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Endoscopic and Minimally Invasive Therapy for Complications of Pancreatitis
Acute pancreatitis (AP) and chronic pancreatitis (CP) are dynamic inflammatory conditions that can result in local complications necessitating invasive treatment. Although AP and CP were previously considered and managed as distinct clinical entities, advances in experimental pancreatitis models, improved clinical characterization, and discovery of genetic mutations have resulted in a better understanding of the natural history and pathophysiology of what is now recognized as a clinical continuum. Local and systemic complications of AP and CP develop from the intrapancreatic activation of zymogens resulting in an inflammatory cascade, tissue ischemia, and pancreatic fluid leak. AP is differentiated from CP by the resolution of symptoms, histologic improvement, and generally the maintenance of pancreatic endocrine and exocrine function. However, in a subset of patients with persistent pancreatic enzyme activation or recurrent AP, there can be progression to inflammation-induced, permanent structural damage that is diagnostic of CP.
Early medical management of acute exacerbations of AP and CP are generally supportive in nature, focusing on assessment of disease severity, aggressive hydration, and pain control. When complications such as inflammatory pancreatic fluid collections develop, however, interventional therapies are often required. In 2012, the revised Atlanta classifications ( Table 94.1 ) for inflammatory pancreatic and peripancreatic fluid collections were released to provide standardized definitions to differentiate these lesions. Inflammatory pancreatic fluid collections were divided into four types including acute pancreatic fluid collections (APFC), acute necrotic collections (ANC), pancreatic pseudocysts, and walled-off necrosis (WON). The new definitions and classifications of inflammatory pancreatic fluid collections as distinct entities are important to recognize as the natural history, risk of subsequent morbidity and mortality, and outcomes of minimally invasive therapies are varied. Furthermore, the majority of antecedent literature reporting the outcomes of management is based upon heterogeneous combinations of these inflammatory fluid collections. In addition to inflammatory pancreatic fluid collections and their risk of infection, local complications of AP include biliary/gastric/duodenal obstruction, splenic and portal vein thrombosis, gastrointestinal bleeding/pseudoaneurysm, and internal/external fistulization. Patients with CP remain at risk for similar complications, such as pseudocysts and biliary obstruction, in addition to chronic pain with pancreaticolithiasis or ductal strictures.
TABLE 94.1
2012 Revised Atlanta Classification Definitions and Morphologic Features of Acute Pancreatitis–Associated Inflammatory Pancreatic Fluid Collections
Modified from Banks PA, Bollen TL, Dervenis C, et al. Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus. Gut . 2013;62:102–111.
| Pancreatic Fluid Collection | Type of Pancreatitis | Time | Well-Defined Wall | Contains Solid Necrotic Debris | Radiographic Features * |
|---|---|---|---|---|---|
| Acute pancreatic fluid collection | Interstitial edematous | <4 weeks | No | No | Homogeneous collection with fluid density Confined by normal peripancreatic fascial planes No definable wall encapsulating the collection Adjacent to pancreas (no intrapancreatic extension) |
| Acute necrotic collection | Necrotizing | <4 weeks | No | Yes | Heterogeneous and nonliquid density of varying degrees in different locations (some appear homogeneous if early) No definable wall encapsulating the collection Intrapancreatic and/or extrapancreatic |
| Pseudocyst | Interstitial edematous | >4 weeks | Yes | No | Well circumscribed, usually round or oval Homogeneous fluid density No nonliquid component Well-defined wall, completely encapsulated |
| Walled-off necrosis | Necrotizing | >4 weeks | Yes | Yes | Heterogeneous with liquid and nonliquid density with varying degrees of loculations (some may appear homogeneous) Well-defined wall, completely encapsulated Intrapancreatic and/or extrapancreatic |
The endoscopic, minimally invasive surgical and radiologic procedures available to practitioners managing the complications of AP and CP have rapidly expanded and provide an alternative to traditional open surgical management strategies. In concert with the medical technology expansion, the revised Atlanta definitions for inflammatory pancreatic fluid collections have provided more homogeneous data on outcomes and clinical management strategies. Given the heterogeneity of pancreatic fluid collections, local technical expertise, and anatomic variation, management decisions should be individualized within the context of a multidisciplinary team composed of surgeons, radiologists, and gastroenterologists.
Local Complications of Acute Pancreatitis
AP is a common inflammatory condition accounting for over 200,000 hospital admissions annually in the United States and over $2 billion in annual health care costs. Mortality from acute interstitial edematous pancreatitis is 3% to 5% ; however when associated with sterile pancreatic necrosis, the mortality rate increases to 15% and with infected pancreatic necrosis (IPN) to 30% to 40%. The mortality from AP occurs in two phases—an early phase, usually secondary to a severe systemic inflammatory response with multiorgan failure to the primary insult and a second, late phase, secondary to local complications including infected pancreatic and peripancreatic necrosis. Despite these concerning statistics, the vast majority of patients with acute interstitial pancreatitis and preserved perfusion will resolve without complications. Approximately 15% to 20% of patients develop pancreatic and peripancreatic necrosis, but in these cases, ductal disruption is invariable and complications are more frequent and illness is protracted.
Acute Pancreatic Fluid and Acute Necrotic Collections
According to the revised Atlanta classification, acute pancreatic collections include APFC and ANC and are diagnosed less than 4 weeks from the presentation of AP. APFCs are predominantly fluid-filled collections that occur subsequent to an episode of acute interstitial pancreatitis with no radiologic evidence of parenchymal or peripancreatic necrosis. ANCs contain a mixture of fluid and solid necrotic debris and tissue secondary to documented pancreatic or peripancreatic necrosis. These collections often do not require any therapeutic intervention as they are generally sterile, lack a well-defined, mature wall, and self-resolve after a few weeks. However, if they become infected or symptomatic, therapy may need to be considered.
A better understanding of the natural history of these collections reveals that although APFCs may occur in approximately 40% to 60% of patients with acute interstitial pancreatitis, the vast majority, approximated to be 85% to 90%, undergo spontaneous, self-resolution within 7 to 10 days. The residual 10% to 15% that persist beyond 4 weeks progress to pancreatic pseudocysts and are at risk for complications, including intracystic hemorrhage, rupture, or infection. APFCs that are large (> 6 cm), persist more than 6 weeks, are associated with CP, contain multiple cystic lesions (~10% of patients), are located in the tail, or have a wall greater than 1 cm in size have been reported to have a decreased likelihood of spontaneous resolution and need to be monitored serially to assess the need for intervention.
Patients with ANCs often present with a heightened systemic inflammatory response, multiorgan failure, and admission to the intensive care unit (ICU), which can be confounding when assessing for infection. In the initial 2-week time period, ANCs are typically sterile and should be treated with aggressive medical management. Surgical débridement of ANCs in the early stages should be avoided unless infection is confirmed and until the necrotic material has liquefied as prior data on urgent open surgical débridement was associated with excessive morbidity and mortality. If the patient develops recurrent systemic symptoms, such as fever, new or worsening abdominal pain, rising leukocytosis, an infected ANC should be suspected. In these cases, antibiotics with adequate pancreatic penetration should be initiated in an attempt to allow time for the transition from ANC to WON defined by the development of a mature, well-defined wall. With this transition, the WON can undergo minimally invasive débridement with reduced risk of complications.
Infected Pancreatic Necrosis
The cornerstone of management of severe AP is supportive care, typically in the ICU, with more invasive treatments, such as surgical, percutaneous, or endoscopic débridement reserved for patients with IPN, which develops in 40% to 70% of patients with pancreatic necrosis. WON was defined by the 2012 revised Atlanta classification as “a mature, encapsulated collection of pancreatic and/or peripancreatic necrosis that has developed a well defined inflammatory wall.” WON typically develops as an evolution of an ANC 4 weeks after an episode of severe acute necrotizing pancreatitis. In 2014, Sarathi Patra et al. reported the natural history of fluid collections in severe AP and found that 41% of patients with ANCs have spontaneous resolution, whereas 49% progress to WON. If sterile, treatment for WON is usually conservative; however if IPN is suspected by the presence of gas in a pancreatic or peripancreatic fluid collection on computed tomography (CT) or failure to respond to maximal ICU support and confirmed by aspiration or drainage and culture of the collection, antibiotics and invasive therapy are warranted. If left untreated, IPN has a mortality rate that approaches 100%.
The historical standard approach for the treatment of IPN has been surgical débridement with the goal of removal of all infected tissues. The significant mortality (11% to 39%) and complication rates (34% to 95%) associated with open necrostectomy, including the development of pancreaticocutaneous and enterocutaneous fistulas, incisional hernias, and exocrine and endocrine pancreatic insufficiency, led to the development and implementation of less invasive techniques, such as endoscopic necrosectomy and percutaneous drainage. Standard of therapy for IPN has been a multimodality “step up approach,” consisting of percutaneous catheter drainage followed by surgical necrosectomy; however, advances in endoscopic techniques have resulted in an evolving paradigm shift. As a result, clinical guidelines, including the International Association of Pancreatology and the American Pancreatic Association evidence-based guidelines, endorse percutaneous catheter or endoscopic transmural drainage as the first step in the treatment, followed by either endoscopic or minimally invasive surgical necrosectomy. Management strategies can be difficult and therefore require a multidisciplinary assessment. Regardless of approach, because demarcation and organization of necrotic tissues require several weeks and surgical mortality is greater following early intervention, it is preferable to defer débridement of IPN for at least 4 weeks following the onset of severe necrotizing AP.
Endoscopic Necrosectomy
For patients with an organized WON located within close proximity (~1 cm) to the gastric or duodenal wall, endoscopic necrosectomy has emerged as a therapeutic alternative to surgery. The technique for endoscopic necrosectomy involves initial guidewire access to the necroma either via direct puncture (in the case of a luminal bulge) or through the use of endoscopic ultrasound (EUS)-guided needle puncture and subsequent wire guided access. Once access is secured, the tract is dilated using a graduated dilating catheter, needle knife sphincterotome, or cystotome, and subsequent dilation to 15 to 20 mm is performed using a balloon dilator to allow passage of an upper endoscope into the necroma. Débridement is then performed using a combination of endoscopic accessories. Preservation of the tract is achieved by the placement of stents into the cavity across the gastric or duodenal wall. A variety of stenting options are available, including two or more pigtail stents, biliary or esophageal fully covered self-expanding metal stents (FCSEMS) and as of 2013, a FCSEMS with double-walled flanges, known as the lumen-apposing metal stent (LAMS), which can be noncautery enhanced (non-CE) or cautery enhanced (CE) to allow for one-step puncture and stent deployment ( Fig. 94.1 ). LAMS foreshorten on deployment and have the benefit of keeping the necroma wall and luminal wall in close apposition, theoretically reducing the risk of migration, and being large enough diameter to allow upper endoscope passage. Tract maintenance allows for repeated access and débridement following the initial necrosectomy. Placement of a nasocystic drain may be required for continuous lavage; irrigation with hydrogen peroxide and multiport access, known as the multiple transluminal gateway technique, may be beneficial in select cases.
Endoscopic necrosectomy/treatment of WON with plastic double-pigtail stents was evaluated in two multicenter retrospective trials with reported clinical success rates of 80% and 91% after necrosectomy, and procedure-related morbidity rates of 26% and 14% respectively. There has been one randomized, comparator trial by the Dutch Pancreatitis Group (PENGUIN study) in which 20 patients were randomized to endoscopic transgastric necrosectomy with plastic stents and surgical necrosectomy via either minimally invasive video-assisted retroperitoneal débridement (VARD) or, if not feasible, open surgery. In patients with infected necrotizing pancreatitis, endoscopic necrosectomy reduced the inflammatory response, had a lower rate of complications, and prevented new-onset multiple organ failure.
In 2016, a retrospective, multicenter study was published that involved 17 United States institutions that used a fully covered LAMS for the endoscopic management of WON. In this largest series to date of 124 patients, technical success was 100% with LAMS and clinical success was achieved in 86.3% after 3 months of follow-up. The median number of endoscopic interventions was two, the overall stent migration rate was 5.6%, and the overall rate of stent patency was 94%. Early adverse events (<30 days) occurred in 14% of patients and late adverse events occurred in 7.2%. There was no procedure-related mortality, which was an initial concern after the original two endoscopic necrosectomy multicenter retrospective trials had patient deaths attributed directly to the procedure. This difference is multifactorial but likely related to the improved understanding of the importance of a well-formed wall, the development of LAMS, and the use of carbon dioxide insufflation as a standard of care. The results of a large, multicenter (13 European institutions) study using CE-LAMS for inflammatory pancreatic collections, including 52 cases of WON, was published in 2015. Technical success was achieved in 98.9% of patients, and clinical success was achieved in 92.5%. Adverse events were reported in 5.6% of patients. Further prospective, randomized studies are needed to confirm the safety and efficacy of non-CE and CE-LAMS in WON; however, initial data are promising with high clinical success rates and minimal adverse events.
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