Complicated pancreatitis

Acute peripancreatic fluid collections / pancreatic pseudocyst

• Nomenclature:
  • Acute peri-pancreatic fluid collection: extra-pancreatic fluid collection within first four weeks of onset of pancreatitis, with no associated necrosis
  • Pseudocyst: APPFC which persists for >4 weeks, although histologically they can be present sooner
• Pathogenesis
  • Contains essentially pure pancreatic juice, with some cytokines and fibroblasts
  • Some say that this implies a definite connection to the pancreatic ductal system, whether or not there is a demonstrable radiographic connection
  • Hypothesised that the activation of pancreatic enzymes causes ductal disruption in some cases, leading to leakage of pancreatic juice, which can represent a temporary ductal injury, a stricture, or complete disruption of the duct
  • There is a correlation between duct disruption and persistent of pseudocyst
  • Unknown why pseudocysts sometimes develop in chronic pancreatitis without a significant episode of acute pancreatitis
• Imaging:
  • On CT: homogenous, no defined capsule, confined by retroperitoneal fascial planes, no intra-pancreatic extension (if there is a capsule, think cystic neoplasm or pseudocyst)
  • Review ductal anatomy to give likelihood of resolution: (this can be done on MRI/MRCP, and secretin helps but probably not worth the added cost)
    • Type 1: normal duct
    • Type 2: stricture in main pancreatic duct
    • Type 3: complete obstruction of main pancreatic duct
    • Type 4: chronic pancreatitis
• Natural history:
  • Identified in 30-57% of AP episodes
  • Most resolve on their own within a week or so
  • 7% persist as pseudocyst beyond 10 days
• Treatment
  • Only aspirate if high suspicion of infection (gas within collection, acute decompensation, failure to improve after 10-14 days)
  • Try to avoid giving antibiotics until aspiration is done
  • Observation, and wait for it to either resolve or mature
  • Interventions prior to 4-6 weeks only considered 'in the rarest circumstances'

Pancreatic pseudocyst

• Pathophysiology
  • Collection of pancreatic fluid lined by collagen and granulation tissue, not epithelium
  • The surrounding fibrotic reaction typically requires 4-8 weeks to develop
• Presentation
  • Symptoms related to mass effect - abdo pain, early satiety, obstructive jaundice, weight loss, fever if infected, peritonitis from rupture
• Natural history:
  • Overall 5-15% risk - higher-risk in chronic pancreatitis
  • Most spontaneously resolve
    • High-risk for persistence if the initial collection was >4cm or multiple lesions
    • Likely to resolve if <4cm, located in the tail, and no evidence of duct obstruction
• Imaging:
  • Encapsulated homogenous fluid collections with a well-defined non-epithelialised fibrous wall, usually outside pancreas
  • Minimal or no necrosis
  • Clues that it is actually walled off necrosis, not a pseudocyst: very thick wall, interior filled with necrotic debris, structure is very rarely circular
• Diagnosis
  • FNA - high amylase, absence of mucin, low CEA
• Masqueraders of cysts: (keep these in mind especially when cyst appears mature early in pancreatitis course - especially since these pathologies can actually CAUSE pancreatitis in the first place)
  • Cystic pancreatic neoplasm e.g. IPMN - look for mural nodules, fluid aspirate will be high in CEA and mucicarmine stain will be positive
  • Duplication cyst
  • True pancreatic cyst
  • Pseudoaneurysm
  • Solid necrotic neoplasm
  • Lymphocoele
  • GB pathology
• Manage conservatively if minimal/no symptoms and no evidence of pseudoaneurysm
  • VAST MAJORITY OF PSEUDOCYSTS DON'T REQUIRE INTERVENTION
  • Repeat imaging every 3-6 months, or sooner if deteriorates/worsening symptoms (to exclude infection or massive increase in size)
  • ?Nasoenteric feeding
  • PPI
  • ?Octreotide (not commonly used)
• Using ductal anatomy to predict management:
  • In Cameron's, they advocate for
  • Type 1 - non-surgical
  • Type 2 - trial non-surgical, with definitive surgical drainage for treatment failiures
  • Type 3 - essentially only treatable with surgery - lateral pancreaticojejunostomy or distal pancreatectomy/splenectomy
  • Type 4 - address chronic pancreatitis and fixing the duct should fix the pseudocyst
• Drainage can be performed endoscopically with assistance of EUS
  • Indications for drainage:
    • Persistent abdominal pain
    • Fever or other signs of infection
    • Gastric outlet obstruction
    • Failure to thrive
    • Biliary obstruction caused by extrinsic compression
    • Non-resolving in some cases, if they are large
    • Diagnostic doubt
  • Classically, endoscopic drainage if mature collection >6cm in size or persists >6 weeks (rule of 6)
    • However this rule has been challenged recently
    • (pseudoaneurysm is an absolute contraindication)
    • Much prefer to wait 4-6 weeks before draining
    • One of the reasons is, considering such a big pseudocyst, consider whether it could be a masquerading cyst i.e. IPMN
  • Techniques
    • Traditionally EUS-guided cystgastrostomy using double-pigtail plastic stents
    • Now lumen-apposing metal stents used more frequently - better success rate (93% vs 86%) plus allows access to cavity for debridement. These stents should be removed within 4 weeks to reduce risk of complications.
    • Needs to be <1cm to stomach/duodenum
    • Trans-papillary drainage can be attempted if the cyst communicates with the main pancreatic duct
    • If there is a stricture associated, endoscopic dilatation and stenting is indicated
  • Percutaneous drainage is also an option, but not favoured any more due to risk of fistula - only with infected pseudocyst - endoscopic transluminal is better
• Complications associated with pseudocysts
  • Obstruction (intestinal, vascular, biliary)
  • Infection
  • Rupture (pancreatic ascites)
  • Haemorrhage
    • First-line is urgent angio-embolisation or stenting
  • Fistula formation with the intestine

Necrotising pancreatitis (acute necrotic collection)

• The presence of non-viable pancreatic parenchyma or peripancreatic fat, and can manifest as a focal area of diffuse involvement of the gland
• Epidemiology
  • ~20% of all acute pancreatitis
  • Found in most patients that die from pancreatitis
• Pathogenesis
  • Thought to occur simply when pancreatic parenchyma has suffered enough insult that it can't recover
  • No convincing evidence for any specific populations that are at risk, or why it only develops in some patients - but does happen more often in severe pancreatitis.
  • Can be more likely with suboptimal initial resuscitation of acute pancreatitis
• Imaging:
  • Contrast CT is best method - seen as areas of low attenuation (<40-50 HU, compared to normal parenchyma of 100-150 HU)
• Acute necrotic collection occurs only in the context of acute necrotising pancreatitis
  • Heterogenous, variable amounts of fluid and necrotic tissue. No encapsulation.
  • Sterile (2/3)
    • Conservative treatment i.e. no antibiotics (STEP-UP APPROACH)
    • Antibiotics as required, nutritional support, IV fluids
    • If signs of systemic toxicity, repeat CT-guided FNA in 5-7 days
    • Indications for intervention:
      • Persistent pain
      • Failure to improve clinically with conservative management
      • Symptomatic biliary/enteric obstruction
    • Delay intervention as much as possible until it is walled off
  • Infected (1/3)
    • Mostly bloodborne dissemination, but can also get infected from local contamination from procedures
    • Most often >10 days after onset
    • Higher risk with more necrosis - up to 46% if >70% of pancreas affected
    • Suspect if systemic deterioration in a patient with necrosis, with persistent fever, leucocytosis, tachycardia, ileus, organ disfunction and sepsis, especially if that deterioration occurs >7 days after onset
    • Mostly monomicrobial with gut-derived organisms such as gram-negative rods
    • Diagnosis - air within collection, positive growth from aspirate, or clinical suspicion based on overall progress (up to 42% of patients with 'persistent unwellness' will have infected necrosis)
    • Treat with antibiotics (eTG says tazocin OR cef+met), if no improvement, progress to necrosectomy (endoscopic or percutaneous). Antibiotics known to penetrate pancreatic necrosis - carbapenems, quinolones, metronidazole, and high-dose cephalosporins.
• Prognosis
  • Dependent on the amount of pancreas that's necrotic
  • When >50% of the pancreas is necrotic, mortality approaches 40%
• Treatment
  • Initially, same as for AP
  • Don't routinely perform FNA unless clinical suspicious for infection
  • Preferable to delay treatment if possible (patient is stable) until necrosis is walled-off at four week mark (discrete inflammatory rind, parenchymal demarcation, and liquefaction of collection are all helpful). Trying to debride the pancreas earlier, when it's more friable and inflamed, lead to a massive inflammatory response, and higher risk of fistulae and haemorrhage. Even if intervening for another reason e.g. ACS, better not to touch pancreas unless you have to.

Walled-off necrosis

• A mature, encapsulated collection of pancreatic and/or peripancreatic necrosis with a well-defined, enhancing inflammatory wall
• The sequelae of acute necrotic collections which occurs >4 weeks after onset of AP
  • Note that the Atlanta Classification says strictly 4 weeks before walled-off necrosis can occur, but histologically it can actually occur sooner
• Seen in ~15% of patients with severe acute pancreatitis
• Treatment
  • Overall approach:
    • Delay intervention as much as possible to allow development of walled-off necrosis
    • Step-up approach - better long-term endocrine and exocrine function along with mortality in step-up as opposed to open necrosectomy. Endoscopic drainage with large-bore stent and possible endoscopic debridement, with or without percutaneous drainage, can avoid an operation in most patients.
    • If endoscopic/percutaneous approach fails, minimally invasive operations will usually be the next step
    • 65% of cases need only a single necrosectomy
  • Indications for intervention:
    • Infected necrosis:
      • With clinical deterioration or ongoing organ failure for several weeks (still prefer walled-off - all attempts at stabilisation should be made until 4 weeks after onset before intervening)
    • Sterile necrosis:
      • Ongoing gastric outlet, intestinal, or biliary obstruction due to mass effect 4-8 weeks after onset of acute pancreatitis
      • Persistent symptoms >8 weeks after onset acute pancreatitis
      • Disconnected duct syndrome (full transection of the pancreatic duct) with persisting symptomatic collections with necrosis >8 weeks after onset of acute pancreatitis
  • Step-up approach:
    1. Percutaneous drainage (fails in 25-75% of patients)
       • Especially useful in liquefied collections
       • Goal is to temporise until patient is more stable for minimally-invasive debridement, but in some cases perc drainage alone is sufficient (in Cameron's they say decrease in collection size by >75%, 2 weeks after drainage, predicts success without further intervention)
       • Preferably access through retroperitoneal route, so the drain tract can be followed with retroperitoneoscopy later
    2. Minimally invasive surgical drainage (roughly equivalent procedures in terms of outcomes)
       1. Endoscopic necrosectomy
          • Collection must be located within 2cm of stomach or duodenum
          • EUS is often used to positively identify collection, otherwise can look for bulging into stomach
          • Place a pigtail or stent between stomach/duodenum and collection
          • Particularly useful technique in cases of disconnected duct syndrome, because the drain needs to be left in situ permanently (or surgery)
          • Can be done as dual approach along with percutaneous drain, allowing flushing down perc drain with fluid then draining internally
       2. Video-assisted retroperitoneoscopic debridement
          • Currently the preferred technique, ahead of laparoscopic transperitoneal approach
          • Initially, imaging-guided drains are placed through retroperitoneal route, and upsized gradually, allowing visualisation with laparoscope, rigid nephroscope or endoscope
          • Morbidity is 20-30%, and mortality 0-20%
    3. Open necrosectomy
       • Traditional approach, rare now
       • Goal is complete drainage and removal of all necrotic tissue
       • Morbidity 34-95%, mortality 6-25%
       • Avoid in first week, and delay for as long as possible
       • Technique
         • Open
           • Upper midline
           • Check bowel for ischaemia/infarction
           • Open gastrocolic ligament
           • Blunt dissection using finger, sucker +/- Ligasure/harmonic
           • Scoop out necrotic pancreatic tissue
           • Irrigate and haemostasis
           • Drains - 4
           • Generally close the abdomen, although laparostomy and relook can be considered in the most severe cases
         • Trans-gastric
           • Upper midline laparotomy (can also be done through retroperitoneal flank incision)
           • Anterior gastrotomy
           • Open posterior gastric wall over collection
           • Debride necrotic tissue manually, leave as much pancreatic tissue as possible
           • Create ostomy between the capsule of the necrosis, and the posterior gastric wall, using a running locked 3/0 suture
           • NGT placed within the WON cavity (?could also use AXIOS stent for this)
           • Anterior gastrotomy closed
       • Afterwards, three possible strategies:
         • Open packing with repeat debridements every 24-48 hours
         • Closed packing - planned staged relaparotomies every 48 hours with closure of abdomen in interim, + drains
         • Closed continuous lavage uses large double-lumen drains to continue large-volume irrigation after abdominal closure. This is probably the superior technique.
           • 50-200ml/hour, infused down two of the four drains, with others on suction
           • Continue until clear effluence

Other complications of necrosis: (85% of survivors develop at least 1 complication)

• Pancreatic endocrine insufficiency (36%)
  • Highest in acute severe pancreatitis, necrotising pancreatitis, and alcoholic pancreatitis
  • May sometimes be transient
• Pancreatic exocrine insufficiency
  • Faecal elastase-1 concentration or C-mixed triglyceride breath test can exclude this. Treat with creon.
• Symptomatic chronic pancreatitis (16%)
• Disconnected pancreatic duct syndrome (49%) - viable area in tail but substantial necrosis in the neck - will present as collection/fistula. Can often be drained endoscopic transluminally with a double-pigtail plastic stent then managed as an outpatient with gradual shortening/downsizing of drain.
  • Imaging
    • Big obstructions or injuries can be seen on CT, but MRCP (+/- secretin), ERCP or fluoro drain studies are more sensitive
• Splanchnic vein thrombosis (45%)
  • See below
• Pancreaticobiliary duct stricture (5%)
• Chronic pain (8%)
• Gastrointestinal fistula (8%) - caused by enzymatic digestion. Can be managed with perc drainage about 50% of the time.

Other complications of pancreatitis:

Pseudoaneurysm

• • Theorised to result from elastase damaging vessels, leading to pseudoaneurysms
  • Sudden onset pain, tachycardia and hypotension
  • Treat with angio-embolisation, and surgical ligation if unsuccessful
  • Mortality 28%-56%

Splanchnic venous thrombosis

• • Usually splenic vein, but can extend into portal system in severe cases
  • Splenomegaly, gastric varices, splenic vein occlusion
  • Most patients can be managed conservatively, although thrombolysis has been described
  • Anticoagulation for splanchnic vein thrombosis associated with pancreatitis has not been shown to improve recanalization rates compared to expectant management
  • Recurrent UGIB caused by venous HTN should be treated with splenectomy

Abdominal compartment syndrome

• • Tissue oedema from third spacing, ascites, ileus, and peripancreatic inflammation
  • Drain pancreatic ascites where possible percutaneously - can make a big difference
  • Manage as per standard protocol, see separate topic

Pancreatic pleural effusion

• • Ductal disruption
  • Confirm with thoracentesis - amylase levels >50,000 IU in the pleural fluid
  • More common after alcoholic pancreatitis
  • >70% have associated pseudocyst
  • Right side likely accumulates dorsally over portal vein, whereas left effusion would likely be from pancreatic tail.
  • Needs chest drainage, nutritional support, and administration of octreotide - 60% respond
  • If no response, may need sphincterotomy and stent placement

Pancreatic ascites

• • Complete disruption of the pancreatic duct
  • Suspect in patients with AP who develop significant distension, and have free intra-abdominal fluid
  • Treat with drainage and stenting across the duct disruption
  • If that fails, will need distal resection and closure of the proximal stump

Pancreatocutaneous fistula

• • Rare, but can occur after necrosectomy, especially if distal pancreatectomy is done
  • Treatment mostly conservative

Colon necrosis

• • Segmental necrosis of transverse colon can be caused by thrombosis of middle colic arterial branches involved with the peripancreatic necrosis
  • Should be resected with ends brought out as a colostomy when identified