Superior to surgical approaches or not: Endoscopic necrosectomy has often been compared with surgical approaches to answer whether it is superior to surgical techniques, but conclusions varied[6,9,83]. The first-step comparison has been conducted in minimally invasive interventions and surgical open necrosectomy, and the following results are generally accepted. That is, minimally invasive approaches have replaced surgical open necrosectomy due to their advantages in the rate of the composite end point of major complications. Moreover, minimally-invasive surgical and endoscopic necrosectomy demonstrated lower mortality than open necrosectomy in a pooled analysis of 1980 patients. However, Comparing endoscopic step-up procedures to direct surgical necrosectomy may also lead to a bias in favor of endoscopic treatment.
Next, the second step compares two minimally invasive interventions, including the endoscopic transluminal and surgical step-up approaches. Reductions in the major complications, hospitalization time, and medical costs have been observed in the endoscopic transluminal step-up group in the TENSION trial, a randomized controlled, parallel-group superiority multicenter trial by the Dutch Pancreatitis Study Group. Moreover, besides reduced major complications and therapeutic costs, increased life quality has also been revealed in the endoscopic transluminal approach when compared with minimally invasive surgery in INP patients. In contrast, other studies have found that although the rate of pancreatic fistulas and hospitalization time is lower in the endoscopic group, no superiority in reducing major complications or mortality has been noted in the endoscopic step-up approach (EUS-guided transluminal drainage followed by endoscopic necrosectomy if necessary) when comparing with the surgical step-up procedure (percutaneous catheter drainage followed by video-assisted retroperitoneal debridement if required). The reasons for the differences or even the contradictions of various studies may be related to the differences in the sample size, the INP lesions, the specific endoscopic procedures, and the experience and perioperative management in different medical centers. In general, minimally invasive necrosectomy is currently recommended, among which endoscopic necrosectomy may be a better first-step option. When it comes to a specific patient, it is necessary to consider all INP-related factors and the therapeutic experience of the local medical institution.
How to improve the efficiency: If endoscopic necrosectomy sessions can be effectively decreased, it will reduce the operation-related complications and costs, shorten the treatment process, and improve the overall experience. Therefore, it has always been a hot issue in INP treatment. Since the frequency of endoscopic necrosectomy is affected by the necrotic proportion in INP patients, assessing the necrosis proportion is the first problem. However, there is yet to be a unified assessment protocol. Based on the current literature, the following drugs, devices, and techniques may help reduce endoscopic debridements.
Irrigation of the INP cavity is a commonly used procedure in INP patients undergoing invasive intervention. A three-step structured approach (debridement, necrosis extraction, and irrigation) has been developed and demonstrated fewer interventions. Irrigation can be accomplished by a nasal catheter, a percutaneous catheter, or a combination. Although percutaneous drainage has been considered one primary treatment for INP and helps most patients reduce open debridement in some studies, about one in five patients gets worse and requires open surgical intervention. Furthermore, recent research has revealed that streptokinase irrigation through a percutaneous catheter helps reduce necrosectomy sessions and mortality in a step-up approach. Constant saline instillation via nasocystic catheter between each necrosectomy procedure has been reported effective for improving drainage and reducing debridement operations[88,89]. However, it still needs to be determined whether continuous or intermittent lavage is more suitable for the INP cavity. In the meantime, complications have also been noticed, including forced irrigation-caused perforation, subsequent organ failure, and death. Another study has introduced a vigorous irrigation technique to reduce mechanical debridement, and no mortalities or following surgical needs have been reported in these patients. However, the reported mean time of stent retrieval seems prolonged than the recommended. Moreover, aggressive lavage with large-volume warmed antibiotic solution has also been reported as an efficient alternative to saline irrigation, and reduced rates of adverse events and mortality have been noted in previous studies. In addition, cessation of PPIs, local infusion of antibiotics, maximal fragmentation of necrotic tissue, and disruption of internal septate structures during the first necrosectomy can also improve drainage and reduce debridements[91-93].
In several previous studies, hydrogen peroxide has proven effective and safe in reducing debridements, even making external irrigation unnecessary in selected IPN patients[82,94]. Hydrogen peroxide has the advantage of healing INP by stimulating granulation and fibrosis, and foams produced by hydrogen peroxide in contact with organic tissue help remove the attached necrotic debris. However, its operation time and treatment course to achieve equal clinical efficacy with routine debridement seem prolonged, and this technique's optimal procedure and concentration remain to be further studied. Another recent single-center randomized pilot study has revealed that streptokinase irrigation in complicated INP cases demonstrates a lesser post-irrigation hospital stay and a reduced trend for mortality and necrosectomy sessions, while H2O2 irrigation may cause more bleedings, in contrast.
Besides, the optimal interval between each endoscopic necrosectomy remains unsettled. One possible reason may be the lack of data from large-scale multicenter RCTs. The current recommendation is 6.23 ± 4.71 d (range, 3-21 d), which is also based on endoscopists' experience. Suppose the interval can be shortened, or even an endoscopic debridement is performed at the same time as the first drainage; in that case, it seems beneficial in shortening the overall treatment duration. Although studies have reported that simultaneous drainage and debridement in a small number of selected patients does not significantly increase the incidence of serious complications, most experts do not recommend such procedures.
Furthermore, endoscopic transluminal necrosectomy still lacks dedicated instruments. However, some innovations have emerged in recent years. A new grasping tool, the over-the-scope grasper (OTSG), has been reported to overcome the disadvantages of time-consuming endoscopic removals of necrotic debris. OTSG can be attached to any standard gastroscope. Additionally, a novel powered endoscopic debridement system has been developed to achieve simultaneous resection and removal of solid debris. In recent research of a prospective, multicenter, international device trial, this system has revealed fewer interventions and shorter hospital duration in INP patients. Thus, it seems to be a safe and effective dedicated instrument for WON. Another novel prototype of the waterjet necrosectomy device has also been designed and has already demonstrated effectiveness in fragmenting necrotic debris and avoiding trauma to healthy tissue in animal experiments. The above-mentioned two new devices are compatible with therapeutic endoscopes with at least a 3.2-mm and a 2.8-mm working channel, respectively[99,100].
Additionally, it seems lacking attractive to compare the advantages and disadvantages of traditional endoscopic necrosectomy devices, and related comparative trials of these devices barely exist. In all cases, any device or technique used in endoscopic procedures must balance necrosectomy's efficacy with safety.
Predicting and managing complications: Despite all the aforementioned advantages and the promising future of endoscopic interventions, various complications should be addressed. Moreover, the prediction and management of potential complications should also be emphasized.
Common complications of endoscopic interventions in INP include bleeding, infection, perforation, pneumoperitoneum, and stent migration[33,62,63,101]. Bleeding is a dangerous complication with serious, even deadly outcomes, and it can be classified into two types: Intraoperative and postoperative bleeding. Intraoperative bleeding may occur near the fistula or inside the pancreatic collection. Common causes of bleeding include mechanical injuries and ruptures of pseudoaneurysm, collateral vessels, or other intracavitary blood vessels[60,102,103]. Timely and effective endoscopic management of these mild bleedings may not require interventional radiology-guided coil embolization or emergency surgery. Still, sometimes severe bleeding leads to the unfortunate outcome of the patient's death[60,62,63]. To date, the occurrence of bleeding has been presumed to be related to the type, size, and location of pancreatic collections; the type, diameter, and length of stents; varied intracavitary components; the time and protocol of endoscopic interventions; the experience of endoscopists; and the general health condition of the patient[62,102]. A novel algorithm has already been proposed for systematically managing hemorrhage events, which needs to be proven and refined in further RCT.
Moreover, infection often occurs in patients with poor drainage or a significant amount of solid necrosis. Using LAMS with a larger diameter, improving drainage efficiency, cooperating with antibiotics, and timely endoscopic debridement will help to improve or avoid severe infection in these patients[17,18,31,56,79]. Another human research has also demonstrated reduced intraabdominal infection by mouthwash with chlorhexidine and suspension of PPI before operation. Stent migration needs to be paid enough attention to in patients using LAMS or SEMS. Endoscopic or imaging follow-up and timely removal of the stent will help reduce the occurrence of stent migration. For long-term stent retention events caused by loss of follow-up or other reasons, most can also be solved by endoscopic interventions. In addition, intraoperative perforation, pneumoperitoneum, and postoperative obstructive jaundice caused by stent compression could be reduced or timely treated to avoid fatal consequences in an experienced endoscopic center[16,105].
Furthermore, how to predict high-risk patients with these potential complications? Several predictors have been studied. A relatively small size (≤ 7 cm) and delayed removal of the stent (≥ 4 wk) have both been reported as effective predictors for delayed bleeding and buried stent syndrome. Identifying intracavitary vessels during endoscopic interventions could also predict intraoperative bleeding, and patients with more transfusion requirements before interventions may require earlier radiological interventions. Meanwhile, a predictive model for potential complications after LAMS deployment in INP patients has been reported. Higher risks for adverse events have already been identified in patients with preoperative evidence of PD disruption, abnormal vessels (perigastric varices and pseudoaneurysm), and requirements of percutaneous drainage or hybrid techniques. Another research has also found that a significantly higher level of intracavitary amylase may indicate a higher risk of recurrence in INP patients. In addition, long-term sequelae in patients undergoing endoscopic therapy include pancreatic endocrine insufficiency, exocrine insufficiency, and long-term opiate use. These long-term complications should not be overlooked. Previous research has revealed that patients with exocrine insufficiency may have a significantly poorer health-related quality of life. These above studies help evaluate the potential risks and predict the prognosis before endoscopic interventions in INP patients. Further research will promote the continuous development of endoscopic interventional technology based on patient safety.
A multi-disciplinary treatment strategy: Despite all the progress of endoscopic transluminal interventions, INP remains a challenging and fatal condition. Due to lacking standardized endoscopic treatment protocol and considerable variations in the treatment selections among various endoscopists and medical centers, the short-term and long-term results of INP patients are affected by many factors. The optimal strategy varies in patients, especially those with high risks of potential complications. Moreover, not all patients with INP can be completely cured through endoscopic transluminal interventions alone. Thus it needs a multi-disciplinary treatment strategy in the whole clinical management of INP. A multi-disciplinary team (MDT) consists of therapeutic endoscopists, gastroenterologists, anaesthesiologists, intensive care unit physicians, sonographers, interventional radiologists, and surgeons. MDT aims to determine individualized treatment options for every INP patient, reduce mortality, improve clinical outcomes, and improve the risk-benefit ratio throughout the clinical treatment process. A staged, multi-disciplinary, minimally invasive "step-up" approach has already been proposed as an optimal treatment strategy for patients with INP, especially those with severe and complicated conditions[110-112].