). 

All patients with biliary pancreatitis should undergo definitive 
management of gallstones during the same hospital admission, unless a 
clear plan has been made for definitive treatment within the next two 
weeks (recommendation grade C). 
5. Management of 
necrosis

All patients with severe acute pancreatitis should be managed in a high 
dependency unit or intensive therapy unit with full monitoring and 
systems support (recommendation grade B). 

All patients with persistent symptoms and greater than 30% pancreatic 
necrosis, and those with smaller areas of necrosis and clinical 
suspicion of sepsis, should undergo image guided fine needle 
aspiration to obtain material for culture 7–14 days after the onset of 
pancreatitis (recommendation grade B). 

Patients with infected necrosis will require intervention to completely 
debride all cavities containing necrotic material (recommendation 
grade B). 

The choice of surgical technique for necrosectomy, and subsequent 
postoperative management, depends on individual features and locally 
available expertise (recommendation grade B). 
6. Provision of 
services

Every hospital that receives acute admissions should have a single 
nominated clinical team to manage all patients with acute pancreatitis 
(recommendation grade C). 

Management in, or referral to, a specialist unit is necessary for patients 
with extensive necrotising pancreatitis or with other complications who 
may require intensive therapy unit care, or interventional radiological, 
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endoscopic, or surgical procedures (recommendation grade B). 
From: Working Party of the British Society of Gastroenterology; Association of Surgeons of Great 
Britain and Ireland; Pancreatic Society of Great Britain and Ireland; Association of Upper GI Surgeons 
of Great Britain and Ireland. UK guidelines for the management of acute pancreatitis. Gut. 2005 
May;54 Suppl 3(Suppl 3):iii1-9. doi: 10.1136/gut.2004.057026. PMID: 15831893; PMCID: 
PMC1867800.
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coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 
Table_3. Statements and Recommendations from the 2018 American Gastroenterological 
Association Institute Guideline on Initial Management of Acute Pancreatitis.
1. 

Recommendation 1A. In patients with AP, the AGA suggests using goal-directed 
therapy for fluid management. Conditional recommendation, very low quality 
evidence. Comment: The AGA makes no recommendation whether normal saline or 
Ringer’s lactate is used. 

Recommendation 1B. In patients with AP, the AGA suggests against the use of 
hydroxyethyl starch (HES) fluids. Conditional recommendation, very low quality 
evidence. 
2.

Recommendation 2. In patients with predicted severe AP and necrotizing pancreatitis, 
the AGA suggests against the use of prophylactic antibiotics. Conditional 
recommendation, low quality evidence. 
3. 

Recommendation 3. In patients with acute biliary pancreatitis and no cholangitis, the 
AGA suggests against the routine use of urgent ERCP. Conditional recommendation, 
low quality evidence. 
4. 

Recommendation 4. In patients with AP, the AGA recommends early (within 24 
hours) oral feeding as tolerated rather than keeping the patient nil per os. Strong 
recommendation; moderate quality evidence. 
5. 

Recommendation 5. In patients with AP and inability to feed orally, the AGA 
recommends enteral rather than parenteral nutrition. Strong recommendation, 
moderate quality evidence. 
6. 

Recommendation 6. In patients with predicted severe or necrotizing pancreatitis 
requiring enteral tube feeding, the AGA suggests either nasogastric or nasoenteral 
route. Conditional recommendation, low quality evidence. 
7.

Recommendation 7. In patients with acute biliary pancreatitis, the AGA recommends 
cholecystectomy during the initial admission rather than after discharge. Strong 
recommendation, moderate quality evidence. 
From: Crockett SD, Wani S, Gardner TB, Falck-Ytter Y, Barkun AN; American Gastroenterological 
Association Institute Clinical Guidelines Committee. American Gastroenterological Association 
Institute Guideline on Initial Management of Acute Pancreatitis. Gastroenterology. 2018 
Mar;154(4):1096-1101. doi: 10.1053/j.gastro.2018.01.032. Epub 2018 Feb 3. PMID: 29409760.
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coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 
Table_4. Statements and Recommendations from the 2015 Japanese guidelines for the 
management of acute pancreatitis.
1. Diagnosis

The measurement of serum lipase is recommended for the diagnosis of 
acute pancreatitis. However, when the measurement of lipase is difficult, 
serum amylase (pancreatic amylase) should be measured. (1B)

2 Urinary trypsinogen-2 dipstick may be useful for minimally invasive 
method and rapid diagnosis of acute pancreatitis. However, this is not 
commercially available in Japan and therefore it cannot be recommended 
at this time. (ungraded B)
2. Diagnostic 
imaging 

When acute pancreatitis is suspected, ultrasonography is recommended. 
(1C)

CT is recommended for the diagnosis of acute pancreatitis. (1C)

MRI is more useful than CT in diagnosing bile duct stones causing 
pancreatitis and hemorrhagic necrotizing pancreatitis. (2C)

Contrast-enhanced CT is useful for the diagnosis of active hemorrhage and 
thrombosis associated with pancreatitis. (1C)
3. Etiology

During etiological diagnosis, the diagnosis of gallstone-induced acute 
pancreatitis should be determined as the most important and urgent issue, 
as this greatly affects the treatment, such as whether endoscopic papillary 
treatment should be performed or not. (1A)
4. Severity 
assessment

In principle, it is recommended that a severity assessment be made 
immediately after diagnosis and repeated over time (especially within 48 h 
of the diagnosis). (1C)

It is recommended that a scoring system is used for severity assessments. 
(1B)

Contrast-enhanced CT is recommended for identifying poorly contrasted 
areas of acute pancreatitis and is also useful in the diagnosis of 
complications. However, the possibility of exacerbating pancreatitis and 
renal function and allergic reactions associated with the contrast must be 
considered. (2B)
5. Transfer 
indication 

Severe cases should be treated immediately at a facility capable of 
providing treatment for severe acute pancreatitis. Where such treatment is 
difficult at the facility, it is strongly recommended that the consideration 
be given to the immediate transfer of the patient. Even where the case is 
mild in the early stages, severity assessments should be carried out 
repeatedly over time, and when the criteria are met, transfer should be 
considered. (1C)
6. Fluid therapy

An extracellular solution (Ringer’s Lactate solution, etc.) is recommended 
as the initial infusion solution for acute pancreatitis. (1C)

For patients in shock or with dehydration in the early phases of acute 
pancreatitis, short-time rapid fluid resuscitation (150–600mL/h depending 
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coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 
on the presence of shock and the dehydration level) is recommended. 
However, this should be carried out with great care in order to avoid 
excessive fluid infusion. For patients without dehydration, they should be 
monitored closely with an appropriate amount of fluid infusion (130–
150mL/h). Particularly for patients with comorbidities such as cardiac or 
renal failure, the circulating blood volume should be careful evaluated to 
determine the rate of fluid infusion. (1C)

If a mean arterial pressure of 65mmHg or more and a urine output of 
0.5mL/kg per h or more has been secured in patients with acute 
pancreatitis, rapid fluid infusion should be discontinued and a reduction of 
the rate of fluid infusion is suggested. The volume of infusion should be 
adjusted to maintain these levels. (2C)
7. Nasogastric tube

No remedial effect of nasogastric tube insertion has been observed for 
mild acute pancreatitis. Therefore, the routine use of nasogastric suction 
tubes is not required. (1A)
8. Pain control 

Pain associated with acute pancreatitis is severe and persistent, raising the 
need of sufficient pain control. (1A)
9. Antibiotics 
prophylaxis

The prophylactic administration of antibiotics is not necessary in mild 
acute pancreatitis, since the incidence and mortality rates of infectious 
complications from mild acute pancreatitis are low. (1A)

The prophylactic administration of antibiotics in severe acute pancreatitis 
and necrotizing pancreatitis may improve the prognosis, if carried out in 
the early phases of pancreatitis (within 72 h of onset). (2B)

No remedial effect of the prophylactic administration of antifungal agents 
for acute pancreatitis has been observed. Therefore, routine administration 
is not recommended. (1C)
10. Protease 
inhibitor

The effectiveness of intravenous administration of protease inhibitor 
(gabexate mesilate) for improving the life prognosis and the rate of 
complications of acute pancreatitis has not been clearly proven. Further 
consideration of the efficacy of continuous high-dose intravenous 
administration for severe cases is required. (ungraded B)
11. Nutritional 
support 

Intravenous hyperalimentation is not recommended for mild cases. (1B)

Total parenteral nutrition (not performed with oral or enteral nutrition) 
should be avoided if possible. (1B)

In severe cases, it is more significant as a measure to prevent infection 
rather than as a route of nutrition support. It can be applied and 
implemented for severe cases which do not have accompanying intestinal 
complications. (1A)

If initiated in the early phase, enteral nutrition can reduce the incidence of 
complications and can contribute to an increased rate of survival. 
Therefore, it is desirable that it be started within at least 48 h of admission. 
(2A)
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coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 

In principle, it is recommended that enteral feeding tubes be inserted into 
the jejunum through the Treitz ligament. However, if a feeding tube 
cannot be inserted into the jejunum, nutrients can be infused into the 
duodenum or stomach instead. (2B)

The initiation of oral administration should be determined using indicators 
such as the subsidence of abdominal pain and the serum pancreatic 
enzyme (especially serum lipase) level, etc. (2B)
12. Intensive care

No life-saving effect has been observed from peritoneal lavage for acute 
pancreatitis, and therefore it is not recommended. (2B)

For severe cases where circulation dynamics are not stable with anuria 
even after sufficient initial fluid infusion or cases with abdominal 
compartment syndrome (ACS), CHF/CHDF should be introduced. (1C)

The efficacy of CHF/CHDF in cases of severe acute pancreatitis not 
mentioned above is uncertain. Therefore, routine use is not recommended. 
(2C)

Continuous Regional Arterial Infusion therapy is reported to be effective 
in reducing pancreatic infection and mortality rates for severe acute 
pancreatitis and acute necrotizing pancreatitis, but its efficacy has not been 
confirmed. (ungraded B)
13. Management 
of biliary 
pancreatitis

Early ERCP/ES should be performed in gallstone-induced acute 
pancreatitis when complications of cholangitis or prolonged passage 
disorder of the biliary tract are suspected. (1A)

To prevent the recurrence of gallstone-induced acute pancreatitis, 
cholecystectomy is recommended for cases where such surgery is 
possible. (1B)

A cholecystectomy should be performed as soon as gallstone-induced 
acute pancreatitis has been resolved. (1B)
14.  Management 
of abdominal 
compartment 
syndrome

The sequential measurement of IAP is recommended for cases with 
excessive fluid infusion, high severity, renal and respiratory 
complications, and fluid accumulation in multiple areas as observed by 
CT, since the onset of ACS increases the mortality rate in such cases. (2C)

When there is persistent or recurrent IAP≧12mmHg, conservative 
treatment (gastrointestinal decompression, intra-abdominal 
decompression, improvement of abdominal wall compliance, appropriate 
fluid infusion and circulation management) should be initiated. The goal 
should be to manage for IAP≦15mmHg. Surgical decompression should 
be considered only when internal treatment is not effective for patients 
with IAP>20mmHg and where the additional complication of organ failure 
is of concern. (2D)
15. Interventions 
for the local 
complications

In principle, conservative treatment should first be performed for 
necrotizing pancreatitis. The best indication for intervention is applied to 
cases of infected pancreatic necrosis with suspected or confirmed infection 
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accompanying an aggravated general condition. (1C)

Infected pancreatic necrosis should be suspected when clinical symptoms 
and blood test findings deteriorate. Routine use of FNA is not required for 
diagnosis, and clinical signs and CT should be used for a comprehensive 
determination. If an aggravated general condition is observed, 
percutaneous drainage or endoscopic drainage should be given for 
diagnosis and treatment. (1C)

If possible, therapeutic intervention for infected pancreatic necrosis should 
be performed after 4 weeks of onset, when the necrosis has been 
sufficiently walled off, or in other words, during WON period. (2C)

During therapeutic intervention for infected pancreatic necrosis, 
percutaneous (retroperitoneal) drainage or endoscopic transluminal 
drainage should be first given, and if no improvement is achieved, 
necrosectomy should then be performed. Necrosectomy by endoscopic or 
retroperitoneal approach is recommended. (2B)
16. Post-ERCP 
pancreatitis

Prophylactic temporary pancreatic stent placement is useful as an effective 
endoscopic procedure for the prevention of post-ERCP pancreatitis. This 
should only be performed in the high-risk groups for post-ERCP 
pancreatitis given the risks and cost. (2A)

The guidewire method is very likely to reduce the incidence of post-ERCP 
pancreatitis. (2A)

For the prevention of post-ERCP pancreatitis, the intrarectal 
administration of NSAIDs should be carried out for all cases undergoing 
ERCP with no contraindications. (2A)
(Other drugs should not be used as routine preventive measures, since their 
efficacy has been refuted or is uncertain.)
17. Clinical 
indicators 
(pancreatic 
bundles)

A high rate of implementation of the pancreatitis bundles may contribute 
to improving prognosis of patients with severe acute pancreatitis. (1C)
From: Yokoe M, Takada T, Mayumi T, Yoshida M, Isaji S, Wada K, Itoi T, Sata N, Gabata T, Igarashi 
H, Kataoka K, Hirota M, Kadoya M, Kitamura N, Kimura Y, Kiriyama S, Shirai K, Hattori T, Takeda 
K, Takeyama Y, Hirota M, Sekimoto M, Shikata S, Arata S, Hirata K. Japanese guidelines for the 
management of acute pancreatitis: Japanese Guidelines 2015. J Hepatobiliary Pancreat Sci. 2015 
Jun;22(6):405-32. doi: 10.1002/jhbp.259. Epub 2015 May 13. PMID: 25973947.
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coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 
Table_5: Statement and Recommendations from the AGA guidelines for the management of 
patients with pancreatic necrosis
BEST PRACTICE 
ADVICE 1
Pancreatic necrosis is associated with substantial morbidity and mortality and 
optimal management requires a multidisciplinary approach, including 
gastroenterologists, surgeons, interventional radiologists, and specialists in 
critical care medicine, infectious disease, and nutrition. In situations where 
clinical expertise may be limited, consideration should be given to transferring 
patients with significant pancreatic necrosis to an appropriate tertiary-care center. 
BEST PRACTICE 
ADVICE 2
Antimicrobial therapy is best indicated for culture-proven infection in pancreatic 
necrosis or when infection is strongly suspected (ie, gas in the collection, 
bacteremia, sepsis, or clinical deterioration). Routine use of prophylactic 
antibiotics to prevent infection of sterile necrosis is not recommended. 
BEST PRACTICE 
ADVICE 3
When infected necrosis is suspected, broad-spectrum intravenous antibiotics with 
ability to penetrate pancreatic necrosis should be favored (eg, carbapenems, 
quinolones, and metronidazole). Routine use of antifungal agents is not 
recommended. Computed tomography–guided fine-needle aspiration for Gram 
stain and cultures is unnecessary in the majority of cases. 
BEST PRACTICE 
ADVICE 4
In patients with pancreatic necrosis, enteral feeding should be initiated early to 
decrease the risk of infected necrosis. A trial of oral nutrition is recommended 
immediately in patients in whom there is absence of nausea and vomiting and no 
signs of severe ileus or gastrointestinal luminal obstruction. When oral nutrition 
is not feasible, enteral nutrition by either nasogastric/ duodenal or nasojejunal 
tube should be initiated as soon as possible. Total parenteral nutrition should be 
considered only in cases where oral or enteral feeds are not feasible or tolerated.
BEST PRACTICE 
ADVICE 5
Drainage and/or debridement of pancreatic necrosis is indicated in patients with 
infected necrosis. Drainage and/or debridement may be required in patients with 
sterile pancreatic necrosis and persistent unwellness marked by abdominal pain, 
nausea, vomiting, and nutritional failure or with associated complications, 
including gastrointestinal luminal obstruction; biliary obstruction; recurrent acute 
pancreatitis; fistulas; or persistent systemic inflammatory response syndrome. 
BEST PRACTICE 
ADVICE 6
Pancreatic debridement should be avoided in the early, acute period (first 2 
weeks), as it has been associated with increased morbidity and mortality. 
Debridement should be optimally delayed for 4 weeks and performed earlier only 
when there is an organized collection and a strong indication. 
BEST PRACTICE 
ADVICE 7
Percutaneous drainage and transmural endoscopic drainage are both appropriate 
first-line, nonsurgical approaches in managing patients with walled-off pancreatic 
necrosis (WON). Endoscopic therapy through transmural drainage of WON may 
be preferred, as it avoids the risk of forming a pancreatocutaneous fistula. 
30

coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 
BEST PRACTICE 
ADVICE 8
Percutaneous drainage of pancreatic necrosis should be considered in patients 
with infected or symptomatic necrotic collections in the early, acute period (<2 
weeks), and in those with WON who are too ill to undergo endoscopic or surgical 
intervention. Percutaneous drainage should be strongly considered as an adjunct 
to endoscopic drainage for WON with deep extension into the paracolic gutters 
and pelvis or for salvage therapy after endoscopic or surgical debridement with 
residual necrosis burden. 
BEST PRACTICE 
ADVICE 9
Self-expanding metal stents in the form of lumen-apposing metal stents appear to 
be superior to plastic stents for endoscopic transmural drainage of necrosis. 
BEST PRACTICE 
ADVICE 10
The use of direct endoscopic necrosectomy should be reserved for those patients 
with limited necrosis who do not adequately respond to endoscopic transmural 
drainage using large-bore, self-expanding metal stents/lumen-apposing metal 
stents alone or plastic stents combined with irrigation. Direct endoscopic 
necrosectomy is a therapeutic option in patients with large amounts of infected 
necrosis, but should be per- formed at referral centers with the necessary 
endoscopic expertise and interventional radiology and surgical backup. 
BEST PRACTICE 
ADVICE 11
Minimally invasive operative approaches to the debridement of acute necrotizing 
pancreatitis are preferred to open surgical necrosectomy when possible, given 
lower morbidity. 
BEST PRACTICE 
ADVICE 12
Multiple minimally invasive surgical techniques are feasible and effective, 
including videoscopic-assisted retroperitoneal debridement, laparoscopic 
transgastric debridement, and open transgastric debridement. Selection of 
approach is best deter- mined by pattern of disease, physiology of the patient, 
experience and expertise of the multidisciplinary team, and available resources. 
BEST PRACTICE 
ADVICE 13
Open operative debridement maintains a role in the modern management of acute 
necrotizing pancreatitis in cases not amenable to less invasive endoscopic and/or 
surgical procedures. 
BEST PRACTICE 
ADVICE 14
For patients with disconnected left pancreatic remnant after acute necrotizing 
mid-body necrosis, definitive surgical management with distal pancreatectomy 
should be undertaken in patients with reasonable operative candidacy. 
Insufficient evidence exists to support the management of the disconnected left 
pancreatic remnant with long- term transenteric endoscopic stenting. 
BEST PRACTICE 
ADVICE 15
A step-up approach consisting of percutaneous drainage or endoscopic transmural 
drainage using either plas- tic stents and irrigation or self-expanding metal 
stents/lumen- apposing metal stents alone, followed by direct endoscopic 
necrosectomy, and then surgical debridement is reasonable, although approaches 
may vary based on the available clinical expertise. 
31

coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 
From: Baron TH, DiMaio CJ, Wang AY, Morgan KA. American Gastroenterological Association 
Clinical Practice Update: Management of Pancreatic Necrosis. Gastroenterology. 2020 Jan;158(1):67-
75.e1. doi: 10.1053/j.gastro.2019.07.064. Epub 2019 Aug 31. PMID: 31479658.
References
1. Krishna SG, Kamboj AK, Hart PA, Hinton A, Conwell DL. The Changing Epidemiology of Acute 
Pancreatitis Hospitalizations: A Decade of Trends and the Impact of Chronic Pancreatitis. Pancreas. 
2017 Apr;46(4):482-488. doi: 10.1097/MPA.0000000000000783. PMID: 28196021; PMCID: 
PMC5435121.
2. Koutroumpakis E, Slivka A, Furlan A, Dasyam AK, Dudekula A, Greer JB, Whitcomb DC, Yadav 
D, Papachristou GI. Management and outcomes of acute pancreatitis patients over the last decade: A 
US tertiary-center experience. Pancreatology. 2017 Jan-Feb;17(1):32-40. doi: 
10.1016/j.pan.2016.10.011. Epub 2016 Oct 24. PMID: 28341116.
3. Singh VK, Bollen TL, Wu BU, Repas K, Maurer R, Yu S, Mortele KJ, Conwell DL, Banks PA. An 
assessment of the severity of interstitial pancreatitis. Clin Gastroenterol Hepatol. 2011 Dec;9(12):1098-
103. doi: 10.1016/j.cgh.2011.08.026. Epub 2011 Sep 3. PMID: 21893128.
4. van Santvoort HC, Bakker OJ, Bollen TL, Besselink MG, Ahmed Ali U, Schrijver AM, Boermeester 
MA, van Goor H, Dejong CH, van Eijck CH, van Ramshorst B, Schaapherder AF, van der Harst E, 
Hofker S, Nieuwenhuijs VB, Brink MA, Kruyt PM, Manusama ER, van der Schelling GP, Karsten T, 
Hesselink EJ, van Laarhoven CJ, Rosman C, Bosscha K, de Wit RJ, Houdijk AP, Cuesta MA, Wahab 
PJ, Gooszen HG; Dutch Pancreatitis Study Group. A conservative and minimally invasive approach to 
necrotizing pancreatitis improves outcome. Gastroenterology. 2011 Oct;141(4):1254-63. doi: 
10.1053/j.gastro.2011.06.073. Epub 2011 Jul 8. PMID: 21741922.
5. Peery AF, Crockett SD, Barritt AS, Dellon ES, Eluri S, Gangarosa LM, Jensen ET, Lund JL, 
Pasricha S, Runge T, Schmidt M, Shaheen NJ, Sandler RS. Burden of Gastrointestinal, Liver, and 
32

coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 
Pancreatic Diseases in the United States. Gastroenterology. 2015 Dec;149(7):1731-1741.e3. doi: 
10.1053/j.gastro.2015.08.045. Epub 2015 Aug 29. PMID: 26327134; PMCID: PMC4663148.
6. Goodchild G, Chouhan M, Johnson GJ. Practical guide to the management of acute pancreatitis. 
Frontline Gastroenterol. 2019 Jul;10(3):292-299. doi: 10.1136/flgastro-2018-101102. Epub 2019 Mar 
2. PMID: 31288253; PMCID: PMC6583768.
7. Leppäniemi A, Tolonen M, Tarasconi A, Segovia-Lohse H, Gamberini E, Kirkpatrick AW, Ball CG, 
Parry N, Sartelli M, Wolbrink D, van Goor H, Baiocchi G, Ansaloni L, Biffl W, Coccolini F, Di 
Saverio S, Kluger Y, Moore E, Catena F. 2019 WSES guidelines for the management of severe acute 
pancreatitis. World J Emerg Surg. 2019 Jun 13;14:27. doi: 10.1186/s13017-019-0247-0. PMID: 
31210778; PMCID: PMC6567462.
8. Toh SK, Phillips S, Johnson CD. A prospective audit against national standards of the presentation 
and management of acute pancreatitis in the South of England. Gut. 2000 Feb;46(2):239-43. doi: 
10.1136/gut.46.2.239. PMID: 10644319; PMCID: PMC1727819.
9. Gurusamy KS, Farouk M, Tweedie JH. UK guidelines for management of acute pancreatitis: is it 
time to change? Gut. 2005 Sep;54(9):1344-5. doi: 10.1136/gut.2005.071076. PMID: 16099804; 
PMCID: PMC1774643.
10. Lankisch PG, Weber-Dany B, Lerch MM. Clinical perspectives in pancreatology: compliance with 
acute pancreatitis guidelines in Germany. Pancreatology. 2005;5(6):591-3. doi: 10.1159/000087501. 
Epub 2005 Aug 16. PMID: 16110257.
11. Cavallini G, Frulloni L, Bassi C, Gabbrielli A, Castoldi L, Costamagna G, De Rai P, Di Carlo V, 
Falconi M, Pezzilli R, Uomo G; ProInf-AISP Study Group. Prospective multicentre survey on acute 
pancreatitis in Italy (ProInf-AISP): results on 1005 patients. Dig Liver Dis. 2004 Mar;36(3):205-11. 
doi: 10.1016/j.dld.2003.11.027. PMID: 15046191.
33

coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 
12. Green R, Charman SC, Palser T. Early definitive treatment rate as a quality indicator of care in 
acute gallstone pancreatitis. Br J Surg. 2017 Nov;104(12):1686-1694. doi: 10.1002/bjs.10578. Epub 
2017 Aug 9. PMID: 28792589.
13. Tan JW, Gao Y, Kow AWC, Bonney G, Madhavan K, Windsor JA, Iyer SG. Clinical management 
and outcomes of acute pancreatitis: Identifying areas for quality improvement in a tertiary Asian 
setting. Pancreatology. 2019 Jun;19(4):507-518. doi: 10.1016/j.pan.2019.04.011. Epub 2019 Apr 30. 
PMID: 31088718.
14. Greenberg JA, Hsu J, Bawazeer M, Marshall J, Friedrich JO, Nathens A, Coburn N, Huang H, 
McLeod RS. Compliance with Evidence-Based Guidelines in Acute Pancreatitis: an Audit of Practices 
in University of Toronto Hospitals. J Gastrointest Surg. 2016 Feb;20(2):392-400. doi: 10.1007/s11605-
015-3023-9. Epub 2015 Nov 30. PMID: 26621675.
15. Jakobsen HL, Rosenberg J, Schulze S, Kristiansen VB. Behandlingen af galdestenspankreatitis i 
Danmark [Treatment of gallstone pancreatitis in Denmark]. Ugeskr Laeger. 2005 Jun 13;167(24):2651-
3. Danish. PMID: 16014225.
16. Pezzilli R, Uomo G, Gabbrielli A, Zerbi A, Frulloni L, De Rai P, Castoldi L, Cavallini G, Di Carlo 
V; ProInf-AISP Study Group. A prospective multicentre survey on the treatment of acute pancreatitis 
in Italy. Dig Liver Dis. 2007 Sep;39(9):838-46. doi: 10.1016/j.dld.2007.05.014. Epub 2007 Jun 29. 
PMID: 17602904.
17. Ragnarsson T, Andersson R, Ansari D, Persson U, Andersson B. Acute biliary pancreatitis: focus 
on recurrence rate and costs when current guidelines are not complied. Scand J Gastroenterol. 2017 
Mar;52(3):264-269. doi: 10.1080/00365521.2016.1243258. Epub 2016 Dec 9. PMID: 27700180.
18. Aly EA, Milne R, Johnson CD. Non-compliance with national guidelines in the management of 
acute pancreatitis in the United kingdom. Dig Surg. 2002;19(3):192-8. doi: 10.1159/000064212. 
PMID: 12119521.
34

coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 
19. Rebours V, Lévy P, Bretagne JF, Bommelaer G, Hammel P, Ruszniewski P. Do guidelines 
influence medical practice? Changes in management of acute pancreatitis 7 years after the publication 
of the French guidelines. Eur J Gastroenterol Hepatol. 2012 Feb;24(2):143-8. doi: 
10.1097/MEG.0b013e32834d864f. PMID: 22123707.
20. Baron TH, DiMaio CJ, Wang AY, Morgan KA. American Gastroenterological Association Clinical 
Practice Update: Management of Pancreatic Necrosis. Gastroenterology. 2020 Jan;158(1):67-75.e1. 
doi: 10.1053/j.gastro.2019.07.064. Epub 2019 Aug 31. PMID: 31479658.
21. Trikudanathan G, Wolbrink DRJ, van Santvoort HC, Mallery S, Freeman M, Besselink MG. 
Current Concepts in Severe Acute and Necrotizing Pancreatitis: An Evidence-Based Approach. 
Gastroenterology. 2019 May;156(7):1994-2007.e3. doi: 10.1053/j.gastro.2019.01.269. Epub 2019 Feb 
15. PMID: 30776347.
22. Lim CL, Lee W, Liew YX, Tang SS, Chlebicki MP, Kwa AL. Role of antibiotic prophylaxis in 
necrotizing pancreatitis: a meta-analysis. J Gastrointest Surg. 2015 Mar;19(3):480-91. doi: 
10.1007/s11605-014-2662-6. Epub 2015 Jan 22. PMID: 25608671.
23. Baltatzis M, Jegatheeswaran S, O'Reilly DA, Siriwardena AK. Antibiotic use in acute pancreatitis: 
Global overview of compliance with international guidelines. Pancreatology. 2016 Mar-Apr;16(2):189-
93. doi: 10.1016/j.pan.2015.12.179. Epub 2016 Jan 12. PMID: 26804006.
24. COVIDSurg Collaborative. Mortality and pulmonary complications in patients undergoing surgery 
with perioperative SARS-CoV-2 infection: an international cohort study. Lancet. 2020 Jul 
4;396(10243):27-38. doi: 10.1016/S0140-6736(20)31182-X. Epub 2020 May 29. Erratum in: Lancet. 
2020 Jun 9;: PMID: 32479829; PMCID: PMC7259900. 
25. Pandanaboyana S, Moir J, Leeds JS, Oppong K, Kanwar A, Marzouk A, Belgaumkar A, Gupta A, 
K Siriwardena A, Haque AR, Awan A, Balakrishnan A, Rawashdeh A, Ivanov B, Parmar C, M 
35

coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis (MANCTRA-1). 
Halloran C, Caruana C, Borg CM, Gomez D, Damaskos D, Karavias D, Finch G, Ebied H, K Pine J, R 
A Skipworth J, Milburn J, Latif J, Ratnam Apollos J, El Kafsi J, Windsor JA, Roberts K, Wang K, Ravi 
K, V Coats M, Hollyman M, Phillips M, Okocha M, Sj Wilson M, A Ameer N, Kumar N, Shah N, 
Lapolla P, Magee C, Al-Sarireh B, Lunevicius R, Benhmida R, Singhal R, Balachandra S, Demirli 
Atıcı S, Jaunoo S, Dwerryhouse S, Boyce T, Charalampakis V, Kanakala V, Abbas Z, Nayar M. 
SARS-CoV-2 infection in acute pancreatitis increases disease severity and 30-day mortality: COVID 
PAN collaborative study. Gut. 2021 Feb 5:gutjnl-2020-323364. doi: 10.1136/gutjnl-2020-323364. 
Epub ahead of print. PMID: 33547182.
36