Department of Surgery and Cancer, Hammersmith Hospital, Du Cane road, London, W12 0HS, UK
Academic Editor: Prashanth Rawla
Received: February 25, 2019 | Accepted: May 31, 2019 | Published: June 05, 2019
OBM Hepatology and Gastroenterology 2019, Volume 3, Issue 2, doi:10.21926/obm.hg.1902022
Recommended citation: Kawka M, Gall TMH, Jiao LR. Managing Acute Severe Necrotising Pancreatitis. OBM Hepatology and Gastroenterology 2019;3(2):14; doi:10.21926/obm.hg.1902022.
© 2019 by the authors. This is an open access article distributed under the conditions of the Creative Commons by Attribution License, which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is correctly cited.
Acute pancreatitis is a common abdominal emergency with varied aetiologies and a diverse clinical course. Gallstones and alcohol are the main and important causes of acute pancreatitis . Other important causes of AP include hypertriglyceridemia, Post-ERCP, medications, genetic causes and pancreatic duct injury [2,3,4,5,6]. Some rare causes of AP include biliary sludge and microlithiasis, hypercalcemia, infections, biliary obstruction, biliary cysts and idiopathic causes  [8,9,10]. Most of the cases follow a mild or a moderate progression but approximately a third can be classified as severe acute pancreatitis [11,12]. According to Revised Atlanta Classification severe acute pancreatitis can be defined as acute pancreatitis coexisting with persistent organ failure (>48h) and/or necrotic changes, pseudocysts or abscesses . Multiple criteria such as APACHE II modified Glasgow score, highest recorded level CRP level or BISAP are also commonly used as tools for severity assessment . Amongst patients with necrotic changes, a third develop infected necrosis, which further worsens prognosis, with survival estimated to be between 15-35% in this group . Clinical severity and state of necrotic changes largely affect the management strategy and the decision for surgical intervention compared with conservative management. Infected necrosis is associated with SIRS due to a cytokine storm and can transform into sepsis, ultimately leading to organ failure, which further complicates the management of patients . In order to confirm infected necrosis either fine-needle aspiration (FNA) resulting in positive bacterial culture or contrast-enhanced computerised tomography (CECT) showing gas collections should be performed [17,18]. Traditionally, confirmed infected necrosis combined with poor clinical state provides an indication for surgical intervention, however currently this notion is being challenged with conservative and minimally-invasive techniques emerging .
Historically, open necrosectomy was a surgical management option for necrotising pancreatitis, however, the standards of surgical treatment have changed in recent years, with open surgery giving way to less invasive management options. Currently, there is no consensus on the best approach for severe necrotising pancreatitis (SNP) and the choice is primarily based on the experience of the surgeons, availability of the equipment and preference of the centre [12,15,17,20]. Commonly employed methods include open necrosectomy, percutaneous drainage (PD), endoscopic transluminal necrosectomy (ETN) video-assisted retroperitoneal debridement (VARD) and other minimally-invasive surgical variants including percutaneous necrosectomy . These surgical options can be used in combinations in so-called ‘step-up’ approaches when a less invasive procedure (most often drainage) can be followed by a more invasive procedure (VARD, ETN or open necrosectomy) in case of no clinical improvement . The list of techniques is not exhaustive and multiple variations of the aforementioned techniques are employed, as various centres introduce modifications [21,23].
To date, there have been a few studies aiming to assess the efficacy and comparing the outcomes of those multiple surgical strategies, thus allowing to formulate clear management pathways in severe necrotising pancreatitis. Most of the evidence regarding the management of SNP comes from either case series or retrospective comparative analyses. A general paradigm shift towards less invasive approaches can be observed in recent years, however, there still is a lack of consistent evidence to substantiate it, as some outcomes reported in trials do not always converge. This review aims to present the main available surgical techniques and compare the current methods of severe necrotising pancreatitis management.
A literature search was conducted in PubMed database to find substantial studies related to severe necrotising pancreatitis surgical management from the last 10 years. For the purpose of analysis randomised controlled trials, meta-analysis, pooled analysis of case series and retrospective studies (with more than 50 patients), involving comparisons of surgical methods were taken into consideration. The main focus of this review was comparative studies, highlighting differences between 2 or more surgical techniques. The main studies and their outcomes are highlighted in Table 1. This review focuses on necrotic collections, which can be classified as either walled-off necrosis (WON) or acute necrotic collection (ANC) and does not discuss acute fluid collections (AFC), abscess and pseudocyst management.
3. Management Strategies for Severe Necrotising Pancreatitis (SNP)
3.1 General Management
General management of acute pancreatitis involves aggressive fluid resuscitation, nutritional support and pain management . Traditionally, antibiotics would be given as prophylaxis, however, multiple RTCs have proven, that there is no evidence supporting their use without confirmation of infected necrosis [25,26]. If sterile necrosis is diagnosed, a conservative management pathway was confirmed to produce fewer complications and be a safe and efficient alternative of management . Although, the absence of infection in necrotic collections does not exclude a severe clinical course (associated with persistent organ failure or rapid clinical deterioration) sterility of necrosis is not an absolute contraindication for surgery in the later phase of the disease . The timing of intervention is an important consideration, that was debated throughout the years, but a literature review suggested that early conservative management with interventions in the later stages provides the best outcomes for patients . Delay in the intervention (approx. 3-5 weeks) allows the necrotic tissue to become liquified and more defined (walled-off), which makes removal easier and more complete [15,30,31].
Table 1 Summary of main studies on management of SNP.
3.2 Outcomes and Complications
Most commonly in the studies either mortality and/or major postoperative complications constitute the primary outcome (often in form of a composite outcome). Common complications include pancreatic fistula, haemorrhage, sepsis, new onset organ failure and type 3c diabetes, as well as incisional hernias and infection of the wound [20,32,33,34,35,36]. Secondary outcomes include the length of hospital stay, length of ICU stay, number of interventions performed and the cost of overall patient management [32,33,34,35,36,37,38]. Some studies also include the number of reoperations, utilisation of healthcare recourses and readmissions as outcomes .
3.3 Open Necrosectomy
Traditionally open necrosectomy (or debridement) was indicated for the management of SNP. This technique involves a longitudinal midline abdominal incision that allows full access to the lesser sac in order for necrosis removal and lavage, as well as assessment of the abdominal cavity . The operative technique has four main variations that differ in wound management and the need for planned reoperations including: necrosectomy combined with open packing; planned staged relaparotomies with repeated lavage; closed continuous lavage of the lesser sac; and closed packing . The rationale behind this technique is to achieve maximal preservation of healthy pancreatic parenchyma combined with the removal of necrosis and debris due to a big operation field, thus good access to collection in all regions of the pancreas. However, since less-invasive techniques were introduced open necrosectomy has been replaced in many centres as the primary intervention. It was noted that this method generates multiple complications including the creation of pancreatic fistulas, gastric outlet obstruction syndrome and incisional hernia, all of which contribute to need of reoperations and therefore increase the length of hospital stay and healthcare utilisation [39,40,41]. Moreover, major abdominal surgery provides additional stress to severely unwell patients which is thought to be one of the reasons for high mortality rates in this patient group .
In recent years, this paradigm was challenged in multiple trials comparing open necrosectomy with novel, minimally-invasive methods. In a pooled retrospective analysis van Brunschot et al. have concluded that the use of minimally invasive techniques (ETN or VARD) results in lower mortality in all patients analysed but more importantly in very-high and high-risk patient groups after stratification . Moreover, an RCT by van Stantvoort showed lower rates of major complications and new onset organ failure, when step-up approaches were compared to open necrosectomy . Recently, a follow-up of said randomised clinical trial was conducted by Hollemans et al. and showed that long-term complication rates can be reduced by using step-up approach (compared to open necrosectomy), although no significant differences in medical costs and quality of life was found .
3.4 Percutaneous Drainage (PD)
Percutaneous catheter drainage was introduced as one of the first minimally-invasive options of SNP management options around 2000 [43). The procedure involved insertion of a catheter either via the retroperitoneal approach or via the anterior transabdominal route depending on the location and size of the necrosis [43). The drain can be inserted either using a free-hand technique or under US or CT guidance and multiple drains might be utilised to provide the optimal level of drainage (44). Nowadays, PD is often used as the primary option, preferred by clinicians due to its relative non-invasiveness. Drainage allows for clinical improvement of the patient and therefore contributes to the delay of possibly more invasive surgical procedure, which is desirable if the surgical debridement is planned . A variation of this technique is endoscopic drainage, which also can be used as a primary intervention or part of the step-up protocols .
PD in multiple studies has a success rate of 30-50% as a primary intervention [32,46]. Its failure is most commonly attributed to the inability of the catheter to remove solid debris, (preventing improvement of the clinical status of patient), as well as the size of necrotised tissue, heterogeneity of collection and MOF [31,44,47]. PD was shown to be an effective first intervention of the step-up protocols, reducing major postoperative complications . A study by Gluck et al. has also shown that a combination of both endoscopic and percutaneous drains has a potential to decrease the length of hospital stay . Woo et al. have compared endoscopic and percutaneous drainage and found that endoscopic drainage is associated with shorter post-procedure length of hospital stay, as well as higher rates of SIRS-related parameter normalisation, although with no significant difference in CRP levels and WCC normalisation . In 2015 study, Stahl et al. have suggested using a U-tube catheter aimed at reduction of drain obstruction, fistula formation, more effective flushing and reduction of resource utilisation; preliminary results showed potential of this variant of PD .
3.5 Videoscope-Assisted Retroperitoneal Approach (VARD)
This variant of necrosectomy utilises a retroperitoneal approach, through the left lumbar region to access the pancreas . The use of video-assistance allows for the incision size to be reduced, thus minimising the trauma of surgery. A small percutaneous route toward the necrotic collection is established, which is then dilated to allow for full lavage and debridement . A variation of VARD which is also used is Minimal Access Retroperitoneal Pancreatic Necrosectomy (MARPN); it does not utilise camera assistance but follows the same principle, as far as debridement is concerned [20,52]. Similar to ETN and VARD, the choice for this method is predominantly determined by the location of the necrotic collection . The efficacy of this technique is still relatively unexplored in major trials or retrospective analyses. Using a retroperitoneal approach allows for a clear pathway to the necrosis. VARD is quoted to be superior over open necrosectomy due to a reduced number of post- and intraoperative complications and generating smaller inflammatory response in the organism following the procedure [52,38]. The critics have noted that a retroperitoneal approach is suitable only for certain locations of necrotic changes within the pancreas and hence cannot be utilised universally .
When directly compared with open necrosectomy, Raraty et al., Tu et al. and Guo et al. in their retrospective studies all found VARD and other minimally invasive surgical techniques to be associated with lower major complications rates and reduced length of hospital stay [52,35,33]. Moreover, an RCT by van Santvoort et al. showed VARD compared to open necrosectomy in surgical step-up protocols, was associated with a reduction in new onset organ failure and mortality (although the study was underpowered for mortality analysis) .
3.6 Endoscopic Transluminal Necrosectomy (ETN)
ETN is a technique that involves necrosectomy using an endoscope that is introduced into the necrotic collection via either transgastric or transduodenal (depending on the location of the necrotic changes) approach. It alleviates the risks of either open or surgical intervention. A flexible endoscope is passed transorally and then transmurally to perform a puncture of either the stomach or duodenum wall, to gain access to the necrosis [54,55]. Usually multiple procedures are needed to achieve a full debridement using this approach [30,34]. This method has been compared to other necrosectomy techniques and has, similarly to VARD, allowed for a reduction of major complications when compared with open necrosectomy. Moreover, a small randomised controlled trial by Bakker et al. has associated ETN with reduced complication rates and lower levels of pro-inflammatory mediators (IL-6) when compared to VARD . This is further confirmed by the study by van Brunschot et al., in which ETN was compared to VARD as a part of a step-up protocol (PD±ETN or PD±VARD) and was associated with reduced mean hospital stay and reduced complication rates .
3.7 Step-up Approaches
Step-up protocols are the most recent idea in the development of management strategies for SNP and have been already included in several major guidelines [13,17,56]. Their main premise is to use a less invasive technique first (in most cases drainage) and follow it by a more invasive intervention only if needed (ETN, VARD). The efficacy of ‘step-up’ protocols was investigated in the PANTER study in 2010 and since then multiple step-up protocols were suggested and investigated . When compared with open necrosectomy, step-up reduces the length of hospital stay [20,37]. The reports on reduced mortality are variable but generally step-up performs better or non-inferiorly compared to open necrosectomy [20,32,37,38]. In his 2014 study, Bang et al. compared an endoscopic step-up procedure with an ‘algorithmic’ approach, which (based on certain patient criteria) assessed the most suitable intervention and found that the algorithmic approach outperformed standardised step-up protocols with a success rate of 91% to 60% .
This review presents an overview of evidence about the management of acute severe necrotising pancreatitis. There is no unified management strategy, as there is a lack of a reliable predictive tool for clinical progression of necrotising pancreatitis. The choice of intervention is based on the preference of the clinician, availability of equipment and preference of the institution. There is significant heterogeneity in the methodologies used within procedures, with the majority of the studies not specifying which subtype of a certain technique was used, which partially hinders the ability to objectively analyse the outcomes. Moreover, the management of SNP patients is limited to specialised tertiary centres, from where most of the research output comes, which might contribute to an overestimation of success rate, had the more complex method been applied by other surgical teams; some teams in their case reports achieve significantly higher complications and mortality rates when compared to more renounced centres . Multiple studies suggest that the trend of moving towards less invasive surgical methods is associated with lower rates of major complications and mortality rate. Having said that, most of the studies lack statistical power to showcase mortality reductions significantly. It is also worth noting that while the differences in mortality are not always substantial, multiple studies have shown that less invasive approaches reduce the length of hospital/ICU stay and hence the costs of patient management.
All of the minimally-invasive techniques (whether as primary interventions or within step-up protocols) present as therapeutically viable options. It should be noted, however, that in comparison to open necrosectomy, both ETN and VARD require a higher level of surgical experience and in selected cases might not allow the best access to the necrotic collection. A considerable fraction of the patients was escalated to open necrosectomy in several case series, which emphasises the importance of open necrosectomy in management, despite more novel approaches being available. In our opinion, the current state of evidence supports the development of more formalised step-up protocols and their utilisation to limit major post-surgical complications, but it is still unclear what predicting factor could be used to determine which group of patients will benefit with more radical and invasive procedures. While research proves PD, VARD and ETN, as well as percutaneous necrosectomy as being viable options, the choice between them still remains unsubstantiated by evidence.
One of the biggest limitations of performing analysis is the current state of evidence of surgical management of SNP. Firstly, due to use of variable criteria, pancreatitis can be classified as severe according to several different metrics, thus some studies only had a proportion of patients with severe cases and some patients in the milder stages (14). This problem is also potentiated by the retrospective character of most of the studies and the lack of severity data collection. Secondly, most of the data related to open necrosectomy is from the 1990s and early 2000s, which in light of improved standards of ICU care and changes in pancreatitis management has reduced validity of comparison. Finally, due to the low incidence of severe necrotising pancreatitis and management being confined to tertiary referral centres, it is hard to plan randomised controlled trials with big sample sizes; most of the evidence comes from retrospective analyses which have an in-built bias.
In conclusion, current surgical management of severe necrotising pancreatitis is dependent more on preference and expertise of the clinician than reliable evidence. In our opinion, more robust evidence base is needed in order to comprehensively assess efficacy of less-invasive management methods in reducing mortality and identify patient subgroups benefiting from particular interventions in order to establish formalised step-up protocols.
These authors contributed equally to this work.
The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. No writing assistance was utilized in the production of this manuscript.
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