Pseudocysts are common lesions of the pancreas that arise from pancreatic ductal disruption. They range from simple, self-resolving cysts to complex, life-threatening cysts that present challenging management decisions. The Atlanta International Symposium on Acute Pancreatitis defined pancreatic pseudocysts as fluid collections more than 4 weeks old that are surrounded by a nonepithelial wall of fibrous or granulation tissue arising as a consequence of acute pancreatitis, chronic pancreatitis, or pancreatic trauma. Pseudocysts complicate 10% to 26% of acute pancreatitis cases and 20% to 40% of chronic pancreatitis cases; they are typically round or ovoid on imaging and nonpalpable on physical examination. Because of the disruption of the pancreatic duct, they are rich in pancreatic enzymes such as amylase. Acute fluid collections complicate more than 50% of cases of acute pancreatitis and are distinct from pseudocysts because acute fluid collections are irregular in shape and lack a well-defined wall. In the absence of infection, acute fluid collections are managed expectantly, because most resolve spontaneously, whereas the management of pseudocysts more often requires endoscopic, percutaneous, or surgical drainage.
Distinguishing Pseudocysts from Pancreatic Cystic Neoplasms
Careful exclusion of a pancreatic cystic neoplasm is mandatory before considering draining pseudocysts. Pseudocysts account for at least 75% of all pancreas cysts, but they can be difficult to distinguish from pancreatic cystic neoplasms, retention cysts, and congenital cysts, especially in patients without a clear history of pancreatitis. Retention cysts are nonneoplastic localized areas of dilation of the pancreatic duct owing to a ductal obstruction from an obstructing neoplasm, stricture, or stone. Like pseudocysts, retention cysts are common complications of chronic pancreatitis. Pancreatic cystic neoplasms include those with malignant potential such as mucinous cystic neoplasms, intraductal papillary mucinous neoplasms, solid pseudopapillary neoplasms with cystic components, pancreatic adenocarcinoma, or neuroendocrine tumors with cystic degeneration, and benign serous cystadenoma. Many malignant pancreatic cysts are well treated with surgical resection; however, intervention to drain a cystic neoplasm mistakenly diagnosed as a pseudocyst can compromise any subsequent attempt at operative resection.
A careful clinical history of preceding pancreatitis of a known origin or established chronic pancreatitis can assist in distinguishing between pseudocysts and potential cystic neoplasms. However, this may not be helpful in all cases. Warshaw and colleagues reported on 12 years of experience with pancreatic cystic neoplasms and noted that 37% of lesions had been misdiagnosed as pseudocysts before operation. They found that clinical factors such as abdominal pain and pancreatitis were unhelpful in distinguishing between the two lesions, because both patients with cystic neoplasms and pseudocysts commonly experienced these symptoms. Warshaw and others also found cyst diameter to be a poor distinguishing factor as the mean size of neoplastic cysts is frequently similar to that of pseudocyts. Computed tomography (CT) and magnetic resonance imaging may be helpful in identifying dependent debris within the lesion, suggestive of a pseudocyst, or rim calcification, indicative of neoplasia. External microlobulated morphology and internal septae were more common in neoplasms than in pseudocysts, but neither of these findings attained significance in one study utilizing magnetic resonance imaging. Further, Chalian and colleagues found that CT attenuation was significantly higher in pseudocysts than in mucin-containing cysts (mean of 18.9 HU for pseudocysts, 13.0 HU for mucinous cystic neoplasms, and 11.4 for intraductal papillary mucinous neoplasms), further helping to distinguish these lesions noninvasively.
Endoscopic ultrasonography (EUS) permits visualization of cystic lesions that are within close proximity to the gastrointestinal (GI) lumen and offers the ability for tissue sampling and cyst fluid analysis before pursuing drainage of a potential pseudocyst. Van der Waaij and colleagues analyzed 12 different studies comprising data from 450 patients with pancreatic cyst fluid analysis and found that an amylase level of less than 250 U/L had 98% specificity for serous cystadenoma, mucinous cystadenoma, or mucinous cystadenocarcinoma and virtually excluded the diagnosis of pseudocyst. Carcinoembryonic antigen less than 5 ng/mL showed a specificity of 95% for pseudocyst and serous cystadenoma as did carbohydrate-associate antigen 19 (CA 19-9) concentration less than 37 U/mL with a specificity of 98%. All of these cyst fluid biomarkers showed sensitivities of 50% or less; therefore, these tests are most helpful when the measured value falls below the stated thresholds (ie, the negative predictive value). There are several promising new candidates for cyst fluid biomarkers, such as glycosolation variants of mucins and carcinoembryonic antigen cell adhesion molecules. It would seem that these diagnostic difficulties would favor surgical drainage over percutaneous or endoscopic drainage of cystic lesions, because surgery affords a more generous cyst wall biopsy; however, the magnitude of this benefit is questionable. In one study, the epithelial lining of cystic lesions was partially (5%–98%) missing in 40% to 72% of all major tumor types, implying that even biopsy of a cyst during surgical cystenterostomy can lead to a missed diagnosis of a neoplasm. Currently, no single test can rule out a pancreatic cystic neoplasm; rather, a careful assessment including a detailed clinical history, radiologic studies, and EUS-guided cyst fluid analysis is the most reliable method for distinction.
Indications for Drainage of Pancreatic Pseudocysts
The natural history of pseudocysts and the complications associated with conservative management by observation have traditionally demanded intervention to drain pseudocysts. This is largely based on the work of Bradley and colleagues, who followed patients with pseudocysts until cyst resolution or the occurrence of complications such as rupture, abscess, jaundice, or hemorrhage. During the observation period, 41% of their patients experienced complications with cyst resolution occurring in 20%. They also demonstrated that observation past 7 weeks had more risk than operative management. Their work contributed to an oft-quoted guideline recommending that physicians actively drain all pseudocysts that persisted longer than 6 weeks. More recent work suggests that longer periods of observation are safe and effective in permitting spontaneous resolution in up to 86% of patients with a 3% to 9% rate of serious complications developing during an average of 1-year expectant follow-up.
Further, traditional guidelines have held that pseudocysts greater than 6 cm in diameter should be drained because they showed lower rates of spontaneous resolution and exposed patients to greater risks of complications than smaller pseudocysts. Although data regarding pseudocyst size and outcome are mixed, a smaller size (<4 cm) is an important predictor of spontaneous resolution. One study of 36 patients with asymptomatic pseudocysts found that 67% of pseudocysts greater than 6 cm in diameter and 40% of pseudocysts less than 6 cm required surgical treatment. Cheruvu and colleagues had differing results, finding that the median pseudocyst size of those requiring intervention was similar (8 cm) to those successfully managed conservatively (7 cm), arguing that pseudocyst size is a less important factor in the eventual outcome. Nguyen and colleagues similarly found that size greater than or less than 6 cm had no effect on rates of spontaneous resolution, need for operative management, complications, recurrence, or mortality. The heterogeneity of findings regarding outcomes and pseudocyst size highlight that criteria for pseudocyst drainage based on cyst size are not appropriate. Rather, persistent pain, gastric or duodenal obstruction, biliary obstruction, ascites, pleural effusion, enlarging size on serial imaging, signs of pseudocyst infection or bleeding, or the possibility of a pancreatic cystic malignancy are more important factors in considering interventions for pseudocyst drainage.
Indications for Drainage of Pancreatic Pseudocysts
The natural history of pseudocysts and the complications associated with conservative management by observation have traditionally demanded intervention to drain pseudocysts. This is largely based on the work of Bradley and colleagues, who followed patients with pseudocysts until cyst resolution or the occurrence of complications such as rupture, abscess, jaundice, or hemorrhage. During the observation period, 41% of their patients experienced complications with cyst resolution occurring in 20%. They also demonstrated that observation past 7 weeks had more risk than operative management. Their work contributed to an oft-quoted guideline recommending that physicians actively drain all pseudocysts that persisted longer than 6 weeks. More recent work suggests that longer periods of observation are safe and effective in permitting spontaneous resolution in up to 86% of patients with a 3% to 9% rate of serious complications developing during an average of 1-year expectant follow-up.
Further, traditional guidelines have held that pseudocysts greater than 6 cm in diameter should be drained because they showed lower rates of spontaneous resolution and exposed patients to greater risks of complications than smaller pseudocysts. Although data regarding pseudocyst size and outcome are mixed, a smaller size (<4 cm) is an important predictor of spontaneous resolution. One study of 36 patients with asymptomatic pseudocysts found that 67% of pseudocysts greater than 6 cm in diameter and 40% of pseudocysts less than 6 cm required surgical treatment. Cheruvu and colleagues had differing results, finding that the median pseudocyst size of those requiring intervention was similar (8 cm) to those successfully managed conservatively (7 cm), arguing that pseudocyst size is a less important factor in the eventual outcome. Nguyen and colleagues similarly found that size greater than or less than 6 cm had no effect on rates of spontaneous resolution, need for operative management, complications, recurrence, or mortality. The heterogeneity of findings regarding outcomes and pseudocyst size highlight that criteria for pseudocyst drainage based on cyst size are not appropriate. Rather, persistent pain, gastric or duodenal obstruction, biliary obstruction, ascites, pleural effusion, enlarging size on serial imaging, signs of pseudocyst infection or bleeding, or the possibility of a pancreatic cystic malignancy are more important factors in considering interventions for pseudocyst drainage.
Drainage Techniques
The method of drainage is based primarily on local expertise with the endoscopic approach being favored for simple pseudocysts that are in close proximity to the gastric or duodenal wall. It is considered to be the first-line approach. A percutaneous approach is reserved for those collections that do not communicate with the pancreatic duct or are not adjacent to the GI lumen, or in patients who are not optimal candidates for surgery. If regional expertise in endoscopy is not available, then surgical drainage for complex pseudocysts and walled-off organized pancreatic necrosis is preferred. There are many advantages to endoscopic drainage of pseudocysts: The ability to place multiple internal drains, irrigation via a nasocystic catheter, treating downstream pancreatic ductal obstruction via endoscopic retrograde cholangiopancreatography, direct endoscopic necrosectomy, and the lack of known sequelae if a persistent fistula develops at the site of the cystenterostomy. Indeed, the latter may help to reduce the risk of pseudocyst recurrence by promoting drainage of pancreatic juices in the case of a “disconnected tail syndrome.” Percutaneous and surgical options for drainage are indeed associated with greater morbidity.
Transmural endoscopic drainage is generally performed when the pseudocyst is within 1 cm of the gastric or duodenal lumen. Smaller, symptomatic pseudocysts more than 1 cm from the GI lumen may be appropriate for transpapillary drainage if communication is evident on pancreatography. In our experience, a combined transmural or transpapillary approach is not generally required for successful resolution of most pseudocysts. Periprocedural prophylactic antibiotics with a fluoroquinolone or other broad-spectrum antibiotic is recommended to reduce the incidence of pseudocyst infection. Antibiotics can be continued for 3 to 5 days after the procedure.
Techniques of Endoscopic Drainage
Transpapillary drainage
In general, transpapillary stenting is the sole means of drainage if the pseudocyst is smaller than 6 cm and there is communication with the main pancreatic duct, or if transmural drainage is not feasible owing to distance (eg, >1 cm from the GI lumen) or is contraindicated (eg, significant coagulopathy). Ancillary interventions include major or minor papilla pancreatic sphincterotomy, judicious dilation of downstream pancreatic duct strictures, and placement of a large-bore pancreatic duct stent preferably across any ductal disruption or into the pseudocyst cavity ( Fig. 1 ).
Transmural
EUS or non–EUS-guided techniques may be utilized. Non–EUS-guided transmural drainage requires not only close proximity of the pseudocyst to the GI lumen, but also an endoscopically visible bulge.
Non–EUS-guided transmural drainage
Endoscopic needle localization (ENL) of the point of maximal endoscopic bulge aims to confirm an appropriate location before cystenterostomy tract dilation and stent placement ( Fig. 2 ). The two methods of ENL that have been well-described are diathermic puncture and the Seldinger technique. Diathermic puncture involves inserting a 22-gauge, precurved biliary aspiration needle mounted in a 7-Fr catheter (HBAN22, Cook Endoscopy, Winston-Salem, NC, USA) or a Cystotome (Cook Endoscopy, Inc.) that is a 10-Fr catheter with a diathermic ring and a 5-Fr inner catheter housing a low-profile, 0.38-inch needle knife to facilitate close apposition of the pseudocyst to the gut lumen. For initial puncture, the needle knife should be directed perpendicularly to the axis of maximal endoscopic bulge with pure cutting current recommended by some authorities. The return of blood upon needle puncture is concerning for entry into either a vascular structure, such as a pseudoaneurysm, or a blood vessel in the wall of the pseudocyst. Repuncture at a different site with bloody return warrants consideration for terminating the procedure and reevaluating for a pseudoaneurysm or portal hypertension with perigastric varices. Stroking of the needle knife is not recommended because a cut of even a few millimeters on the cyst bulge can enter an adjacent gastric vessel wall. Electrocautery should be discontinued immediately upon entry of the needle knife into the cyst cavity to avoid thermal injuries to surrounding structures. Once a site is found with suitable fluid return, limited contrast is injected under fluoroscopic guidance to confirm position within the pseudocyst.
The Seldinger technique for entry involves creating an initial puncture with an 18-gauge needle and then a 0.035-mm guidewire is placed through the needle, which allows an 8- to 10-mm balloon tract dilation over the guidewire before stent placement. This technique was studied in 94 consecutive patients with comparable efficacy to needle-knife entry (95% vs 92%, respectively), although it showed a significantly lower bleeding complication rate of 4.6% compared with 15.7% with diathermic puncture.
Following deep access with a guidewire and 2 to 3 curls of the wire within the pseudocyst cavity, the needle or catheter is exchanged for an 8- or 10-mm dilating balloon. Inflation is done under fluoroscopic guidance making sure to visualize the waist between the gut lumen and pseudocyst to ensure adequate cystenterostomy tract dilation. Many endoscopists prefer double pigtail stents to reduce migration, and they place 2 or more 10-Fr stents of differing lengths and angles of insertion, especially in large cysts, to ensure drainage of the most dependent and distal portions ( Fig. 3 ). Stents are removed at the time of pseudocyst resolution, which is generally 4 to 6 weeks. Undrained segments related to internal debris or septations may lead to nonresolution.
EUS-guided transmural drainage
Traditionally, lack of a pseudocyst bulge into the GI lumen was considered a contraindication to endoscopic drainage. EUS may be utilized to mark a site for duodenoscopic drainage and to assist in excluding perigastric varices ( Fig. 4 ). However, a single-step approach is currently the most commonly utilized method and permits pseudocyst puncture under direct ultrasound guidance. After puncture with a 19-gauge needle, the stylet is withdrawn followed by placement of a .035-inch guidewire. The cystenterostomy, tract dilation, and stent insertion are similar to those described for the non–EUS-guided technique. Passage dilators without the use of electrocautery can also be utilized for tract creation, but in cases where there is minimal to no endoscopically visible bulge and “thinning” of the gastric wall, electrocautery is still required (authors’ personal observation).
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