In this study, we combined PEN and TN and proposed a novel step-up approach to the treatment of extensive IPN in patients with SAP. The patients enrolled in our study were severely ill, as evidenced by the high APACHE II and SOFA scores, and had extensive pancreatic/peripancreatic necrosis, as indicated by the CTSI score. Despite this, they were successfully managed with this integrated mini-invasive strategy without serious complications and avoided further open necrosectomy.
The surgical step-up approach, which initially involves PCD followed by VARD or endoscopic necrosectomy through the percutaneous sinus tract, was found to be superior to open necrosectomy5,14. The PANTER study prospectively enrolled 88 patients with necrotizing pancreatitis, 24 of whom underwent percutaneous drainage and VARD; The results showed that the incidence of new-onset multiple organ failure, incisional hernias, and new-onset diabetes was significantly lower in patients treated with the surgical step-up approach than in those treated with open necrosectomy, although mortality did not differ between the two groups5. Liu et al. conducted a retrospective cohort study involving 27 patients with IPN suffering from failure PCD, 15 of whom subsequently underwent double-catheter lavage and PEN, and 12 underwent open necrosectomy14. The authors concluded that the rate of new-onset multiple organ failure and the length of ICU stay were significantly lower in the PEN group than in the open necrosectomy group. The surgical step-up approach is ideal for treating patients with lateral fluid collections or necrosis that extends into the paracolic gutters, the pararenal space, and the pelvis, while the endoscopic step-up approach is suitable for patients with medial fluid collections or necrosis, that is, fluid collections or necrosis confined to the vicinity of the gastroduodenal location, such as the posterior gastric space and the lower sac. The endoscopic transgastric approach presents a lower risk of pancreatic fistula and a shorter hospital and ICU stay than surgical necrosectomy15. However, only a few clinical studies have compared these two mini-invasive step-up approaches, and even fewer have reported on their combination. The PENGUIN trial prospectively enrolled 20 patients with IPN; endoscopic transgastric necrosectomy was performed in 10 patients, and VARD or open necrosectomy was performed in another 10 patients7. The results showed that the former technique can further reduce the level of serum interleukin 6 and major complications, including new-onset multiple organ failure and pancreatic fistula. However, this result should be interpreted with caution due to the small sample size. Van Brunschot et al. conducted a randomized clinical trial investigating the endoscopic vs. surgical step-up approach in a cohort of 98 patients with necrotizing pancreatitis, who were randomly assigned to the two treatment arms10. The authors found that the main complications, including bleeding, perforation of the visceral organs, enterocutaneous fistula, and incisional hernia, and mortality rates did not differ between the two groups, although the incidence of pancreatic fistula and length of hospital stay were lower in the endoscopic step-up approach group. The same group published another large sample study involving 1980 patients with original study data and unpublished data to compare mini-invasive surgical, endoscopic, and open necrosectomy for the treatment of necrotizing pancreatitis16. The authors used propensity score matching with risk stratification to control possible confounders and found that both mini-invasive surgical and endoscopic necrosectomy were associated with a lower risk of death than open necrosectomy in the very high-risk group (predicted risk of death ≥ 35%). Furthermore, the effect of mini-invasive surgical necrosectomy on mortality was not different from that of endoscopic necrosectomy.
In 2016, Fagenholz et al. first reported a case of extensive pancreatic necrosis complicated by enteric fistulae successfully treated using transgastric drainage combined with the VARD method17. Sorrentino et al. subsequently reported a patient with central walled-off pancreatic necrosis extending laterally to the bilateral retroperitoneal spaces complicated by multiorgan failure and choledochal fistula18. The patient was successfully treated using a combined mini-invasive approach, including endoscopic transgastric necrosectomy, PCD, VARD, and endoscopic biliary stenting. In 2022, Lindgaard et al. described two patients with large and complex walled-off pancreatic necrosis who underwent endoscopic transluminal drainage, endoscopic necrosectomy, and VARD using a laparoscopic access platform19. After 34 days and 86 days of treatment and a total of 9 and 14 procedures, respectively, the walled-off pancreatic necrosis completely regressed in both cases.
There are five aspects of this approach that require further exploration. First, both PEN and TN have their individual application indications; this combined approach is suitable for patients with extensive necrosis, especially those with medial and lateral necrosis. Second, there is no relevant research on the timing and sequence of implementation of these two necrosectomy technologies. Despite this, we advocate the surgical step-up approach as a priority for patients with extensive IPN. The literature reports that approximately 13.6–17.0% of patients with SAP die in the early stages (first 2 weeks) due to excessive systemic inflammatory response syndrome and organ dysfunction20,21. Early administration of PCD to relieve the systemic inflammatory response and improve organ function, followed by PEN through the sinus tract, has become the most common approach in clinical practice22,23. Furthermore, critically ill patients, especially unstable patients, are more tolerant to this approach than to the transgastric approach. More importantly, this also provides sufficient time for the formation of walled-off necrosis. Until then, TN could carry a high risk of pneumoperitoneum or pneumoretroperitoneum, which may result in infective complications24. Third, the CNPI was a bridge between PCD and PEN in our mini-invasive step-up approach. In recent years, large-bore percutaneous drainage tubes placed using the Seldinger technique and large-volume irrigation have been reported for the treatment of necrotizing pancreatitis23,25. On the one hand, continuous lavage with 0.9% saline solution may provide a gentle way to clear the infection, thus improving necrosis cavity healing26,27. Conversely, negative pressure treatment has been proven to be effective in removing necrotic debris and preventing re-accumulation of purulence in the wound bed, resulting in increased epithelial regeneration and granulation tissue coverage in the wound28,29. Furthermore, Gao et al. performed a retrospective analysis of 132 patients with IPN and colonic fistula who received a step-up approach including CNPI and found that the approach could avoid the need for subsequent surgery in 47% of patients, spontaneous closure of the fistula in 92% of patients, and in-hospital mortality fell to only 19%30. The scavenging effect of CNPI on necrosis caused the frequency of PEN (range, 1–2) to be lower than that of TN (range, 2–4) in our study, resulting in a lower risk of external fistula formation. Fourth, TN was performed with LAMS in all our patients due to its large diameter (15 mm) and bi-flanged design, which facilitates endoscopic transluminal necrosectomy, reduces the risk of stent occlusion, and prevents stent migration. A large retrospective study enrolled 189 patients with pancreatic walled-off necrosis who underwent EUS-guided transmural drainage, of whom 102 had LAMS and 87 had plastic stent, respectively31. Patients with LAMS had a higher clinical success rate, shorter procedure time, and a lower probability of requiring surgery and recurrence than those with plastic stents. However, two recent prospective studies evaluating the clinical effects and associated complications of LAMS have shown mixed results32,33. In a randomized controlled trial by Bang et al. involving 60 patients with pancreatitis and walled-off necrosis, patients with LAMS had similar technical success, treatment success, and the total number of procedures performed during the 6 months of follow-up was comparable to that obtained following placement of plastic stents32. However, the endoscopic operation time was shorter in patients with LAMS despite the higher incidence of complications and costs. In contrast, another prospective cohort study enrolled 53 patients with IPN and found that the number of endoscopic transluminal necrosectomy procedures, incidence of complications, and total healthcare costs were comparable between the two stents33. The results of two ongoing randomized controlled studies will further evaluate the clinical efficacy and possible complications34,35; however, shorter endoscope operation times with LAMS are unambiguously evident, which is a potentially crucial advantage for more critical cases12,32. Finally, approximately 27–32% of patients with IPN who underwent the endoscopic step-up approach required additional PCD procedures10,33. This may be due to the destruction of the well-defined necrosis wall associated with the endoscopic transluminal procedure, which results in the spread of necrosis, digestive enzymes, and pro-inflammatory mediators to other parts of the abdominal cavity. Furthermore, the endoscopic transluminal procedure also causes loss of retroperitoneal compartmentalization, leading to spread of necrosis into communicating recesses and cavities. Some studies have reported the use of a dual modality, which refers to the administration of PCD followed by an immediate endoscopic transluminal procedure in the treatment of necrotizing pancreatitis, and showed improved clinical results and a decreased need for surgical intervention36,37. For our patients, the CNPI was maintained until all endoscopic procedures were complete. Only patient 6 experienced additional small-caliber PCD on day 3 after the endoscopic procedures because pelvic effusion was found on reexamined abdominal CT images.