From Step-Up to Step-Jump: A New Approach to Treating Infected Necrotizing Pancreatitis

1. Insights and Reflections on the “Step-Up” Treatment Strategy

The “step-up” strategy is based on the PANTER trial published by the Dutch Pancreatitis Study Group in 2010 in the New England Journal of Medicine. The results showed that there was no difference in mortality between the “step-up” and open surgery, but the rates of organ failure, diabetes, and incisional hernia were lower. Subsequent long-term follow-up of 73 patients over 86 months confirmed these results. The PANTER trial is regarded as a milestone event in the treatment of INP and has received widespread attention, making the minimally invasive “step-up” strategy one of the important methods for treating INP today. Recently, some scholars have pointed out design limitations in the PANTER trial: (1) The study did not stratify enrolled patients based on the characteristics of the necrotic tissue. It is generally believed that liquefied necrotic tissue is referred to as “wet” necrosis, primarily treated with drainage, while solid necrotic tissue is referred to as “dry” necrosis, usually treated with debridement. About one-third of patients in the “step-up” group were cured only through percutaneous catheter drainage (PCD), indicating that this group likely had predominantly “wet” necrosis, while a significant number of “wet” necrosis patients in the control group underwent direct open surgery, violating the aforementioned treatment principles. (2) The volume and quality of surgery performed by the surgical team are closely related, but the study did not specify the surgical volume of the surgeons performing open debridement, especially pancreatic debridement. (3) An encouraging result in the PANTER trial was that compared to the open surgery group, the “step-up” group also improved pancreatic exocrine and endocrine functions. It is well known that pancreatic debridement and drainage essentially remove necrotic pancreatic tissue and pus from the body. However, how to explain this phenomenon remains puzzling. (4) The sample size of the study was relatively small, and further validation through large-sample, multi-center randomized controlled studies is needed.

2. Proposal of the “Step-Jump” Cross-Step Surgical Intervention Treatment Strategy

INP presents various conditions, so a single treatment strategy cannot be applied to all patients; targeted individualized treatment should be adopted based on the different circumstances of patients. Jiang Hongchi et al. proposed the “three no” principles for surgical intervention in SAP: no blanket approach, no single model, no instant results. For instance, Burek et al. reported a case where a patient following the “step-up” strategy ultimately died from severe sepsis, raising the question: Is the “step-up” strategy applicable in all cases? Garg et al. evaluated the “step-up” strategy, stating, “The same shoe does not fit all feet.” In a single-center study of 305 patients with necrotizing pancreatitis (NP), 193 patients underwent endoscopic debridement, and 7% still required open surgery to save them from intractable pancreatic necrosis or intestinal perforation. It is evident that for a large number of “dry” necrosis patients with bleeding, infection, sepsis, enteric fistula, obstruction, etc., surgical intervention is necessary, and these patients require an earlier surgical intervention through the “step-jump” cross-step surgical intervention treatment strategy.

Unlike previous approaches that involved extensive anatomical debridement through large incisions early in the disease, delayed intervention and minimally invasive open surgery have become a consensus among surgeons. This significantly increases the success rate of SAP treatment. Delayed surgery has a time window to identify whether necrotic tissue is infected and whether surgical intervention is required, avoiding early surgery that can lead to unclear differentiation between necrotic and normal tissues, incomplete debridement, and potential damage to normal pancreatic tissue, blood vessels, and other organs, resulting in life-threatening complications such as massive bleeding and enteric fistula. Open surgery invariably converts sterile necrosis to infected necrosis. Research from Massachusetts General Hospital shows that the mortality rate for patients undergoing open debridement within 4 weeks of onset is 20.3%, while the mortality rate for those undergoing debridement after 4 weeks is only 5.1%. A study in Finland indicates that if surgery is delayed until 4 weeks after onset, the mortality rate for open surgery is 10.6%. The Liverpool Pancreas Centre observed significant improvements in mortality and overall complications among patients undergoing open debridement when comparing data from 2008-2013 with those from 1997-2007. Additionally, patients undergoing open debridement often have more severe conditions and frequently present with extensive retroperitoneal necrosis.

Compared to other methods, open surgery may not necessarily lead to increased mortality. In the PANTER trial, there was no significant difference in mortality between the open surgery group and the “step-up” group. Recently, a Japanese multicenter retrospective cohort study found no significant difference in mortality between open surgery and endoscopic, PCD, or video-assisted retroperitoneal necrosectomy (VARD) for treating IPN, although more patients received the latter treatments. The authors suggested that open surgery is also a reasonable choice. Cao et al. reported that for multiple referred INP patients, performing “one-step” surgical debridement without prior PCD did not increase mortality or complication rates but rather reduced hospital stay and number of surgical interventions. Surgical intervention does not necessarily have to undergo the “step-up” strategy’s second step of minimally invasive debridement. Wang Chunyou reported that their center has conducted various minimally invasive pancreatic debridement surgeries since 2011, and compared to solely performing PCD and open surgery before 2011, there was no statistically significant difference in complication and mortality rates, while the average number of surgeries per patient significantly increased. In fact, open debridement can provide thorough debridement in a single operation, especially beneficial in extensive necrotic lesions. Of course, some of the above studies included patients who were referred, whose necrotic infections were usually more severe, and some patients had already undergone interventions like PCD before admission. The author’s center has preliminarily established a scoring system for direct surgical intervention in INP, which is still being clinically validated. By assessing and selecting patients who inevitably require surgical intervention, they can benefit from prioritized surgical intervention strategies. Precisely selecting suitable patients for “step-jump” decisive surgical intervention will be an important topic for the future.

3. The “Step-Jump” Intervention Pathway: Choosing Between Percutaneous (Surgical) or Endoscopic (Oral)

Minimally invasive treatment is the trend in NP treatment; the measure of whether a method is minimally invasive should not be based solely on whether there is a skin incision, but rather on the total amount of trauma caused by different intervention methods. Due to the current lack of objective measures for assessing the degree of trauma, “minimally invasive” is sometimes a relatively vague concept, and the “pathway” of intervention seems to have become the only evaluation criterion for minimally invasive methods. Two small-sample randomized controlled studies and meta-analyses indicate that compared to surgical intervention, endoscopy does not reduce mortality but lowers complication rates. It seems that INP debridement should shift from percutaneous “serosal surgery” to endoscopic “mucosal surgery.” However, the aforementioned studies have significant design flaws. In the Bang study, only 28% of patients in the surgical group underwent PCD before surgical debridement, while the rest underwent direct debridement. In contrast, as high as 97% of patients in the endoscopic group had previously undergone endoscopic drainage and then turned to endoscopic debridement after symptoms did not improve. Furthermore, some patients in the endoscopic group actually received multimodal treatment; 41.2% had undergone PCD before endoscopic intervention. In the aforementioned meta-analysis, some important covariates (such as the location of necrotic tissue) were not considered. Endoscopic treatment is only suitable for lesions near the stomach or duodenum, while a significant proportion of pancreatic necrosis extends to the perirenal space and colonic gutters, which often require percutaneous intervention. Endoscopic treatment also has other drawbacks: the technical requirements for debridement are high, and it can currently only be performed in large medical institutions with experienced operators; it has not become widespread; from an economic perspective, endoscopic treatment is more expensive than surgical treatment, with longer course and requiring multiple interventions, which many patients may find difficult to afford; debridement efficiency is low, with discomfort from oral access, high bleeding risk, and difficulty in hemostasis, greatly exhausting patients’ mental and physical strength, and potentially delaying surgical timing; the treatment process is far from standardized, with differences in stent selection and placement times. As the meta-analysis concluded, the quality, heterogeneity, and low sample size of the included studies jointly determine the limitations of the trial results. Carr pointed out that in some comparative studies of endoscopic and surgical interventions, the authors attempted to compare the best endoscopic techniques with the worst techniques in open surgery. Boxhoorn et al. argued that due to the complexity and specificity of NP, it is extremely unfair to compare the superiority of surgical intervention versus endoscopic treatment at the current level of trial design. Gupta noted that both surgical and endoscopic methods are important treatment modalities, and direct comparisons can only be made in strictly matched cases. Given the current limitations of randomized study designs, more evidence is still needed to evaluate the advantages and disadvantages of different intervention methods.

In large pancreatic centers, percutaneous intervention techniques such as minimally invasive retroperitoneal pancreatic necrosectomy (MARPN), VARD, and even open pancreatic debridement can be performed safely and effectively. For appropriately selected patients, this will be a “first-line” treatment strategy. MARPN has advantages such as minimal trauma and minimal interference with abdominal organs. However, its surgical field is relatively small, and the operating space is limited, resulting in relatively low debridement efficiency, significantly impacted by the angle of the nephroscope and instrument limitations, and is usually suitable for necrotic tissue located in the head and tail of the pancreas, typically requiring more than three debridements to achieve optimal results. VARD is similar to the former, but due to limited exposure and suboptimal instrument operating space, debridement can sometimes be difficult and imprecise, requiring multiple debridements, with a higher risk of complications such as bleeding and enteric fistula. Case reports suggest that improved single-incision laparoscopic techniques may offer potential advantages in visualization and surgical space, allowing for more effective and safer debridement of necrotic tissue, possibly making it a better minimally invasive treatment than VARD.

Based on the author’s experience, a “step-jump” cross-step treatment strategy based on minimally invasive “three-incision” debridement has been proposed. A brief introduction is as follows: First, based on the established clinical predictive model for NP surgical intervention, it is determined whether to proceed with the “step-jump” cross-step surgical direct intervention. If “step-jump” treatment is adopted, small incisions in the upper abdomen and/or two small incisions in the retroperitoneum will be used for debridement (approximately 3-5 cm small incisions made in the upper abdomen or flank). For necrosis located in the peritoneal cavity or omental sac (“central-type” necrosis), debridement will be performed through the small incision in the upper abdomen; for infectious foci located in the bilateral retroperitoneal space (“bilateral-type” necrosis), debridement will be performed through the retroperitoneal small incision; for necrosis accumulating in both areas (“mixed-type” necrosis), a minimally invasive “three-incision” debridement combining both upper abdominal and retroperitoneal small incisions will be performed. During the treatment process, discussions with the multidisciplinary team (MDT) will be conducted as needed to implement multimodal surgical interventions or even expand the incision to convert to conventional open surgery. The minimally invasive “three-incision” debridement represents a new concept, proposing precise classification of pancreatic necrosis based on the characteristics of necrotic material (“dry” or “wet”) and location (“central-type,” “bilateral-type,” or “mixed-type”) to apply accurate treatment methods, enhancing debridement efficiency while minimizing damage to intra-abdominal organs and blood vessels. It differs from traditional extensive debridement surgeries through large incisions, representing an update and development in surgical techniques and concepts, enriching the connotation of minimally invasive techniques. The author believes its potential advantages are: (1) Minimally invasive, with less damage. (2) The pathway is easier to directly approach necrotic tissue. (3) Combined with various instruments, it offers high and thorough debridement efficiency, facilitating continuous drainage, washing, and tube changes post-debridement. (4) High safety, tactile feedback, and direct visualization minimize iatrogenic injuries. (5) Easier hemostasis for patients with bleeding. (6) Additional surgeries such as stenting, cholecystectomy, and biliary drainage are easier to perform.

4. The “Step-Jump” Intervention Technology Platform – Highly Integrated MDT

Currently, most medical institutions treat NP through a multidisciplinary model, with patients distributed among different specialties, often treated by a single specialty, leading to the following shortcomings: (1) Lack of collaboration and standardization among disciplines often results in technical limitations, failing to provide patients with comprehensive and reasonable treatment. (2) Hinders mutual communication, learning of new knowledge, concepts, and technologies. (3) A one-sided pursuit of specialty interests may harm patients and the healthcare system. In this model, more treatment strategies depend on the technologies and tools relied upon rather than the patients themselves, and doctors may not trust techniques outside their expertise. The author believes the ultimate solution is a highly integrated MDT, which formulates scientific, reasonable, and standardized individualized treatment plans for patients, thereby improving prognosis. The MDT I belong to is a high-capacity pancreatic disease diagnosis and treatment center, with more than 1000 pancreatic surgeries performed annually. It is characterized by high efficiency, low cost, real-time 24/7 availability, and “full coverage” MDT. The operational model involves a collaborative team of surgeons, ICU doctors, endoscopists, and interventional radiologists within one center, constructing a minimally invasive intervention technology platform for INP that includes PCD, MARPN, endoscopic debridement, and small incision open debridement. In this “family-like” model, the advantages of the multidisciplinary integrated technology platform for INP are maximized, achieving patient-centered care, real-time discussions of cases, and selecting the most appropriate treatment plan based on actual conditions. A patient-centered highly integrated MDT/pancreatic center will provide strong support for the treatment of NP. Given that multimodal multidisciplinary intervention strategies represent an improved surgical treatment model, they can reduce the incidence of complications for patients. This multidisciplinary treatment within pancreatic disease centers may become an important model for NP treatment in the future.

In summary, the “step-up” model is one of the important treatment modalities for contemporary INP, benefiting some patients. However, the complexity and variability of INP dictate that treatment cannot uniformly apply the same method; rather, it requires targeted treatment strategies based on the specific circumstances of each patient. For certain patients who inevitably require surgical intervention, the traditional “step-up” sequential treatment regimen should be bypassed, and the “step-jump” cross-step treatment strategy should be adopted for earlier surgical intervention. Clinicians should classify patients based on their actual conditions to construct clinical predictive models for different intervention methods in INP, enabling more precise classification treatment. A highly integrated MDT overcomes the shortcomings and limitations of specialty treatment, and establishing a disease-centered multidisciplinary integrated technical platform will be the future direction for INP treatment.