A Tailored Step-up Approach for Moderate to Critical Acute Pancreatitis in the Late Phase: a Cohort Study
Conditions: Acute Pancreatitis
Sponsor: University of Pisa

A “TAILORED” STEP-UP APPROACH FOR MODERATE TO CRITICAL 
ACUTE PANCREATITIS IN LATE PHASE: A COHORT STUDY 
 
Running Title: Late phase acute pancreatitis: a tailored step-up approach 
Document date: 31/03/2021 
Manuscript type: Original article 
Word count of entire article:  3887 
Figures: 4 
 
 

Study Protocol 
The Investigators retrospectively analyzed data of all patients treated at our referral Center for 
moderate to critical AP, as classified by Determinant-Based Classification of Acute Pancreatitis Severity 
(DBC). Patients treated with interventional or surgical procedures after 4 weeks (late phase) were 
included in the study, while patients who had undergone conservative treatment, or who has been 
operated within 4 weeks (early phase) were excluded from the data analysis.  
The cohort sample was divided into four groups, according to the first type of the interventional or 
surgical management performed: percutaneous drainage group (PD), endoscopic approach group 
(END), surgical internal derivation of WON group (INT), and surgical necrosectomy group (NE). In 
all cases, the decision to intervene with an invasive procedure was taken on the basis of a clinical course 
not responsive to conservative management, signs of sepsis due to infected necrosis, or persistent 
gastric output obstruction with large fluid collections. The operative approach was chosen based on our 
experience and on the current Literature evidence, using a “tailored” step-up approach. 
The acute pancreatitis severity was retrospectively graded according to the DBC, based on data drawn 
from clinical records. 
 
All the procedures had been performed by surgeons, gastroenterologists/endoscopists, or 
interventional radiologists who composed the multidisciplinary group.  
In performing primary PD, catheters up to 16 Fr were inserted using Seldinger technique, guided by 
ultrasound (US) or Computer Tomography (CT).  
In the END approach, a lumen apposing HOT AXIOS™ (Boston Scientific, Boston, MA, USA) 15 x 
10 mm metal stent was placed trans-luminally by echo-endoscopic guidance, under conscious sedation. 
The procedure was completed with the insertion of a naso-cystic catheter to facilitate liquefaction of 
debris. Further endoscopic sessions and trans-luminal necrosectomy were considered case by case. 
Surgical internal derivation throughout gastric or enteric breach, adopted since 2014, was considered in 
the case of WON with mature walls. When the WON was not adjacent to the stomach or showed 
necrosis in its inferior portion, the enteric Roux-en-Y derivation was selected. However, in the vast 
majority of cases, trans-gastric necrosectomy and internal derivation were carried out. Firstly, a US-
guided anterior gastrotomy was performed. Then, large communication up to 80 mm was created 
between WON and the posterior gastric wall using a mechanical stapler; finally, the necrotic debris was 
removed from the WON’ cavity. At our Center, since 2017, a minimally invasive variant of this 

approach has been performed using the da Vinci Xi robot (Intuitive Surgical Inc., Sunnyvale, CA, 
USA). 
The NE was performed either in case of failure of endoscopic/percutaneous drainage or as a first-line 
treatment. It was accomplished by standard trans-peritoneal laparotomy and continuous post-operative 
lavage or by retroperitoneal US-guided mini-laparotomic approach, depending on the distribution of 
the necrotic tissue. When it was applicable, the infra-mesocolic approach was preferred. The standard 
trans-peritoneal NE was performed in a supine position. The retroperitoneal US-guided mini-
laparotomic approach was performed in lateral decubitus: the US-guidance allowed to perform a 
focused right or left flank mini-laparotomy, and to obtain complete debridement using long 
instruments, through the retroperitoneal way. 
The following variables were evaluated: sex, age, severity of inflammation according to the DBC 
classification, PA etiology, CT scan severity index according to Balthazar criteria, clinical prognostic 
score using bedside index of severity of acute pancreatitis (BISAP) score.   
Total length of hospitalization, operative management, necrosis cultures, total and post-interventional 
Intensive Unit Care (ICU) were also recorded and analyzed together with the in-hospital morbidity, 
mortality and re-admissions. 
Patients were checked after discharge within 14 days and followed monthly as outpatients by 
gastroenterologists. A CT scan was performed within 4 months, or before in case of recurrent 
symptoms. During the follow-up, the English Standard Short Form 36 (SF-36) questionnaire was used 
to evaluate the general quality of life at three and six months, one and two years. The SF-36 examines 8 
areas consisting of social and physical function, physical and emotional well-being, bodily pain, vitality, 
mental health and overall general health perception. At the six-month follow-up, the patients also 
completed a specific questionnaire about the pancreatic function [10]. In particular, the total score takes 
in consideration abdominal pain using visual analogue pain score, diarrhea, unintentional weight loss, 
new onset of diabetes and use of enzyme supplementation. The score ranges between zero to five (all 
symptoms present). 
The work has been reported in line with the STROCSS criteria. 
Statistical analysis 
For the data analysis, the Chi-square test was used to define associations between categorical factors 
and surgical groups. Continuous variables with normal distribution were expressed as mean ± standard 
deviation (SD) and compared using the ANOVA test. Variables with an abnormal distribution were 
expressed as median and compared using the Kruskal-Wallis Test. A p-value ≤ 0.05 was considered 

statistically significant. The statistical analysis was performed using SPSS (Statistical Production and 
Service Solution for Windows, SPSS Inc., Chicago, IL, USA), version 24. 
 
 
 
All procedures performed in studies involving human participants were in accordance with the ethical 
standards of the institutional and/or national research committee and with the 1964 Helsinki 
declaration and its later amendments or comparable ethical standards. For this type of study, formal 
consent is not required