Pancreatic Pseudocyst

Etiology

Pseudocysts are formed when disruption of the main pancreatic duct or its branches, either from inflammation or direct injury, causes extravasation of pancreatic enzymes into the parenchyma and eventually forms a distinct collection. Pseudocysts arise as a complication of pancreatitis. Therefore, it follows that the causes of pseudocyst formation are the same as the causes of pancreatitis. It appears that alcohol-related pancreatitis is the major cause of pancreatic pseudocyst formation in countries where alcohol consumption is higher as it contributes to over 70% of the cases. The remaining causative factors are biliary stones, trauma, or idiopathic.

A pseudocyst is formed following an episode of acute pancreatitis, often within 4 to 6 weeks of that episode, with a well-defined wall lined by granulation or fibrous tissue. They are filled with amylase rich fluid. About one-third of pseudocysts are located near the head of the gland, and the remaining two-thirds occur in the tail. The pathogenesis of a pseudocyst formation in chronic pancreatitis is not well understood, but it may involve acute exacerbation of underlying pancreatitis with new calculus or protein plug formation in the pancreatic ducts.[3]

Epidemiology

Pseudocysts can occur after pancreatitis in any age group. The incidence of pseudocysts is higher in males as it follows the incidence of pancreatitis, which is slightly male predominant. In acute pancreatitis, the incidence of pseudocysts ranges from 5% to 16%. Pseudocysts tend to be more common in the setting of chronic pancreatitis, with incidence rates between 20% to 40%. This can be explained by its long course posing an increased risk of damaging the pancreatic ducts with fibrosis, calculi, or protein plug formation. Data collected from over 357 admissions at Wayne University Hospital in Detroit for pancreatic pseudocyst recognized that the majority of the cases were alcohol-induced (70%) followed by biliary tract disease (8%), trauma (6%), and the remaining attributed to the idiopathic cause.[4][5][6]

Pathophysiology

Injury to the pancreatic ducts, either from pancreatitis or direct trauma, can lead to extravasation of the pancreatic fluid. In some instances, this fluid organizes into a discrete collection, confined by walls of adjacent organs such as the stomach, pancreas, omentum, and colon, forming a pseudocyst. It can take anywhere between 4 to 6 weeks for the pseudocyst wall to mature. Up to two-thirds of pseudocysts have demonstrable connections to the pancreatic duct. In the remaining one-third of cases, an inflammatory reaction can sometimes seal off the connection making it difficult to identify. The significance of this connection will be discussed in detail under management.[7][6]

Histopathology

In the proper clinical scenario, imaging findings of a well-defined cystic mass near the pancreas is almost certainly indicative of a pancreatic pseudocyst. However, histopathology may be required to differentiate a pseudocyst from malignant cystic lesions, most commonly mucinous cystadenoma. EUS guided fine needle aspiration can be used to obtain a tissue sample to identify cyst wall histology and quantify tumor marker levels of the cyst fluid.

Depending on which part of the cyst is sampled, the histological tissue identified may vary.  The biopsied areas may contain any combination of benign pseudocyst tissue, carcinoma in situ, or areas of advanced malignancy. Therefore, a negative biopsy does not necessarily rule out malignancy. Given this variability, it is recommended to use histological sampling in conjunction with tumor marker levels to increase the accuracy of diagnosing a malignant cyst. A CEA level of greater than 400 ng/mL within the cystic fluid strongly suggests a mucinous lesion; these levels are usually lower in a pancreatic pseudocyst.[8][9][10]

History and Physical

There are no specific symptoms that are pathognomonic of pseudocysts. However, the presence of vague, chronic abdominal pain in someone with a recent bout of pancreatitis should always raise suspicion as the diagnosis.

Some of the signs and symptoms that are suggestive of pseudocyst are:

• Persistent abdominal pain
• Anorexia
• New abdominal mass after an episode of pancreatitis
• Jaundice or shock (less commonly)

Findings that are of limited sensitivity:

• Abdominal tenderness
• Palpable abdominal mass
• Signs of peritonitis, including guarding and rigidity (in case of a ruptured cyst) 
• Fever
• Scleral icterus
• Pleural effusion[3] 

Evaluation

With serum enzyme levels of limited diagnostic utility, identification of a pancreatic pseudocyst is usually made with the combination of high clinical suspicion and imaging studies. Transabdominal ultrasound has a sensitivity of around 70% to 90% and is often used as the initial imaging study due to its portability, ease of use, and cost. The drawback, however, is that the study is user-dependent, and the accuracy of findings may vary considerably based on the user's expertise.

The better option for initial imaging is a contrast-enhanced CT of the abdomen. It is the modality of choice with a remarkable sensitivity of 82% to 100% and a specificity of around 98%. There are many advantages of using a CT scan over an ultrasound; it allows for better visualization of surrounding structures, helps identify evidence of biliary stones or calcifications, and helps discern debris from areas of necrosis. All of which aide in distinguishing pseudocysts from areas of walled of necrosis (WON). The major limitation of using a CT scan is its inability to distinguish between a pseudocyst and neoplastic cystic lesions.

Endoscopic ultrasound (EUS) proves resourceful in this regard as it is a minimally invasive procedure that allows for close up, detailed images of the pancreas. EUS also allows for the endoscopist to perform diagnostic and therapeutic drainage of the cyst. Findings suggestive of a cystic neoplasm includes a cyst wall thickness greater than 3 mm, multiple septations, the presence of a solid mass or nodule, and cystic dilation of the main pancreatic duct. An MRI-MRCP is the most accurate tool to study the anatomy of the pancreatic ducts. It is superior to CT scan imaging in characterizing debris within the pseudocyst. However, MRI-MRCP is not routinely used because a CT scan typically offers adequate diagnostic information. Predrainage MRI-MRCP can be useful in situations where identifying the type of debris is essential to avoid complications related to infection or bleeding. Less commonly, this imaging study can be used to characterize complex ductal anatomy to facilitate pseudocyst drainage.[11][12][13]

Treatment / Management

Spontaneous resolution of pseudocysts is common, especially for those that occur after an episode of acute pancreatitis. Since stable, non-enlarging pseudocysts rarely cause any symptoms, the gold standard for the treatment of uncomplicated pseudocysts is conservative management. This includes analgesics and antiemetics as needed and a low-fat diet. Such patients usually have interval imaging for early detection in case the size of the pseudocyst does increase or if complications develop.

On the other hand, pseudocysts that develop as a complication of chronic pancreatitis rarely resolve spontaneously. Specific factors that correlate with a lower chance of spontaneous resolution include the presence of multiple cysts, cysts located near the tail of the pancreas, coexistence of other local anatomic complications such as strictures or calcifications of the pancreatic ducts, and the progressive increase in the size of the cyst. Urgent intervention may be needed if patients develop peritonitis, infection, bleeding, or gastric outlet obstruction. Alarming symptoms that should raise the suspicion for these complications include acutely worsening abdominal pain, persistent nausea, vomiting, inadequate oral intake, fevers, chills, or hypotension.

The three categories of invasive interventions are percutaneous, endoscopic, and surgical drainage or excision. Ideally, any intervention should be delayed to around six weeks after the inciting pancreatitis episode, in the absence of complicating factors, to allow the pseudocyst wall to thicken and mature. At this point, the pseudocysts are more amenable to penetration and drainage. It is important to note, however, that pseudocysts of any size or duration require more immediate intervention if it is thought to be the cause of life-threatening illness.

Percutaneous Drainage (PD)

Percutaneous drainage is performed with either ultrasound or CT guidance. A pigtail catheter is placed into the pseudocyst and is left in place until the fluid output is minimal. PD can cause significant discomfort to the patient as the catheter tends to clog and may need frequent repositioning. It is contraindicated in patients with strictures of the pancreatic duct and those who cannot manage catheter care at home. There have been multiple studies evaluating the efficacy of PD compared to the other treatment modalities available. One of the most extensive studies comparing Surgical Drainage (SD) and PD found that, although they had similar success rates, SD had fewer complications in terms of mortality, duration of hospital stays, and rates of re-intervention. Compared to endoscopic drainage, PD was inferior with regards to residual fluid collections, frequency of re-intervention, and the need for surgery. Based on these studies, PD should only be considered in critically ill patients who cannot tolerate surgical or endoscopic procedures or for patients with an immature infected or complicated pseudocyst as PD does not require wall maturation before the intervention. 

Endoscopic Drainage

Endoscopic drainage methods are becoming the preferred treatment approach because it is less invasive than surgery and yields high long-term success rates. The aim is to create a canal that helps to drain the pancreatic pseudocyst into the gastrointestinal tract, avoiding the need to place an external drain. Construction of the canal can be done either through the trans papillary method (TPD) using ERCP or directly across the stomach or duodenal wall with transmural (TSM) drainage.

1.Transpapilliary Drainage (TPD)

Transpapillary drainage is an option when there is a communicating tract between the pseudocyst and the main pancreatic duct or when the cyst is too far away from the gastrointestinal lumen to pursue TSM drainage. In this technique, a catheter is threaded through the pancreatic duct, and a stent is deployed within the communicating tract between the pseudocyst and the lumen of the pancreatic duct under ERCP guidance. This facilitates pseudocyst drainage and decompression. If strictures are encountered along the pancreatic duct, balloon dilation is performed to open the lumen and allow passage of the catheter. TPD is less likely to be successful for cysts located distally if multiple cysts are present, or multiple pancreatic duct strictures impair the ability to pass the catheter.

An advantage of using the TPD technique is the ability to dilate other pancreatic duct strictures encountered while threading the catheter to access the pseudocyst-pancreatic duct communicating tract. Alleviating strictures along the pancreatic duct could potentially reduce the chance of further pseudocyst formation in the future. TPD has a success rate, which ranges from 81% to 94%. However, a recent multicentre study published in 2016 showed no benefit in treatment outcomes in patients undergoing TPD vs. EUS-guided transmural drainage. TPD was associated with lower rates of long-term cyst resolution after a mean follow up of 200 days.

2.Transmural Drainage (TSM)

TSM is performed across the stomach or the duodenal wall using EUS or the conventional endoscope to guide drainage of the pseudocyst. With recent advances in technology, EUS guided drainage has mostly replaced the use of conventional endoscopy. Conventional endoscopy relies on the presence of a bulge in the gut wall caused by a compressing pseudocyst to identify an ideal puncture site. The advantage of using EUS is the ability to identify and access a pseudocyst that is non-bulging (which occurs in approximately 42% to 48% of cases), pseudocysts that are adjacent to, but not directly abutting the gastrointestinal wall and pseudocysts that are located more distally along the pancreas. Additionally, EUS helps identify and avoid overlying blood vessels, and thus, decreasing the risk of bleeding complications. Once the puncture site is established, a needle is inserted into the pseudocyst, and positioning is confirmed using fluoroscopy. After the cyst-gut tract is confirmed, it is dilated pneumatically, and multiple pigtail stents are deployed for drainage. In two randomized control trials comparing EUS with non-EUS guided transmural drainage, the technical success rates were better in EUS guided drainage; ~95% versus 59%. The major adverse events associated with TSM are hemorrhage, perforation, and infection. In summary, TSM is indicated when the pancreatic duct anatomy is disrupted or complicated with stricture formation. With management archetype moving towards less invasive techniques, the endoscopic approach is gaining popularity for treating pseudocysts. EUS assisted techniques are associated with a higher success rate and a decreased percentage of serious complications.

Surgical Drainage

Historically surgical drainage, which includes cystogastrostomy, Cystoduodenostomy, or cystojejunostomy, was the method of choice for pancreatic pseudocyst drainage. However, with evolving endoscopic techniques, surgical drainage is now limited to certain situations such as recurrent pseudocysts, pseudocysts of uncertain origin, resection of a malignant cyst, or pseudocysts that are difficult to access endoscopically. Clinical features that should raise concerns for malignancy are weight loss, a palpable mass, multilocular pseudocysts, thick walls, and an elevated CEA level in the pseudocyst fluid. For surgical drainage, either the open or laparoscopic method can be opted for as both are effective; however, the laparoscopic approach carries lower morbidity and mortality. A systematic review found that laparoscopic drainage is associated with a 98.3% success rate, 2.5% recurrence rate, a mean hospital stay of 5.7 days, and a less than 2% complication rate. A retrospective study done in 2009 comparing endoscopic drainage with surgical drainage (open or laparoscopic) found a similar rate of complications, but surgical drainage was associated with a higher treatment success rate. In conclusion, surgical drainage is a safe alternative to other less invasive procedures and is reserved for cysts that need a wider stoma for drainage, resection of pancreatic necrosis, or cysts of unknown etiology.

In summary, the treatment of choice depends on the individual patient profile, and it is essential to understand the risks and benefits associated with each treatment modality.[11][12][13](B2)

Differential Diagnosis

1. Pancreatic necrosis or abscess: Necrosis of the pancreatic and peri-pancreatic tissue. Presents in patients with acute pancreatitis with sepsis-like physiology who fail to recover with conservative management.
2. Pancreatic Pseudoaneurysm: can also be seen as a complication of pancreatitis caused by erosion of the arteries, leading to a rapid increase in the cyst’s size, a sudden drop in hemoglobin, and upper GI bleeding.
3. Pancreatic cystic neoplasm: Appears as a multiloculated cyst with thick walls and elevated carcinoembryonic antigen (CEA) levels in the cystic fluid. Clinical features include loss of weight and appetite. 
4. Other differential diagnoses include extra-pancreatic pathologies such as peptic ulcer disease, gastric cancer, bowel obstruction, ovarian tumor/cysts, acute myocardial infarction, or pneumonia.[3]

Prognosis

Spontaneous resolution of pseudocyst is common, especially for those that occur after an episode of acute pancreatitis. The maturation of pancreatic pseudocysts takes approximately 2 to 6 weeks, and during this time, 33% of cysts resolve spontaneously.

Complications

The goal is to avoid complications which include:

1. Infection 
2. Rupture into the gastrointestinal tract causing signs and symptoms of bleeding 
3. Free rupture into the peritoneal cavity causing abdominal pain, peritonitis, or even death
4. There have been case reports of large pseudocysts causing increased intra-abdominal pressure, which can present with orthopnoea, dyspnea, abdominal pain, distention, and new organ failure.
5. Pancreatic pseudoaneurysm
6. Compression of the surrounding structures causing biliary complications or portal hypertension[3]