Study design and participants
This was a retrospective, nested, case-control study with an analysis of patients with NP who were hospitalized in the Department of Gastroenterology of the First Affiliated Hospital of Nanchang University, a tertiary care referral center in China, from April 2015 to April 2020. We used data from a prospectively maintained database, which is a data repository for the clinical data of all AP patients admitted to our department, including diagnostic, therapeutic, and follow-up data recorded by a special research assistant.
Adult patients with NP who underwent endoscopic transmural drainage (ETD) and subsequent ETN were eligible. Patients who died or were transferred to open surgery were excluded due to the failure of stent removal and being grouped. All patients were followed up for at least three months after discharge, and patients who were lost to follow-up were excluded. All primary necrotic collections adherent to the stomach or duodenum were drained by ETD and subsequent ETN only. For necrotic collections not in communication with the primary collection, percutaneous drainage (PCD) and/or sinus tract endoscopy was adjunctively used. Patients whose primary collection was drained by both endoscopic and percutaneous approaches were excluded due to the confounding effect on the evaluation of the research results.
Case group (the novel strategy) and 1:1 necrosis extent matched control group (the conventional strategy) was nested in the retrospective cohort, and compared. The AP database was approved by the Ethics Committee of the First Affiliated Hospital of Nanchang University (N0: 2011001). Informed consent for the procedures was obtained from all the patients prior to the procedures. The ethics approval and written informed consent for using the data were waivered by the Ethics Committee of the First Affiliated Hospital of Nanchang University due to the retrospective nature of the study. All methods were performed in accordance with the relevant guidelines and regulations.
Interventions
All management decisions regarding interventions were made in a multidisciplinary team involving pancreatologists, endoscopists, surgeons, interventional radiologists, radiologists, and intensivists using our previously described algorithm.13,14 Patients enrolled in our study were managed using a strategy based on an endoscopically centered step-up approach. ETD was first optimal for primary necrotic collection adjacent to the stomach or duodenum, with subsequent ETN as required. Adjunctive PCD was typically performed for collections not amenable to endoscopic therapy due to a lack of contact with the gastric or duodenal wall, with subsequent sinus tract endoscopy as required. Open surgery was reserved for failure of the step-up approach or severe complications such as severe abdominal bleeding.
All patients underwent contrast-enhanced CT to determine the location and extent of the necrotic collections before the procedure. All patients were administered broad-spectrum antibiotics during and after the procedure to prevent infection. Patients underwent tracheal intubation and general anesthesia in the left lateral decubitus position. All of the interventions were performed by experienced gastroenterologists. A linear echoendoscope (Olympus GIF-H290, Tokyo, Japan) was used to examine and assess the necrotic collections. The puncture path was oriented according to the principle of making the distance between the digestive wall and the necrotic collections shortest and avoiding blood vessels. Under ultrasound endoscopic guidance, a COOK 19-G needle was used to puncture the necrotic collections, and then the fluid was aspirated for microbiology, biochemical testing and routine examination.
If a patient did not have clinical improvement or resolution of necrotic fluid, ETN was performed as needed after initial ETD, typically within 3 to 5 days after drainage for patients with IPN or organ failure, or later for patients with less acute illness and/or primarily liquified collections. All ETNs in our cohort were delayed up to 4 weeks after AP onset to allow for the development of a wall around the necrosis, which was consistent with the recommendations of the newest guideline.8 ETN was repeated as needed based on the clinical course and until there was complete resolution of solid necrosis. The endpoint of ETN was achieved when the necrotic tissue was nearly completely removed and the pink granulation tissue lining the wall was uncovered. There were two strategies for stent removal: In the novel strategy, the stents were removed during the last necrosectomy when the endpoint of ETN was achieved (Case group). In the conventional strategy, a CT scan was performed to assess the resolution of fluid and whether the stents were in place within 4 weeks after stent placement. The stent was removed when clinical symptoms were relieved and fluid was nearly completely resolved (Control group). Compared to the conventional strategy, the novel strategy avoided one endoscopy procedure.
Outcomes of interest and data collection
The primary outcome of interest was the number of additional ETN sessions after stent removal. The secondary outcomes included clinical success and disease- or stent-related complications, as well as the length of hospital stay. Clinical success was defined as nearly completely resolution or <2 cm of collection assessed by image at the three-month follow-up without additional open surgery or death.13,14 Disease-related complications included new-onset organ failure, transient fever, new-onset infection, abdominal or gastrointestinal bleeding, or gastrointestinal fistula. Stent-related complications included stent occlusion and migration. Other rare complications were not observed in our cohort. Organ failure included respiratory failure, circulatory failure or renal failure, which was defined as a score of 2 or more using the modified Marshall scoring system.15,16 Transient fever meant low fever (usually <38 ℃), which persisted for 3-5 days without culture positivity. IPN was confirmed by extraluminal gas in the pancreatic and/or peripancreatic tissues on contrast-enhanced CT or positive bacteria and/or fungi on Gram stain or culture of pancreatic and/or peripancreatic tissues obtained from the first drainage procedure or the first necrosectomy.15 Abdominal or gastrointestinal bleeding was defined as severe bleeding requiring intervention along with decreased hemoglobin, and this complication was examined by imaging. The other detailed records, including baseline characteristics, indications, and interventions, were also analyzed.
Statistical analysis
Quantitative variables are presented as medians (interquartile ranges (IQR)) and were analyzed using the Mann-Whitney U test. Categorical variables are reported as absolute numbers and proportions and were tested by the Chi-square test or Fisher’s exact test. P<0.05 was considered statistically significant. Data were analyzed using SPSS software (v17.0; SPSS Inc., Chicago, IL, USA).