Читать книгу Clinical Pancreatology for Practising Gastroenterologists and Surgeons - Группа авторов - Страница 191

Historically, surgical debridement was the traditional management strategy for symptomatic necrosis with and without the presence of infection. This was done via an open approach with a wide drainage area and placement of multiple abdominal drains, usually with the need for repeat operative procedures over a prolonged period of time; reintervention rates from larger European and American series ranged from 30 to 70%, with associated morbidity and mortality estimated at 11–50% in some series [20–22]. In a series of 167 patients with necrotizing pancreatitis, 72% of whom had infected necrosis, surgical outcomes from a single‐step debridement and closed packing technique was evaluated and showed a 12.6% risk of reoperation, 29.9% rate of subsequent requirement for percutaneous interventional radiology drainage, and overall operative mortality rate of 11.4%. Additional complications included postoperative pancreatic fistulas (41%), enteric fistulas (15%), endocrine pancreatic insufficiency (16%), and exocrine insufficiency (20%), while 57% required prolonged admission to the intensive care unit [21]. Though necessary to surgically intervene at times, the substantial associated morbidity and mortality served as the foundation to seek other interventional avenues to improve the overall outcomes.

Beyond open surgical debridement, multiple additional therapeutic interventional options exist for the treatment and management of pancreatic necrosis. These options include endoscopic intervention, percutaneous intervention, and minimally invasive surgical approaches including video‐assisted retroperitoneal debridement (VARD). In the percutaneous approach, multiple large‐bore catheters are placed into the collections under imaging guidance and the cavities are regularly flushed to promote liquefaction and drainage. Percutaneous approaches are relatively safe, with low complications and mortality, and may be used to guide additional necrosectomy subsequently by providing an access tract, as well as allowing patients who would otherwise not be candidates to undergo endoscopic or minimally invasive surgical approaches. Because percutaneous approaches are primarily a flush and drain approach, as opposed to direct debridement, this may limit their efficacy. In systematic reviews, the efficacy of percutaneous drainage is estimated to be 44–55% in treating necrosis and avoiding the need for subsequent surgery, making percutaneous drainage an attractive potential option either as a bridge to other interventional options in an unfit procedural candidate or as destination therapy in approximately half of patients [23,24].

As new approaches continue to evolve, there is increasingly more evidence to substantiate the use of endoscopic necrosectomy, laparoscopic transperitoneal or video‐assisted retroperitoneal debridement, and percutaneous drainage. Cystgastrostomy with nasocystic irrigation for the treatment of WON was first reported in 1996, and transluminal direct endoscopic necrosectomy followed in 2000 [15,16]. Subsequently, there has been much work to further investigate the optimal management strategies and performance characteristics of each management strategy. Multiple initial studies demonstrated the efficacy of transgastric access into the retroperitoneum with debridement of necrotic tissue, followed by placement of stents into the collection to enable continued drainage [25–27]. The current standard of care when accessing these collections endoscopically is the use of EUS to confirm the location of the collection, characterize the collection, and ensure that there is no vascular structure in the interceding area between the puncture site and the collection [28].

Endoscopic transgastric necrosectomy was first compared to surgical necrosectomy in the randomized PENGUIN trial (Pancreatitis Endoscopic Transgastric vs. Primary Necrosectomy in Patients with Infected Necrosis) by Bakker et al. from the Dutch Pancreatitis Study Group, in which endoscopic necrosectomy led to a decreased proinflammatory response and was associated with a substantially reduced incidence of major complications or death (20% vs. 80%) [25]. In the PENGUIN trial, the endoscopic approach consisted of initial transgastric puncture followed by balloon dilation of the tract and subsequent drainage and necrosectomy, whereas the surgical approach first focused on VARD or laparoscopic debridement as opposed to open surgical necrosectomy if VARD was not possible. Subsequently, a step‐up management approach was proposed that primarily aims at control of any subsequent infection and aims for minimally invasive management strategies as opposed to open necrosectomy, with a stepwise progression from percutaneous to endoscopic to VARD or laparoscopic drainage and debridement. The step‐up approach was compared in the PANTER trial in which van Santvoort et al. [29] demonstrated a significant reduction in their primary composite end point of death or major complications in which this composite outcome was found in 40% of patients undergoing a minimally invasive step‐up approach compared to 69% of those undergoing primary open necrosectomy [relative risk (RR) 0.57, 95% confidence interval (CI) 0.38–0.87; P = 0.006]. Interestingly, in this initial study, laparoscopic necrosectomy was not part of the algorithm, and in the step‐up approach only a small proportion of patients underwent endoscopic necrosectomy whereas most underwent percutaneous drainage and then VARD.

These two large studies laid the foundation for hybrid management strategies in a multidisciplinary approach comprising gastroenterologists with therapeutic endoscopy training, interventional radiologists, and surgeons. No particular size fits all, and the combination of multiple strategies may achieve the best outcomes in these oftentimes complex and very ill patients. More recently, there have been several large randomized trials and meta‐analyses to investigate the nuances of the step‐up approach and its efficacy. Hollemans et al. [30] recently reevaluated the patients initially presented in the PANTER trial with regard to their long‐term outcomes and management; 73 of the initial 88 patients were still alive and able to be studied at a mean of 86 months post index admission, with a primary end point of death or major complications as well as long‐term development of exocrine pancreatic insufficiency, endocrine insufficiency, and quality of life and pain scores. From index admission to long‐term follow‐up, there was a significantly higher rate of death or major complications in the open necrosectomy group compared with the surgical step‐up approach group (73% vs. 44%; P = 0.05). Further, those undergoing open necrosectomy were more likely to have exocrine pancreatic insufficiency (56% vs. 29%; P = 0.03) and endocrine insufficiency (64% vs. 40%; P = 0.05), again demonstrating on a long‐term basis the superiority of a surgical step‐up approach compared to open necrosectomy.

Van Brunschot et al. [31] investigated EUS‐guided transluminal drainage with endoscopic necrosectomy versus a surgical step‐up approach in a multicenter randomized superiority trial involving 19 hospitals in the Netherlands. A total of 98 patients were enrolled and randomized, with no significant differences in mortality rates (18% in endoscopy vs. 13% in surgery), nor any significant differences in any other major complication, though there were lower rates of pancreatic fistula formation and length of stay in the endoscopy group. Bang et al. [32] conducted a single‐center randomized trial of 66 patients with confirmed or suspected infected pancreatic necrosis requiring intervention with randomization to minimally invasive surgery (either laparoscopic or VARD) or endoscopic step‐up approach including transluminal drainage with and without necrosectomy with a composite end point of major complications, including new‐onset multiorgan failure, new‐onset systemic dysfunction, enteral or pancreato‐cutaneous fistula, bleeding, perforation, or death. Of the patients undergoing the endoscopic approach, 11.8% reached the composite end point whereas 40.6% of patients undergoing surgical interventions reached the composite end point (RR 0.29, 95% CI 0.11–0.80; P = 0.007). There were no significant differences in mortality among groups but none of the patients undergoing endoscopic approaches developed fistula, while 28.1% of patients undergoing surgery developed fistulas (P = 0.001), with a significantly higher mean number of complications in the surgical group as well. The mean total cost was also significantly lower in the endoscopic group compared to the surgical group (US$75 830 vs. US$117 492; P = 0.039) [32]. Khan et al. [33] performed a meta‐analysis evaluating the safety of endoscopic drainage versus minimally invasive surgical necrosectomy in the treatment of WON, in which two randomized controlled trials and four observational studies of 641 patients were included, with an overall 8.5% mortality rate in the endoscopic drainage group compared with a 14.2% mortality rate in the minimally invasive surgical necrosectomy group, with a pooled odds ratio (OR) of 0.59 favoring endoscopic drainage (95% CI 0.35–0.98). Further, rates of development of new major organ failure post intervention were 12% in the endoscopic group compared to 54% in the surgical group, with a pooled OR of 0.12 (95% CI 0.06–0.31) favoring endoscopic drainage, a lower overall adverse events rate favoring endoscopic drainage (pooled OR 0.25, 95% CI 0.10–0.67), as well as shorter length of stay in the endoscopic group with a pooled mean difference of –21.07 days (95% CI –36.97 to –5.18 days).