Summary of the Evidence
Most of the PFCs are asymptomatic and resolve spontaneously. Persistent PFCs may be
associated with persistent systematic inflammatory response, mass effect on adjacent
organs, or development of infection. Patients having infected pancreatic necrosis
present with fever, leukocytosis, persistent or new-onset organ failure, or nonimprovement
in clinical condition (GRADE 1B).
Remarks
PFCs are common in AP. Acute necrotic collections (ANCs) have been reported in >90%
patients with severe disease. Most of the acute PFCs in mild AP resolve spontaneously
without complications.[2] Progression to walled-off necrosis (WON) is seen in about half of patients with
ANCs. Most patients with PFCs are asymptomatic. Those with persistent PFCs may develop
refractory pain, clinical manifestations secondary to pressure on adjacent organs,
rupture into the gastrointestinal (GI) tract, vascular complications, or infection.
In patients with acute necrotizing pancreatitis (ANP), infected necrosis should be
suspected when there is a clinical deterioration of a previously stable patient or
when there is a new-onset organ failure.[2] The timing when the clinical worsening happens is important in guiding a differential
diagnosis.[2] In the early phase (<14 days), fever, leukocytosis, and organ dysfunction are mostly
due to systemic inflammatory response syndrome (SIRS). Infection of pancreatic necrosis
usually occurs after this period. Most patients with necrosis develop infection after
3 to 4 weeks of onset of pain. In patients with necrotic collection and development
of fever in the later phase of ANP, infected necrosis may be clinically suspected
(in the absence of air in the collection) after exclusion of pulmonary, urinary tract,
and intravenous access infections.[2]
Arterial complications present as hematemesis, melena, or hematochezia when bleeding
occurs into the lumen of GI tract. When the hemorrhage occurs into the cavity, patients
may present with hypotension, shock, abdominal pain, anemia (hemoglobin drop), and
bleeding in the drainage catheters. Venous complications are mostly asymptomatic (GRADE 1C).
Remarks
Vascular complications occur in approximately 25% cases with AP.[3] The vascular complications occurring could be arterial or venous. Arterial complications
include PSA, active extravasation, arteritis, and arterial fistula. Venous complications
include thrombosis of the splanchnic circulation with formation of collaterals. Arterial
complications, seen in 4 to 10% of cases, present with hemorrhage, either into the
lumen, when they present with hematemesis, melena, or hematochezia, or into the cavity,
when they present with hypotension, shock, abdominal pain, anemia (hemoglobin drop),
and bleeding in the drainage catheters.[4]
[5]
[6] Occasionally, the patients may be asymptomatic, and the PSA may be detected incidentally
on imaging done for other purposes. Venous thrombosis, seen in 16 to 18% cases of
necrotizing pancreatitis, is usually asymptomatic.[7]
[8]
[9]
[10] Some patients may present with abdominal distension due to ascites or hematemesis/melena
due to the development of gastric or esophageal varices.[10] Splenic infarcts which result from splenic vein thrombosis may manifest with left
hypochondriac pain.[11] Clinically, it is important to differentiate between arterial and venous hemorrhagic
complications as this determines the next line of investigation. Arterial hemorrhage
usually presents with significant hemoglobin drop (>1–2 g/dL), bright blood in the
drain, and shock.
The bowel complications present with diarrhea, GI bleed, or drainage of bilious fluid/fecal
matter in the catheters placed in the infected collections. Mass effect of large collections
may result in symptoms like jaundice, early satiety, vomiting (due to gastric outlet
obstruction), or abdominal pain. Disconnected pancreatic duct syndrome (DPDS) presents
with persistent pain abdomen, recurrent collection, or pancreatic fistula (GRADE 1C).
Remarks
Bowel perforation and GI fistulas occurs in 3 to 15% of the patients with AP usually
in the late phase of the illness.[12] These bowel complications are the results of enzymatic action on the bowel wall
and evolve from the stages of bowel inflammation, ischemia, and necrosis. Patients
present with diarrhea, GI bleed, and prolonged sepsis. In patients with percutaneous
catheters in place, there may be feculent drain output.[13] Mass effect of collections in the upper abdomen may cause biliary obstruction, gastric
outlet, or intestinal obstruction.[2] These symptoms depend on the strategic location of the collection. DPDS is an under-recognized
complication of AP.[2] It is reported in 30 to 50% of patients with necrotizing pancreatitis. DPDS results
complete transection of the pancreatic duct by pancreatic necrosis.[2] This most commonly occurs at the level of neck of pancreas. The immediate consequence
is the persistent leakage of pancreatic enzymes, manifesting as nonresolving collection,
pancreatic ascites, pancreaticopleural fistula, and external pancreatic fistula (EPF).[14] Long-term sequelae include changes of chronic pancreatitis (CP) and recurrent AP.[15]
Contrast-enhanced computed tomography (CT) scan is the investigation of choice for
evaluation of patients with suspected infected pancreatic necrosis. Presence of air
foci within the collection is diagnostic of infected pancreatic necrosis (GRADE 1A). Fine-needle aspiration (FNA) of the collection for diagnosis of infection is not
routinely indicated (GRADE 1C).
Remarks
Presence of gas in pancreatic or peripancreatic collection on CT is strongly suggestive
of infection.[16] However, gas is present in only half of the patients with infected necrosis. The
sensitivity and specificity of gas within a necrotic collection in the setting of
AP is 56 and 97%, respectively.[17] Percutaneous FNA of peripancreatic collections to detect bacteria is not routinely
indicated. The clinical features including persistent fever and elevated inflammatory
markers in the later phase of the illness with or without presence of gas on CT are
accurate predictors of infected necrosis in most of the patients. Although the sensitivity
of FNA in the detection of organism is 79%, false-negative results are encountered
in 12 to 25% of the patients and there is a risk of introduction of infection in a
sterile collection.[16] A reasonable indication of FNA for detection of infected necrosis in the current
scenario is a patient without clear clinical and imaging features of infection but
lack of clinical improvement for several weeks.[18] Biochemical markers including blood urea nitrogen, C-reactive protein (CRP), and
procalcitonin have been utilized in the prediction of infection in necrosis, however,
have limited utility.[19]
[20]
CT angiography (CTA) is the investigation of choice for detection of the cause of
bleeding. Upper GI endoscopy (UGIE) should be performed in patients with mild bleeding
or in patients in whom CTA is negative and there is no significant hemoglobin drop.
Digital subtraction angiography (DSA) is mainly utilized for definitive management
of arterial abnormality. However, in patients with strong clinical suspicion in whom
other tests are nondiagnostic, DSA may be performed for diagnosis as well as treatment
(GRADE 2C).
Remarks
All patients presenting with hemorrhagic complications should be investigated. The
most important laboratory investigations are blood hemoglobin and hematocrit level.
In patients with necrotizing pancreatitis, approximately 60% of acute hemorrhagic
complications are caused by rupture of PSA.[21] Of the remaining, approximately 20% is due to capillary, venous, or small vessel
hemorrhage. Based on whether the hemorrhage is from an arterial or venous source,
the next investigation is determined. If an arterial source is suspected, which is
often the case, CTA is the investigation of choice.[22]
[23]
[24] UGIE should be performed when the bleeding is not severe or when CTA is normal.[23] Further, if the patient continues to bleed despite normal CTA, DSA may be necessary
to detect any small source of hemorrhage. There should be a low threshold to perform
a CTA because of the high mortality (34–52%) associated with the rupture of PSA.[4] Endoscopic ultrasonography (EUS) may be helpful in cases where UGIE, CTA, and DSA
are normal and bleeding is persistent.[25] EUS may show small PSA in and around the pancreas, which is seen as a small anechoic
lesion, showing color and pulsatile flow on color Doppler imaging.
UGIE and colonoscopy allow direct visualization of bowel abnormality in relation to
pancreatic necrosis. Contrast-enhanced CT scan with oral and intravenous contrast
serves as an important adjunctive method for the diagnosis of bowel complication as
well as other intra-abdominal complications. Conventional or CT fistulogram or tubogram
may be necessary to confirm fistula with small bowel or colon. Magnetic resonance
imaging (MRI) and magnetic resonance cholangiopancreatography (MRCP) allow the evaluation
of ductal abnormalities in patients with suspected DPDS; however, endoscopic retrograde
pancreatography is required for confirmation of diagnosis in selected cases (GRADE 2C).
Remarks
Diagnosis of GI fistula is suggested on CT when there is extensive air in a necrotic
collection, direct extension of peripancreatic inflammatory changes into a segment
of GI tract, a defect in the wall of GI tract with adjacent inflammation or contrast
leakage into pancreatic collection from the bowel loop, or contrast opacification
of bowel loop via contrast injected through a catheter placed in a pancreatic collection.[13] Colonic perforation appears as discontinuity of the bowel wall, contrast leak into
the adjacent soft tissue, or pneumoperitoneum/localized air collection around the
splenic flexure.[12] Confirmation is possible by imaging (contrast studies like tubogram, fistulogram,
oral contrast study, or contrast enema) or endoscopy.[26] The diagnosis of DPDS requires a combination of noninvasive imaging findings and
pancreatography (MRCP or endoscopic retrograde cholangiopancreatography [ERCP]).[27] The features of DPDS on CT/MRI are intrapancreatic collection or necrosis involving
the entire thickness of the parenchyma and functioning upstream gland. In a study,
all patients who were confirmed to have DPDS, the intraparenchymal abnormality, involved
more than 2 cm of the parenchyma.[27]
Drainage is indicated in majority of patients with infected pancreatic necrosis, the
choice of drainage being minimally invasive methods like percutaneous drainage and/or
endoscopic drainage. Necrosectomy (minimally invasive surgical or endoscopic) is required
in patients not responding to drainage (GRADE 1A).
Remarks
Over the last several years, there has been a paradigm change in the approach to management
of infected pancreatic necrosis. The surgical necrosectomy is now increasingly being
replaced by a minimally invasive step-up approach which comprises an initial drainage
(percutaneous or endoscopic) followed by minimally invasive necrosectomy (endoscopic
or minimally invasive surgical).[2] The PANTER trial popularized the concept of step-up approach. In this multicenter
randomized control trial (RCT) comprising 88 patients with (suspected) infected necrotizing
pancreatitis, the step-up approach led to a reduction in major short-term complications
such as new-onset multiorgan failure as well as long-term complications such as endocrine
insufficiency.[28] If the drainage (endoscopic, or percutaneous, or both) fails, the options are endoscopic
or surgical necrosectomy. Multiple trials have confirmed the efficacy, safety, and
reduced cost of endoscopic necrosectomy.[29]
[30]
[31] Endoscopic necrosectomy may be performed as direct endoscopic necrosectomy following
EUS-guided transmuralcystogastrostomy (as a primary or secondary procedure) or through
the transcutaneous access after tract dilatation (percutaneous endoscopic necrosectomy).
Minimally invasive surgical procedures include minimally invasive retroperitoneal
pancreatic necrosectomy, video-assisted retroperitoneal debridement, and laparoscopic
debridement. A meta-analysis comprising eight studies found that infected necrosis
could be managed conservatively without surgical necrosectomy in 64% of the patients.[32]
Endovascular embolization is the treatment of choice in cases of arterial source of
bleeding. Endoscopic therapy should be performed wherever a source is identified on
UGIE. Transabdominal ultrasonography or EUS may be used to guide embolization in cases
the lesion is not identified on angiography and visualized on these modalities. Surgery
is reserved for patients who are hemodynamically unstable or where other therapies
have failed (GRADE 1C).
Remarks
DSA and endovascular embolization are the treatment of choice for patients with arterial
source of hemorrhage.[23]
[24] Performing a CTA prior to DSA in cases wherever possible is beneficial as it identifies
the causative artery, creates a roadmap for DSA, identifies any variations in the
arterial anatomy, and reduces the radiation dose and time of the embolization procedure.[33] Occasionally, DSA may not identify the source artery although the PSA is visualized
on CTA. In such cases, if the PSA could be seen on ultrasonography, percutaneous direct
injection of thrombin or N-butyl cyanoacrylate (NBCA) can be done to treat the PSA successfully.[22]
[33] Empirical embolization may be performed in cases where endoscopy localizes the bleeding
site and DSA does not show any abnormality. Usually gelfoam slurry is used for this
purpose. The endoscopic treatment options include clipping, sclerotherapy, and vasopressor
injection.[34]
[35] Clipping is a common treatment where a through-the-scope clip is applied on the
mucosal surface at the site of bleeding to seal it. Larger ulcers may require over-the-scope
clips. Venous bleeds due to varices are treated with sclerotherapy using glue injection
or with ligation of the varices. There are a few limitations of performing UGIE in
these patients. Patients are often sick and unstable and doing UGIE may not be safe.
Extensive hemorrhage in the stomach and duodenum may obscure the source of bleeding.
Further, in patients with hemobilia or hemosuccus pancreaticus, endoscopic treatment
is not possible. Another option is EUS-guided direct injection.[25]
[36] In cases where the PSA seen on CTA is not identified on DSA, EUS could be performed
to localize the PSA. Then, under the guidance of EUS, the PSA is punctured directly
and either thrombin or glue is injected. This should however be reserved for very
selective situations where the other methods have failed. Surgery is reserved for
unstable patients or when the endoscopic or radiological interventions fail.[23] The surgical procedures include ligation or repair of the causative artery, Whipple's
pancreatoduodenectomy, or oversewing the bleeding artery.
Gastroduodenal fistulas are managed conservatively. Fistulization at other sites of
small or large bowel requires bowel resection or surgical diversion in the form of
ileostomy with or without colectomy. Collections causing mass effect require drainage.
Chronic DPDS usually requires surgical treatment (GRADE 1C).
Remarks
In a series of 119 patients with AP and GI fistula, all duodenal fistulas were managed
successfully by nonsurgical management, while surgical management (in the form of
ileostomy or colostomy) was required for 61.1% of the colonic fistulae.[37] Rest of the patients with colonic fistulae were successfully managed by prolonged
percutaneous catheter drainage (PCD) or continuous negative pressure irrigation. In
another series of 52 patients with GI fistulae, 42 patients showed resolution after
PCD or control of infection.[38] Ten patients underwent ileostomy or colostomy. In a systemic review of colonic complications
of AP in 97 patients, Mohamed et al concluded that a trial of conservative management
may facilitate fistula closure in patients with stable disease.[39] Urgent surgery may be indicated in patients with bleeding secondary to GI involvement
or those with bowel perforation. For patients with stable clinical course who fail
trial of PCD and have contraindications to surgery, endoscopic treatment with over-the-scope
clips has been reported. The management of choice for chronic DPDS is surgical.[40] This involves resection of the upstream gland, with or without islet cell auto-transplantation.
If the upstream pancreatic duct is of adequate caliber, Roux-en-Y pancreatojejunostomy
may be performed.[41] The nonsurgical options include EUS-guided pancreaticogastrostomy and combined approach
utilizing PCD for internalization of pancreatocutaneous fistula followed by endoscopic
stenting.[42]
[43] In the early stage of DPDS, when the aim is to prevent recurrent collections, the
most widely used approach is to leave cystoenterostomy stents in place indefinitely
to maintain patency of the internal fistula and divert pancreatic secretions back
into the GI lumen.[44]
The vascular IR procedure used in the management of pancreatitis is mainly embolization
for hemorrhagic complications (GRADE 1C).
Remarks
As the majority of vascular complications in the setting of AP and CP are arterial
in origin, DSA and endovascular embolization are the mainstay of treatment.[23] Various endovascular embolization agents and techniques have been described. For
PSAs that are not accessible by endovascular route, percutaneous image-guided embolization
may be performed.[33]
The nonvascular IR procedures include PCD of PFC, upsizing of catheters, drainage
of ascites and pleural effusions, percutaneous biliary drainage, and percutaneous
cholecystostomy (GRADE 1C).
Remarks
PCD plays an important role in the management of patients with pancreatic collections
in the setting of AP. It is either done as a sole intervention or more commonly as
a part of multidisciplinary management strategy comprising endoscopic drainage and
minimally invasive necrosectomy.[28] The percutaneous catheters frequently need upsizing and revisions to maintain their
patency.[45] Percutaneous drainage of ascites and pleural effusion may be indicated on case to
case basis.[2] The biliary obstruction in patients with gallstone pancreatitis and less commonly
secondary to biliary stricture or extrinsic compression by PFCs is usually managed
endoscopically.[46] However, in rare situations where the ERCP fails or patient is clinically unstable,
percutaneous biliary drainage may be performed.[47] In patients with severe acute cholecystitis, percutaneous cholecystostomy may be
required if patient is deteriorating despite medical treatment.[48]
The most common indication of PCD is infected (suspected or confirmed) necrotic collection.
In the absence of infection, nonresolving organ failure for several weeks may be considered
for drainage, preferably at the stage of WON (GRADE 1C). Other less common indications of PCD are WON causing compressive symptoms, persistent
“unwellness,” intra-abdominal hypertension, or bowel complications (GRADE 2C).
Remarks
Sterile necrotic collections do not need drainage regardless of their size as most
resolve without intervention.[2] In a study by Manrai et al, 76 patients with WON who survived, 24 patients were
managed conservatively.[49] In another study by Rana et al, 30 (70%) of the 42 patients with WON did not develop
any complications during expectant management.[50] There was complete resolution of WON in 30% of the patients. Suspected or confirmed
infection in a necrotic collection is the most common indication for drainage. Although,
infection usually occurs later in the course of AP usually 3 to 4 weeks after the
onset in the WON, earlier infection may occur in one-fourth of the patients.[2] If the infected WON is adjacent to the stomach or duodenum, endoscopic drainage
is usually performed. However, majority of patients have deeper extensions of the
WON into the paracolic gutter and pelvis which requires PCD.[51]
[52] Additionally, drainage may be required for symptomatic ANC, particularly, in the
setting of infection.[2] In several recent series, PCD in the early phase of AP in patients with nonresolving
organ failure has been shown to have a beneficial role.[45]
[53]
[54] The compressive symptoms secondary to necrotic collections are rarely seen. In a
study of 639 patients with necrotizing pancreatitis, biliary obstruction or gastric
outlet obstruction necessitating intervention was reported in 1% of the patients.[55] Rare complications requiring PCD in the follow-up after sterile necrotizing pancreatitis
are pancreaticopleural fistula (in combination with endoscopic treatment), pancreatic
ascites, and symptomatic pseudocyst not amenable to endoscopic drainage.[2] Another cohort of patients with AP who may benefit from drainage of collections
is one with “persistent unwellness.”[2] These patients are reported to undergo drainage 6 to 8 weeks after onset of symptoms.
Invasive treatment of abdominal compartment syndrome is indicated in patients with
persistent elevated intra-abdominal pressure (IAP) above 25 mm Hg with new-onset organ
failure not responding to medical management and nasogastric and rectal decompression.[56] The World Society of Abdominal Compartment Syndrome recommends that PCD for abdominal
fluid should precede surgical decompression.[57] The later should be performed only when patients fail to respond to PCD.[58] As discussed in the sections above, PCD is also useful in the trial of conservative
management of GI fistulas.[37]
[38]
[39]
Endovascular embolization should be offered to all patients with arterial complications
associated with pancreatitis (GRADE 1C).
Remarks
Rupture of arterial PSA is associated with a high mortality.[4] All PSAs need treatment regardless of the size.[59] The preferred approach to manage the arterial complications is endovascular embolization
as it has established safety and efficacy.[33] CTA prior to DSA is useful as it allows the recognition of the involved arterial
territory and preprocedure planning of the embolization technique.
The relative contraindications to drainage of PFC and endovascular embolization of
arterial abnormalities are uncorrectable coagulopathy (international normalized ratio
[INR] > 1.5) and platelet count < 50,000/µL. Contrast allergy and deranged renal function
tests are the other relative contraindications for endovascular embolization. Lack
of bowel-free approach is an absolute contraindication for catheter drainage (GRADE 2C).
Remarks
The general contraindications for percutaneous and endovascular procedures also apply
to PCD and endovascular embolization in patients with complications secondary to pancreatitis.[60]Abnormally prolonged INR should be corrected with fresh frozen plasma to achieve
a value below 1.5. Platelet transfusion is required for patients with platelet counts < 50,000/µL.
Patients with documented allergy to an iodinated contrast agent needs to be carefully
assessed. These patients benefit from the change of contrast medium within the same
class and premedication.[61]
[62] Lack of a bowel-free (small bowel/large bowel) approach precludes PCD. In these
situations, surgery is often required. In contrast, transgastric PCD is safe.[63]
Drainage of infected PFCs should ideally be delayed (3–4 weeks after onset of pancreatitis).
Earlier drainage is indicated in patients with infected collections, large collections
causing pressure symptoms, intra-abdominal hypertension, or those with persistent
sepsis (GRADE 1C).
Sterile ANCs seldom require drainage and are managed conservatively.[2] Similarly, ANCs in patients with clinical deterioration, organ failure, and SIRS
with no features of infection are managed conservatively. Early interventions are
associated with a risk of bleeding and perforation of adjacent hollow viscera.[64]
[65]
[66] Infected ANCs, though less common, may require intervention early in the course
of the disease. Abdominal compartment syndrome, pressure symptoms caused by compression
on adjacent organs, and persistent sepsis are the other indications for early drainage.[56] The preferred method is PCD. Infected WON requires intervention. The current recommendation
to postpone interventions until 4 weeks is based on the experience with primary open
surgical necrosectomy.[55] As currently drainage is employed as the first intervention in the step-up approach,
delaying PCD until encapsulation might not be necessary. However, robust clinical
data are lacking in this context. van Grinsven et al did a systematic review of the
timing of catheter drainage in patients with infected necrotic collections.[67] Early catheter drainage of the symptomatic PFCs was shown to decrease IAP and interrupt
the inflammatory cascade. This has also been shown by a recent study.[68] A recent study by Mallick et al comprising 258 patients with ANC and 117 patients
with WON reported that early PCD is as efficient and safe as delayed PCD.[53] Another recent study by Mukund et al comprising 78 patients with ANC showed that
early drainage is associated with favorable outcomes.[54] The mean interval between symptom onset and PCD was 14.3 ± 2.4 days. More than half
of the patients were successfully managed with PCD alone. Postponed versus immediate
drainage of infected necrotizing pancreatitis (POINTER trial) is a RCT being undertaken
by the Dutch Pancreatitis group to investigate whether immediate catheter drainage
in infected necrotizing pancreatitis reduces the risk of complications as compared
with the current protocol of delaying intervention until the stage of WON.[69]
Percutaneous catheter placement may be performed under ultrasound or CT guidance based
on interventional radiologists' preference, and visibility and the location of collection
(GRADE 2C).
Remarks
PCD of pancreatic collections can be performed under ultrasound or CT guidance. Ultrasound
is easily available and allows real-time needle placement. Besides, ultrasound-guided
PCD may be performed even at the bedside in intensive care units. However, deeper
collections are not well visualized and may not be amenable to drainage under ultrasound
guidance. Deeper and retroperitoneal collections are better accessed with CT guidance.
With CT fluoroscopy, real-time placement of the needle is feasible. Fusion techniques,
including ultrasound/CT fusion achieve a higher technical success rate but may not
be suitable in patients with AP.[70] Upgradation of the catheter can be done under ultrasound, CT, or fluoroscopic guidance.
The feasibility of MRI-guided PCD of pancreatic collections has also been reported
but it is not required in most of the patients.[71]
There are no available data to support a particular size of initial drainage catheter;
however, expert consensus suggests that a large bore catheter should preferably be
used (GRADE 2C).
Remarks
Though there are no standard recommendations regarding the initial catheter size,
most of the expert pancreatologists agree that a larger bore catheter should be used.[55] The initial catheter size is based on interventional radiologists' preference. However,
a catheter size of 12 to 14 F is preferable. Following the initial PCD, upsizing of
the catheter is required in most cases. The final catheter size may be as large as
30 to 48 Fr depending on the response of the patient to initial drainage.[72] In a retrospective study by Bruennler et al there was no impact of initial catheter
size on the mortality of patients with infected pancreatic necrosis.[73] A recent study showed that large sized catheters are associated with better outcomes.[74] However, prospective randomized studies are required for better evidence.
The preferred route for drainage of pancreatic collections is retroperitoneal via
left posterolateral approach (GRADE 1C).
Remarks
The direct and the shortest path for drainage should be used. Vital organs should
be avoided. The route depends on the site, size, extent of the collection, and relationship
with adjacent organs. The various routes for drainage are retroperitoneal, transperitoneal,
transgastric, and transhepatic routes. The organs to be avoided are bowel loops, spleen,
and gallbladder. Retroperitoneal access via the left posterolateral approach is preferred
as the catheter can be placed along the long axis of the collection.[75] Additionally, this approach allows for minimally invasive surgical necrosectomy.
The transperitoneal route should be used when there is no safe window for retroperitoneal
drainage. The transgastric route for drainage of pancreatic collections is less commonly
employed.[76]
[77] However, in patients with ANC who are not candidates for retroperitoneal or transperitoneal,
drainage may benefit from transgastric drainage. In a recent study by Sugimoto et
al, transgastric PCD was performed in 54% of the patients. The transhepatic route
has been described for inaccessible lesser sac PFCs. In the published studies on the
transhepatic drainage of intra-abdominal abscesses and postoperative fluid collections,
100% technical success and no significant complications were reported.[78]
[79]
[80]
Catheter upsizing can be done in persistent collection with reduced output/clinical
nonimprovement/deterioration (GRADE 2C).
Remarks
Some authors advocate upsizing the PCD on demand, while others upsize it routinely.
The need for upsizing depends on various factors like size of the collection, extent
of necrotic debris and liquefaction, patient's response to drainage, and clinical
course. In a recent survey, two-thirds of the expert pancreatologists agreed that
upsizing of the PCD is useful.[55] The recent series on proactive catheter drainage have also shown that frequent catheter
upsizing improves the success rate of PCD and clinical outcomes.[45]
[60]
[81]
[82] Although there is a lack of conclusive evidence, catheter upsizing should be considered
in persistent collection with reduced output/clinical nonimprovement/deterioration.
Based on the available data, no single size limit may be recommended for catheter
upsizing (GRADE 2C).
Remarks
Despite a consensus regarding the utility of catheter upsizing, there are no data
to suggest a maximum size limit for percutaneous catheter. In a study on proactive
PCD, patients in the proactive group had a significantly larger final catheter size
(median, 16 F vs. 14 F). In the proactive group, 17 (42.5%) patients had a final catheter
size of 20 F or larger compared with only 6 (8.8%) patients in the standard group.[63] In another study, the final catheter size was 18 F.[81] The maximum size of catheter in the study by Gupta et al was 28 F.[82] The maximum size depends on the extent of necrotic debris within the collection
and the protocol for management. Percutaneously, up to 28 F catheters can be placed
for drainage, particularly for ANC with necrotic debris and when sinus tract endoscopic
necrosectomy is needed.
Although there is a consensus that percutaneous catheter should be irrigated with
saline, there are no clear recommendations regarding the frequency of irrigation and
amount of fluid (GRADE 2C).
Remarks
Percutaneous catheter is likely to be blocked by the necrotic debris. Irrigation of
the catheter is critical to maintain its patency. Additionally, instillation of saline
may be utilized for removal of necrotic debris proactively from the PFC. There is
a lack of data reporting the use of saline irrigation in these two different contexts.
In the PANTER trial, 50 mL of normal saline was instilled every 8 hours.[28] Observational studies reporting PCD of pancreatic collections have used volume of
saline ranging from 10–20 mL to 1 L.[45]
[63]
[81]
[82] A recent RCT compared outcomes in patients undergoing large volume lavage (2.5–3 L
NS over 24 hours) with those undergoing gravity-dependent drainage.[83] Lavage treatment protocol led to a reversal of organ failure in a greater number
of patients.
There are little data to support the routine use of local intracavitary antibiotics
(GRADE 2C).
Remarks
Studies have questioned the ability of intravenously administered antibiotics to penetrate
PFC. However, there are few studies addressing this issue, with a limited number of
patients, in the early phase of AP.[84]
[85]
[86] In a retrospective cohort comprising patients with infected (suspected) WON treated
with endoscopic transmural drainage and necrosectomy, 91 patients received concomitant
intravenous and local antibiotics.[87] Local antibiotics were added to the irrigation fluid depending on microbiological
findings. Among patients with bacterial infections (n = 81), neither systemic nor local antibiotics were associated with the eradication
of microorganisms between first and second culture. However, the use of local antibiotics
was associated with the eradication of microbes between the second and third culture.[87] In a study comprising 48 patients with infected pancreatic necrosis, 19 patients
responded to systematic antibiotics and did not require any invasive intervention.[88] Endoscopic drainage and local antibiotic instillation were performed in 20 patients.
Nine patients improved while a similar number underwent necrosectomy. Two patients
in this group died. Another study demonstrated the safety and efficacy of local antibiotic
instillation through the naso-cystic drain.[89] In this study, 58 patients received amphotericin B, vancomycin, or gentamycin based
on the results of initial culture sensitivity. No detectable blood levels of vancomycin
and gentamycin were found. In total, 81% of the cultures responded to one of the antibiotics.
Based on the available literature, routine instillation of agents to facilitate the
liquefaction and drainage of necrotic debris cannot be recommended (GRADE 2C).
Remarks
The use of hydrogen peroxide has been demonstrated to be beneficial in the endoscopic
series. In a study comprising 19 patients with WON, extended cystogastrostomy and
hydrogen peroxide irrigation was performed prior to endoscopic necrosectomy.[90] Technical success was achieved in all patients and clinical success was achieved
in 18 out of 19 patients. Bleeding occurred in one patient and was controlled after
epinephrine injection and placement of a covered stent. In another study comprising
64 patients, technical and clinical success was achieved in 100 and 90.6% of the patients,
respectively, after EUS drainage and instillation of hydrogen peroxide.[91] Life-threatening bleeding occurred in three patients. In a multicenter survey of
hydrogen peroxide in endoscopic necrosectomy, 35% of the respondents routinely used
hydrogen peroxide.[92] There is limited utilization of intracavitary streptokinase for pancreatic collections.
In a preliminary study, in vitro installation was found effective in achieving lysis
of the necrotic contents. In vivo instillation was performed in two patients not responding
to the step-up approach and being considered for surgery.[93]
The catheter should be removed once the collection has resolved, and the drain output
is less than 10 to 20 mL/day for at least 2 to 3 days and there is no residual collection
on imaging (GRADE 2C).
Remarks
The decision to remove the catheter and stop the drainage is multidisciplinary based
on clinical improvement (control of sepsis, resolution of fever, hemodynamic stability,
and relief of pressure symptoms), improvement of laboratory parameters (total leucocyte
counts, CRP, and procalcitonin levels), and radiological improvement (resolution of
collection) with drainage less than 20 mL/day at least for 2 or 3 consecutive days.[45]
The standard technique for endovascular embolization is “sandwich” technique that
involves embolization of the arteries proximal and distal to the PSA (GRADE 1C).
Remarks
The standard embolization method is sandwich technique, due to the extensive collateral
vessels in the mesenteric circulation.[33] In this technique, arterial segments distal and proximal to the neck of the PA should
be occluded, thereby excluding the PSA from the circulation. This is typically done
by using coils. If access to the distal segment is not possible, other agents like
NBCA glue can be used.[94] Other embolic agents used include thrombin, gelfoam, and vascular plugs.[33] Uncommonly, when the PSA arises from a proximal segment of hepatic or splenic artery,
stent graft may be used to exclude the PSA.
The preferred embolization agent is coil (GRADE 1C).
Remarks
The most commonly used embolic material for pancreatitis-related arterial complications
are microcoils.[95] Once inside the vessel, the coils attain their inherent spring-like shape and cause
occlusion of the artery due to their thrombogenicity. In cases where the parent artery
needs to be preserved, the PSA sac may be carefully filled with coils or excluded
by a stent graft. For a wide neck aneurysm in a critical artery, one may use either
a covered stent or an uncovered stent with coils within the PSA for adequate occlusion.[33] Liquid embolic materials such as NBCA, glue, and ethylene vinyl alcohol copolymer
[Onyx; ev3, Plymouth, Minnesota, United States] provide effective permanent embolization
when the feeding artery or the PSA can be entered but not crossed to achieve proximal
and distal occlusion with coils.[96] Onyx is a liquid-embolizing agent primarily used in neuro-interventions such as
cerebral arteriovenous malformation and dural arteriovenous fistula embolization.
It has been used in few studies for GI embolization with good results.[97]
[98] Onyx has the advantages of being nonadhesive as well as having high radiopacity
and longer solidification time.[96] However, the disadvantages are increased cost and vasospasm. The use of onyx in
treatment of PSA has been described as a few case reports. In a series by Zabicki
et al comprising 15 patients, onyx was successfully used in two patients.[99] Gelfoam can be used as a slurry to cause temporary embolization of tortuous vessels
where the anatomy does not allow selective placement of a microcatheter. But its use
carries the risk of causing tissue ischemia because of distal vessel blockage. The
use of gelfoam alone has been described in a limited number of patients in published
series on the endovascular embolization of PSA.[100]
[101] Kulkarni et al reported gelfoam embolization in one patient in a series of 38 patients.
In the same series, gelfoam was used in combination with coils in two patients.[100] The only series describing the use of gelfoam with or without coils in all patients
comprised of 22 patients (27 bleeding sites).[99] The use of stent-grafts in PSA may be considered if it is involving the common hepatic
artery or its main branches which need to be preserved. Kulkarni et al reported use
of stent graft in one patient with a large PSA arising from the superior mesenteric
artery (SMA).[100]
Based on the limited data, embolization of PSA should be done prior to drainage (GRADE 2C).
Remarks
The data regarding the management of PFC in the setting of PSA are scarce. In a study
by Rana et al, eight patients (seven with AP and one with CP; six WON and two pancreatic
pseudocysts) with PSA were managed initially with endovascular embolization followed
by transmural drainage of the PFC.[102] All patients were managed successfully without any complications. The same group
also described successful management of pancreatic pseudocyst in the setting of PSAs
using angioembolization or percutaneous thrombin injection followed by transpapillary
drainage in eight patients.[103]
In a larger series, 58 patients with PSA with PFC developing as a complication of
AP or CP after discharge from the hospital were evaluated.[104] A combination of angioembolization and endotherapy resulted in a successful management
in majority of the patients. Only three patients required surgery. There were no major
complications, and 30-day mortality was low. In this study, there was 2-week interval
between embolization and endotherapy. This study comprised only pancreatic pseudocysts.
There is a limited role for percutaneous embolization of PSA in situations where the
endovascular embolization has failed or is not feasible and EUS-guided intervention
is not available or is not feasible or has failed (GRADE 2C).
Remarks
There are only a few case reports describing percutaneous embolization of PSA in the
setting of pancreatitis.[105]
[106]
[107]
[108]
[109] This mode of embolization has been utilized for cases with failed endovascular embolization
and the PSA is visible on USG. In a series of 19 patients with visceral artery PSAs,
percutaneous thrombin injection was used.[108] Seven pancreatitis-related PSAs were embolized using thrombin. There was failure
of aneurysmal occlusion in 5 (70%) patients. In another study reporting clinical profile
and outcomes in patients with pancreatitis-related PSA, out of the 46 patients, 9
patients underwent percutaneous thrombin injection. Reintervention due to recanalization
of PSA was required in only one patient.[109]
A significant proportion of patients with infected necrosis may be managed with PCD
alone (GRADE 1A).
Remarks
A systematic review of 384 patients from 10 retrospective studies and 1 RCT evaluated
the role of primary PCD for management of necrotizing pancreatitis.[110] Infected necrosis was confirmed in 70.6% of the patients. It was found that no additional
surgical necrosectomy was needed in 55.7% of patients. Mortality in the group of patients
with infected necrosis undergoing PCD was 15.4%. The recent series on pro-active PCD
have consistently shown a high success rate but the studies involve considerable heterogeneity
in terms of indications of drainage.[45]
[63]
[80]
[81] PCD is being increasingly utilized to stabilize critical patients. Once the patients
are stable, they may be considered for minimally invasive necrosectomy. These minimally
invasive interventions may be performed through the same tract. In another systematic
review, 15 studies comprising 577 patients were included. There was 1 RCT and 14 retrospective
case series. Definitive treatment was achieved in 56.2% of patients with PCD alone.
Additional surgical interventions were performed in 38.5% of patients. The overall
mortality rate was 18%.[111]
Endovascular embolization has a high technical and clinical success (GRADE 1C).
Remarks
Endovascular embolization for PSAs due to pancreatitis has a success rate of 79 to
100% and rebleeding rates of 18 to 37%.[96]
[112]
[113]
[114]
[115]
[116] In recent studies with patients recruited after year 2000, the success rate of endovascular
embolization was 95 to 100%.[112]
[113]
[115] Recurrence of bleeding is an outcome that must be suspected if patient develops
deterioration of vital parameters after initial improvement.
The immediate procedure-related complications include bleeding and bowel injury. The
long-terms complications are internal and EPF (GRADE 1C).
Remarks
Although bleeding is a life-threatening complication, it is rare. It may be related
to vascular injury secondary to catheter insertion or vascular damage induced by pancreatic
enzymes in the course of severe ANP. A CTA is performed to investigate the cause of
bleed from the percutaneous catheter. Arterial PSA or active contrast extravasation
is managed effectively with endovascular embolization.[109] Fistulous communication with bowel loop can be iatrogenic. However, more commonly,
it is the result of inflammation/ischemia of the bowel wall resulting from the effect
of pancreatic secretion. The most common site for bowel fistulization is the colon.[13] Other common sites are stomach and duodenum. The fistulization with upper GI tract
may be managed conservatively while the colonic fistula requires surgical management.[37]
[38] However, recent literature suggests that some colonic fistulae may be managed conservatively.
Other methods described for the management of colonic fistulae are over the scope
clips and stents. Slippage of catheter requires reinsertion if there is residual collection
and patient is symptomatic. Catheter upsizing is frequently required to prevent/treat
this event. Blockade of catheter can be prevented by regular saline flushing. EPF
is defined as the drainage of clear pancreatic secretions of greater than 100 mL/day
beyond 3 weeks of catheter insertion.[117] A majority of EPFs can be managed conservatively. However, in the case of refractory
EPF, pancreatic stenting may be required, if possible. In a multicenter study, 35
patients with EPF underwent endoscopic transpapillary stenting (n = 19) or conservative management (n = 16). There was no significant difference in the rates of fistula closure (84 vs.
75%, p = 0.18). However, patients in the former group had shorter median time to closure
(71 vs. 120 days, p = 0.13).[118] In a systematic review, complications were reported in 21.2% of the patients undergoing
PCD.[32] Of all the complications, 51.5% of the complications were pancreatic fistulas. Significant
bleeding was reported in two patients only. Colonic perforation and catheter dislodgement
were reported in one patient each. Another systematic review reported a complication
rate of 25.1%.[111] Like the previous meta-analysis, most common complication was fistulas accounting
for 44.8% of the total complications.
The most significant complication related to endovascular embolization of PSA is non-target
embolization (GRADE 1C).
Remarks
The complications of endovascular embolization may be related to the technique including
the type of embolic agent used and to the underlying clinical status of the patients.
With improvement in hardware such as coil designs and deployment systems, super-selective
microcatheter profile, the rate of complications is quite low.[25] However, organ ischemia such as splenic and liver infarction is possible especially
with use of liquid-embolizing materials blocking intraparenchymal branches during
non-target embolization. Intestinal infarction is a dreaded complication during embolization
of a SMA branch. Other complications include vascular dissections, migration of coils
and stents, and rupture of PSA. In a study by Vander Mijnsbrugge et al comprising
34 patients treated with endovascular embolization, there were no major complications.[119] Minor complications occurred in 30% patients. The most common complication was partial
splenic infarction that occurred in 10.8% of the patients and led to no significant
change in the treatment. Postprocedure fever was the next most common complication
in 5.4% of the patients and resolved with antibiotics. In another series by Zhang
et al comprising 40 patients (AP 19, CP 12, and postpancreatectomy for pancreatic
cancer 9), complications were observed in three patients with AP who were treated
using NBCA.[120] This series did not evaluate the incidence of minor splenic infarctions. In a series
of 12 patients with CP undergoing endovascular embolization of PSA, complications
occurred in two patients.[116] One patient had reversible hepatic ischemia due to migration of coli placed in the
gastroduodenal artery to the right hepatic artery. The other patient had stent stenosis
of the stent graft placed in the common hepatic artery. Series on NBCA have also reported
relative safety of the procedure. In a series by Madhusudhan et al comprising 31 patients
(including 24 patients with pancreatitis), minor complications (due to non-target
embolization) occurred in two patients and major complication in the form of catheter
fracture occurred in one patient.[95] Series by Izaki et al (nine patients) and Won et al (13 patients) reported no major
complications. In both the series, minor complications occurred in two patients and
were related to non-target embolization.[121]
[122]
There are no data to suggest a follow-up protocol specifically for patients treated
with PCD. However, the follow-up evaluation of patients with AP includes a comprehensive
evaluation by a team comprising medical gastroenterologist, surgeon, and interventional
radiologist (GRADE 2C).
Remarks
Follow-up evaluation must address three important areas including the prevention strategies
based on etiology (cholecystectomy, abstinence from alcohol, management of hypertriglyceridemia,
hypercalcemia, etc.), assess the local complications (PFCs), and systemic complications
(diabetes mellitus, steatorrhea, and weight loss).[123] From the interventional radiologists' perspective, patients need to be evaluated
for the status of PFC. There is no recommended protocol for follow-up.
Following endovascular embolization, patients must be assessed clinically and by serial
evaluation of hemoglobin levels to confirm the clinical success. USG may be done to
follow up previously visible PSA. There is no clear recommendation for follow-up CTA
in patients with resolution of bleeding (GRADE 2C).
Remarks
There is no clear recommendation for imaging follow-up of patients treated endovascularly
for PSA. Although previous studies have reported the timing of recurrence of PSA,
these data may not be enough to suggest a protocol for follow-up imaging. In a long-term
follow-up study by Vander Mijnsbrugge et al (mean CT scan follow-up of 40.5 months
and clinical follow-up of 80 months), all recurrences (4/34) occurred within first
5 months.[119] However, three PSAs arose in different arteries and only one was a true recurrence.
In another series comprising six patients who underwent primary endovascular embolization,
rebleeding occurred in three patients at a mean interval of 61.3 days (range: 21–136
days).[122] In a series of 12 patients who underwent endovascular embolization, all patients
had an initial follow-up CT scan at a median of 8 days (range: 1–28 days) after the
embolization.[124] Resolution of PSA was documented in all. Eleven patients underwent another follow-up
using CT (n = 10) and Doppler (n = 1) and all had no recurrence of the PSA. The timing of this follow-up imaging was
not mentioned.[125] In another series comprising 40 patients who underwent endovascular embolization
of PSA in the setting of AP, CP, or pancreatic cancer following surgery, rebleeding
was encountered in eight patients. All patients had rebleeding at a mean interval
of 8 days (range: 0–15 days).[120]
