PSEUDOCYSTS IN CHRONIC PANCREATITIS
Shailesh V Shrikhande, Helmut Friess, Markus W Buechler
Department of Visceral and Transplantation Surgery, University of Bern, Inselspital, Bern, Switzerland.
Pseudocysts of the pancreas are collections of pancreatic juice surrounded by a wall of fibrous tissue that is not lined by epithelium.  Pseudocysts are connected with the pancreatic duct system either as a direct communication or indirectly via the pancreatic parenchyma. They are caused by pancreatic ductal disruption following increased pancreatic ductal pressure either due to stenosis, calculi or protein plugs obstructing the main pancreatic ductal system or as a result of pancreatic necrosis following an attack of acute pancreatitis. [2-4] The histology of pseudocysts arising from both acute and chronic pancreatitis is identical. Pseudocysts complicate the course of chronic pancreatitis in 30-40% patients.  This article shall discuss the management of pseudocysts developing on a setting of chronic pancreatitis.
Abdominal pain is the most common symptom of a pseudocyst of the pancreas.  Persistent pain only due to the cyst per se is rare and it is usually due to the underlying chronic pancreatitis. Nausea, vomiting, low-grade fever and weight-loss are the other commonly encountered symptoms.  On clinical examination, an abdominal mass is often palpated depending on cyst size and patient habitus. Rarely, obstructive jaundice develops as a result of a large pseudocyst in the pancreatic head region. All these signs and symptoms are on a background of characteristic signs and symptoms of chronic pancreatitis or of recurrent episodes of acute pancreatitis superimposed on chronic pancreatitis.
Natural history of pancreatic pseudocysts
While understanding the natural course of pseudocysts of the pancreas, the duration and size of cysts need to be considered. Pancreatic pseudocysts of less than 6 weeks duration have a higher chance of spontaneous resolution.  After 6 weeks, the chance of spontaneous resolution decreases significantly; moreover, the incidence of complications tends to rise. 
Similarly the size of pseudocysts correlate well with resolution rates. Cysts smaller than 6 cm resolve without intervention in around 60-80% cases, while only 33% of cysts larger than 6 cm resolve without active intervention.  , 
Pseudocysts in chronic pancreatitis need to be differentiated from cystic neoplasms of the pancreas. Currently, a careful clinical history, modern imaging and an experienced gastroenterologist and / or surgeon interested in the pancreas are the only valuable guides to differentiate pseudocysts from neoplasms. A formal exploration is always justified in cases of doubt.
COMPLICATIONS OF PSEUDOCYSTS IN CHRONIC PANCREATITIS
Rupture of a pseudocyst can have either a favourable or an unfavourable outcome and this depends on whether it ruptures into the gastrointestinal tract, into the general peritoneal cavity or into the vascular system.  ,  Rupture into the gastrointestinal tract either results in no symptoms or leads to melaena or haematemesis that usually requires urgent conservative measures. Rupture into the general peritoneal cavity results in features ofperitonitis and on occasions an associated haemorrhagic shock complicated the situation and mandates emergent surgical exploration. While an internal drainage should always be aimed for, usually a thorough abdominal lavage and external drainage is all that can be achieved safely.
As mentioned above haemorrhage can greatly complicate the course of a pseudocyst.  The morbidity and mortality with such a situation is very high because it can appear without warning and is usually due to erosion of a major vessel in the vicinity of the pseudocyst. Interventional radiology can play an invaluable role both in locating the source of bleeding and in embolisation of the bleeding vessel.  Without prior information of the bleeding point, surgical exploration is hazardous and challenging.
This occurs either spontaneously or after therapeutic or diagnostic manipulations. While infected pseudocyst can initially be treated with conservative means, a majority of patients will require intervention in the form of surgery. Endoscopic treatment is often not effective and even percutaneous catheter drainage often proves ineffective. On exploration, a decision is taken based on intraoperative findings.
While internal drainage should always be the aim,15 an external drainage is necessary in selected situations such as when there is evidence of gross sepsis or when pseudocyst walls are thin and friable.
These occur due to a large cyst in the pancreatic head region obstructing the common bile duct and resulting in obstructive jaundice.  ,  Therapeutic endoscopy with short term biliary endoprosthetic stenting is valuable in this situation. It can be retained till either the cyst resolves or is treated by intervention. However, stenting of the common bile duct cannot be recommended for a duration longer than 6 weeks by which time either the cyst should resolve or be treated by surgical or radiological intervention.
This can result from compression or obstruction of the splenic vein / portal vein either by the cyst alone or in conjunction with underlying chronic pancreatitis.  In this situation, surgery appears to be the only treatment modality available and an appropriate surgical procedure can effectively treat this form of portal hypertension.
No laboratory investigation is diagnostic of a pseudopancreatic cyst. However, raised serum levels of amylase and / or lipase and leucocytosis are often noted. Liver functions are likely to get deranged in the event of biliary compression by the pseudocyst. Blood glucose may be elevated due to underlying chronic pancreatitis or as a result of a severe acute attack of pancreatitis.
On sonography they are seen as rounded, hypoechoeic and well defined structures. In experienced hands, ultrasonography can detect a cyst in the majority of cases.  The ultrasound examination should demonstrate the size, number, position and wall thickness of the cyst. This examination should also define the pancreatic morphology, splenic and portal vein status and the status of the biliary tree and the duodenal status as regards narrowing due to chronic inflammation of chronic pancreatitis.
Computed Tomography (CT)
It offers than 90%) for the diagnosis and other details of pancreatic pseudocysts than ultrasonography which can have limitations due to bowel gas.  Studies have shown that though CT scan is an excellent imaging tool, it is always difficult to differentiate a pancreatic pseudocyst from a cystic tumour of the pancreas.  Furthermore, CT guided fine needle aspiration cytology (FNAC) in cystic lesions of the pancreas offers a sensitivity of around 60% only.  It must be remembered that in most centres of pancreatic surgery, FNAC is not routinely recommended simply because the final diagnosis cannot be reliably established and the decision to operate is anyway based on other findings. Thus it appears that a careful history and clinical examination, combined with a high resolution CT scan, are the best means of differentiating pseudocysts from other cystic lesions of the pancreas.
Endoscopic Retrograde cholangiopancreatography (ERCP)
It can define the pancreatic ductal anatomy and whether a communication exists between the ductal system and the pancreatic pseudocyst. While opinion is still divided, it can help to plan the future line of management.  However we have to take into account the fact that ERCP has serious drawbacks of inducing acute pancreatitis and secondary infection of a sterile pseudocyst  and hence treatment should individualized to the particular case situation.
Magnetic Resonance Cholangiopancreatography (MRCP)
This recent imaging modality has the advantage of being non-invasive and free of radiation hazards and yet offers the possibility of identical information as can be obtained on ERCP. In addition, it can pancreatic parenchymal morphology and blood vessels. Thus it has a distinct potential to replace diagnostic ERCP and could well turn out to be a cost-saving procedure. However results of comparative studies are awaited. 
Endoscopic ultrasonography (EUS)
EUS may be useful in differentiating pseudocysts amenable to endoscopic drainage versus those that would be managed best by percutaneous or surgical drainage.  It has been shown that endosonographic guidance to puncture pseudocysts and then place internal stents is a possibility. These areas, discussed further in the management section of this article, will need further investigation and further technological development. 
Pseudopancreatic cysts are approached by means of surgery, endoscopy or interventional radiology. As discussed previously, intervention is usually indicated when a cyst is greater than 6 cm or has lasted for more than 6 weeks or when obstructive complications such as gastric outlet obstruction, duodenal obstruction, common bile duct obstruction or portal venous obstruction occur. Among other complications, infection, haemorrhage and pain also constitute as common indications for active intervention.
They consist of internal drainage, external drainage or resection procedures.
Cystogastrostomy, cystoduodenostomy and cystojejunostomy are usually performed. The choice is dependent on location of the pancreatic pseudocyst and the philosophy of the surgical team. Internal drainage is indicated when pseudocysts are sterile, non-infected and have a well formed wall for holding anastomotic sutures. Excellent results with ideal indications have been well documented  ,  ,  ,  (Table 1).
TABLE 1 :
Drainage operations for pancreatic pseudocysts - Major series
Author Year Ref. Patient No. Internal drainage External drainage Complications Mortality Martin EW et al 1979 40 100 NA NA Ext. Fistula (< 10% cases NA of external drainage) (reported as low morbidity) Zirngibl H et al 1983 41 148 120 33 Overall recurrence (31.9%) 5.8% O’Malley et al 1985 42 49 31 11 NA 4% Yeo et al 1990 43 39 30 7 NA 0% Bottger T et al 1991 44 145 93 52 Recurrence 9.3% after internal and 55.5% after external drainage 1.1% after internal and 4.7% after external drainage Vitas / Sarr MG 1992 10 46 26 6 NA 0%
NA = Not available
External operative drainage is indicated ingrossly infected pseudocysts and when the cyst wall is immature with thin, friable walls such as following a recent attack of acute pancreatitis. Gross infection is detected by initial aspiration of cyst contents during the course of operative management of a pseudopancreatic cyst. The other indication for a planned surgical external drainage of a pseudocyst is an ineffectively draining percutaneously inserted catheter. This is often observed in situations where pseudocysts contain infected material or in bleeding pseudocysts. Post-operative pancreatic fistulas may develop in approximately 20-40 % of cases and are usually related to exocrine pancreatic secretion.  ,  ,  The majority of these heal spontaneously especially in situations where the proximal pancreatic duct is normal and patent. Parenteral octreotide therapy has been suggested to be beneficial in pancreatico-cutaneous fistulas.  ,  ,  However controlled randomized studies are awaited to draw a final conclusion in this regard.
These are indicated in certain specific situations, namely in the management of a large pseudocyst in the tail of a severely affected chronic pancreatitis gland. A distal pancreatectomy is the preferred procedure in combination with drainage of the pancreatic remnant. Similarly, a pseudocyst superimposed on an inflamed pancreatic head of chronic pancreatitis constitutes an indication for the duodenum preserving pancreatic head resection.  Here again, post-operative pancreatic fistulas are a major problem. However excellent results with very low fistula rates after pancreatic resection are documented in major centres of pancreatic surgery. 
The aim of endoscopic treatment of pancreatic pseudocysts is to create an internal communication between the cyst and the gastric or intestinal lumen. Biliary, gastric outlet, duodenal, and vascular obstruction are the other indications for therapeutic endoscopic procedures. Two approaches are adopted depending on anatomical considerations. If the cyst is communicating with the main pancreatic duct, a transpapillary approach might be adopted. A transmural approach is indicated where a direct apposition of the pseudocyst against the stomach or duodenal wall is seen endoscopically. While long term results are not yet convincing, initial technical success rates over 90% have been reported in specialized centres  ,  (Table 2).
TABLE 2 :
Results of endoscopic therapy for pancreatic pseudocysts - Major series
Author Year Ref. Patient No. Transmural drainage Transpapillary Complications drainage Pain relief (months of follow up) Cremer et al 1989 37 33 33 Nil 9% (bleeding, infection, peritonitis) Recurrence (14%) 88%
Barthet et al 1993 45 71 78 Nil 15% (bleeding, perforation) Recurrence (18%) NA Huibregts and Smits 1994 46 37 Nil 37 16% (bleeding, perforation fever, apnoea) Recurrence (5%) 87% Soehendra et al 1995 38 53 24 33 11% (bleeding, gastric,pancreatitis, abscesses) 76%
Beckingham IJ et al 1999 47 34 24
Nil Recurrence (7%) NA Vitale GC et al 1999 48 29 27 9 Eventual surgery (17%) NA
However, therapeutic endoscopic treatment of pseudopancreatic cysts has its own set of complications. The most frequently encountered complications are bleeding, peritonitis, secondary cyst infection and E.R.C.P - related complications such as post-E.R.C.P. acute pancreatitis and perforations.  ,  The other disadvantage of endoscopic therapy is the lack of tissue from the pseudocyst wall for histopathological analysis.
The role of interventional radiology
The indications for percutaneous catheter drainage are similar to those of surgical external drainage. A symptomatic pseudocyst with immature walls, frequently resulting from an attack of necrotizing pancreatitis, is one such indication. However, the patients have to be carefully selected for this therapeutic approach. In critically ill patients unfit for surgery, it can be a valuable asset as initial treatment modality till such time that either the pseudocyst resolves or the patient is fit enough for further surgical management. The use of percutaneous catheter drainage is not indicated where necrotic tissue is a possibility since drainage is likely to be inadequate resulting in further complications and sequelae.
Pancreatic fistula is always a possibility with percutaneous catheter drainage.  As with endoscopic modalities, this technique carries the disadvantage of lack of tissue from the pseudocyst wall for histopathological analysis.
Treatment of pseudocysts of pancreas in chronic pancreatitis is dictated by a variety of factors. Important among them are the duration of the cyst existence, cyst size, wall thickness and the presence of symptoms. Communication with the main pancreatic duct is another decisive factor from the therapeutic standpoint. While surgery has stood the test of time in the effective management of pseudocysts, newer modalities of interventional radiology and therapeutic endoscopy appear promising and in selected situations they appear to play a valuable role. However, long term results of these modalities should be compared with surgical options to assess their real impact in the management of pancreatic pseudocysts. A significant drawback of these modalities is the lack of histology since tissue cannot be obtained with the available technology. In cases of doubt, a surgical exploration with intra-operative frozen section diagnosis, should be performed without hesitation. In view of their very nature and the range of possible complications, pseudocyst management should be under the overall control of an experienced surgical unit. As things stand today, while a close interaction between the surgeon, endoscopist and the interventional radiologist is ideal, treatment of each patient is best individualized depending on the available local expertise and infrastructure.
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