Pancreatic cystic neoplasms represent a wide spectrum of invariably benign to precancerous and malignant tumors. Endoscopic ultrasound-guided pancreatic cyst ablation with ethanol and/or paclitaxel offers a nonoperative treatment for patients refusing or not eligible for surgery. Histopathology after resection in these patients has shown variable degrees of cyst epithelial ablation ranging from 0% to 100%. Future research investigating the safety of this procedure, modifications of reported ablation techniques, choice and number of the lavage agents used, and criteria to optimize selection of the appropriate pancreatic cysts for treatment is needed.
Pancreatic cystic neoplasms
Classification
Cysts within the pancreas may be broadly classified as (1) those complicating acute or chronic pancreatitis (acute fluid collections and pseudocysts) and (2) neoplasms lined by epithelium. Because acute fluid collections and pseudocysts are not lined by epithelium, they are uniformly benign with no malignant potential. The epithelium that outlines pancreatic cystic neoplasms (PCNs) may have negligible malignant potential (serous cystadenomas) or represent either premalignant (ie, intraductal papillary mucinous neoplasms [IPMNs] or mucinous cystadenomas [MCNs]) or malignant (ie, invasive IPMNs or mucinous cystadenocarcinomas) tumors.
MCNs are usually associated with the production of extracellular mucin and variable degrees of cyst wall epithelial atypia. These cysts are characterized by the presence of ovarian stroma underlying the mucinous columnar cyst epithelium, which differentiates MCNs from IPMNs. IPMNs are mucinous cystic lesions that arise from the main pancreatic duct (MD-IPMN), one of its side branches (SB-IPMN), or both sites (mixed IPMN). Unlike MCN, these cysts are distinctively associated with ductal ectasia and intraductal papillary growth.
Pancreatic Cysts: Asymptomatic and Symptomatic
Pancreatic cysts are encountered in clinical practice either as asymptomatic lesions found incidentally on imaging studies or as lesions initially noted during evaluation of symptoms such as abdominal pain, weight loss, and jaundice. The routine use of abdominal imaging studies for symptoms such as nonspecific abdominal pain has led to increased recognition of pancreatic cysts; however, the exact prevalence of pancreatic cysts is unknown. Recent magnetic resonance imaging (MRI) and computerized tomography (CT) studies indicate a prevalence of pancreatic cysts ranging between 2.4% and 14%.
Surgery or Surveillance?
Consensus guidelines and expert opinion recommend surgical resection of mucinous pancreatic cysts (ie, MCNs and IPMNs) that are symptomatic, larger than 3 cm in diameter, possess mural nodules, or involve the main pancreatic duct (ie, MD-IPMN). However, even at experienced centers, reported surgical morbidity and mortality rates for PCNs are 20% to 40% and up to 2%, respectively. Because of operative risk, there has been increasing interest within the last decade to evaluate the feasibility of nonoperative surveillance of low-risk PCNs (particularly SB-IPMNs ), which do not meet definite criteria for surgical resection. These studies evaluating the surveillance of low-risk PCNs have demonstrated that patients with asymptomatic SB-IPMNs measuring less than 3 cm in diameter and without mural nodules can be safely followed by using a combination of close follow-up of patient symptoms and imaging studies (ie, MRI or endoscopic ultrasonography) performed at least annually. This practice has been adopted by most physicians who treat these patients.
Are There Alternatives?
Although surgery or surveillance alone may be optimal management for most patients with PCNs, there has been increased interest in a minimally invasive technique to treat these lesions. Pancreatic cyst ablation, a minimally invasive technique, may be an attractive option to some patients, particularly for patients with multiple preoperative comorbidities deemed high-risk for surgical intervention. The purpose of this review is to summarize the rationale, technique, and available data for pancreatic cyst ablation.
Potential benefits and risks for pancreatic cyst ablation
Benefits
Decreased malignant potential
Endoscopists routinely perform polypectomy on colon adenomas to arrest their potential neoplastic transformation, and studies have documented that this technique decreases subsequent risk of development and death from colon cancer. A similar but largely unproven rationale underlies the endoscopic therapy for Barrett neoplasia to prevent esophageal cancer. The malignant potential of PCNs, such as MCNs and IPMNs, arise from the cyst epithelial lining. Hence, the destruction of the epithelial lining of PCNs may abate or completely remove the neoplastic potential. However, this hypothesis of the potential benefit of nonoperative therapy for PCNs remains only theoretical.
Decreased costs over time
Surveillance of pancreatic cysts is most commonly performed every 1 to 2 years with imaging studies, such as CT or MRI. However, this surveillance is expensive. If ablation could be documented to be effective and durable, surveillance intervals could theoretically be lengthened or completely stopped. However, the technique of pancreatic cyst ablation is still in its infancy and whether the other still evolving nonoperative surveillance patterns of PCNs can be changed following ablation is still unknown.
Psychological benefit to the patient
In some patients, knowledge that they possess a premalignant cyst can provoke significant anxiety. This anxiety can be augmented if the cyst does not meet the criteria for surgical resection or the patient is not a candidate for surgery because of comorbidities. In these patients, cyst ablation may allay some fears and provide some hope that an attempted intervention is performed for the lesion.
Risks
Complications
Adverse events associated with endoscopic pancreatic cyst ablation may include outcomes from either endoscopy or injection of ablative agents. The incidence and management of these outcomes are discussed subsequently.
Incomplete ablation
During colonoscopy, endoscopic polypectomy may be incomplete and leave residual adenoma. Similarly, ablation of Barrett esophagus may not completely destroy the metaplastic intestinal epithelium. After pancreatic cyst ablation, some epithelium may remain untreated and therefore continue to harbor malignant potential.
High initial treatment costs
If a decision is made to ablate a pancreatic cyst, then there will be increased upfront costs associated with 1 or more endoscopies in the first year during attempted cyst eradication. If surveillance is chosen, then it is possible that no further expenses will be incurred until a follow-up imaging study is performed 1 year later.
Potential benefits and risks for pancreatic cyst ablation
Benefits
Decreased malignant potential
Endoscopists routinely perform polypectomy on colon adenomas to arrest their potential neoplastic transformation, and studies have documented that this technique decreases subsequent risk of development and death from colon cancer. A similar but largely unproven rationale underlies the endoscopic therapy for Barrett neoplasia to prevent esophageal cancer. The malignant potential of PCNs, such as MCNs and IPMNs, arise from the cyst epithelial lining. Hence, the destruction of the epithelial lining of PCNs may abate or completely remove the neoplastic potential. However, this hypothesis of the potential benefit of nonoperative therapy for PCNs remains only theoretical.
Decreased costs over time
Surveillance of pancreatic cysts is most commonly performed every 1 to 2 years with imaging studies, such as CT or MRI. However, this surveillance is expensive. If ablation could be documented to be effective and durable, surveillance intervals could theoretically be lengthened or completely stopped. However, the technique of pancreatic cyst ablation is still in its infancy and whether the other still evolving nonoperative surveillance patterns of PCNs can be changed following ablation is still unknown.
Psychological benefit to the patient
In some patients, knowledge that they possess a premalignant cyst can provoke significant anxiety. This anxiety can be augmented if the cyst does not meet the criteria for surgical resection or the patient is not a candidate for surgery because of comorbidities. In these patients, cyst ablation may allay some fears and provide some hope that an attempted intervention is performed for the lesion.
Risks
Complications
Adverse events associated with endoscopic pancreatic cyst ablation may include outcomes from either endoscopy or injection of ablative agents. The incidence and management of these outcomes are discussed subsequently.
Incomplete ablation
During colonoscopy, endoscopic polypectomy may be incomplete and leave residual adenoma. Similarly, ablation of Barrett esophagus may not completely destroy the metaplastic intestinal epithelium. After pancreatic cyst ablation, some epithelium may remain untreated and therefore continue to harbor malignant potential.
High initial treatment costs
If a decision is made to ablate a pancreatic cyst, then there will be increased upfront costs associated with 1 or more endoscopies in the first year during attempted cyst eradication. If surveillance is chosen, then it is possible that no further expenses will be incurred until a follow-up imaging study is performed 1 year later.
Choice of ablative agent
Ethanol
The ideal choice for pancreatic cyst ablation should be cheap, widely available, locally destructive, and easy to use. Many ablative agents, such as acetic acid or tetracycline, have been applied percutaneously or intraoperatively to various anatomic sites, but ethanol is most commonly used. Ethanol is hypothesized to induce cell death by membrane lysis, protein denaturation, and vascular occlusion and has been used for the destruction of solid liver or adrenal tumors as well as cystic lesions of the liver, kidney, thyroid gland, and various other sites. It is therefore not surprising that ethanol was the initial agent used for endoscopic ablation of PCNs. In addition to fulfilling all of the criteria for an ideal choice listed above, ethanol also possesses thin viscosity, which permits easy injection through a 22-gauge needle used in endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA).
Paclitaxel
The only other agent used to date for endoscopic pancreatic cyst ablation is paclitaxel. Paclitaxel is a hydrophobic, viscous chemotherapeutic agent that inhibits cell processes that are dependent on microtubule turnover.
How to perform pancreatic cyst ablation
Linear Endosonography
The advent of linear endoscopic ultrasound (EUS) transformed EUS from a purely diagnostic to also a therapeutic technique. Linear EUS permits EUS-FNA by placement of a needle into various anatomic sites to sample tumors or lymph nodes. EUS-FNA may also aspirate and drain pancreatic cysts and other fluid collections. Because of the close apposition between the endoscope and the pancreas, EUS is an ideal minimally invasive technique for guiding therapeutic interventions, such as pseudocyst drainage, tissue ablation, and cyst ablation in the pancreas. Endosonographers desiring to perform pancreatic tumor ablation should be competent in all aspects of EUS-FNA.
Technique
All studies to date describing EUS-guided pancreatic cyst ablation have used a 22-gauge needle. The safety of any 19-gauge needle or 20-gauge celiac neurolysis needle (Cook Medical, Inc., Winston-Salem, NC, USA) for this technique has not been evaluated. Therefore these 2 needles are not recommended for use at present. Use of a stylet before cyst ablation is not essential. After transgastric or transduodenal passage of a 22-gauge FNA needle into a cyst, a syringe is attached to the proximal end of the needle and near-complete evacuation of the cyst should be attempted. If fluid is present within the syringe, it may be used for cyst analysis if required. The amount of aspirated fluid, the viscosity, and the color should be noted. To ensure that the cyst is not completely collapsed, the needle remains within the cyst before injection of the ablative agent. If the cyst fluid is viscous, it may not be possible to evacuate the cyst contents as much as desired. Hence, 0.5 to 1.0 mL of saline is injected into the cyst to decrease the viscosity of cyst fluid or expand the small cyst cavity to confirm proper needle placement. With the needle in the nearly collapsed cyst, ethanol is injected in the cyst using a volume equal to that initially aspirated from the cyst. If the cyst fluid is not viscous and 3 to 4 mL is aspirated, then an equal volume of alcohol (3–4 mL) of ethanol is used in the initial injection. Studies to date have performed cyst lavage for 5 minutes, alternately filling and emptying the cavity. For cysts with viscous fluid, this is performed as 3 to 4 lavages over the 5-minute period. When cyst fluid is thin then 7 to 8 lavages are done over the same period. At the conclusion of the lavage, the ethanol-cyst fluid mixture should be completely drained of fluid as much as possible. When used, paclitaxel is injected into the cyst after alcohol lavage and left in place.
Cysts considered eligible for ablation
Size
In published studies, the treated cysts are usually suspected clinically as mucinous cysts (ie, MCNs and IPMNs) that measure between 1 and 6 cm in maximal diameter ( Table 1 ). Macrocystic (diameter >2 cm) serous cysts have also been ablated; however, these should generally be avoided because of their very low malignant potential. Intentional treatment of other pancreatic cysts such as neuroendocrine tumors or lymphoepithelial cysts has not been reported.
| References | Design | N | Lavage Used | Median size, mm (range) | Septations | Cyst Location Head Body/Tail | Clinical Diagnosis | |
|---|---|---|---|---|---|---|---|---|
| Gan et al, 2005 | Prospective, Cohort | 25 | Increasing concentrations of ethanol | 19.4 (6–30) | Second half of study | 32% | 68% | MCN 52% IPMN 16% Indeterminate 32% |
| Oh et al, 2008 | Prospective, Cohort | 14 | Ethanol and Paclitaxel | 25.5 (17–52) | Not stated | 7.1% | 92.9% | MCN 52% IPMN 16% Indeterminate 32% |
| Oh et al, 2009 a | Prospective, Cohort | 10 | Ethanol and Paclitaxel | 29.5 (20–68) | All patients | 40% | 60% | MCN 30% IPMN 0% Indeterminate 70% |
| DeWitt et al, 2009 | Prospective, DBRCT | 42 | Saline vs Ethanol | 22.4 (10–58) | ≤5 | 81% | 19% | MCN 41% IPMN 41% Indeterminate 18% |
| Oh et al, 2011 b | Prospective, Cohort | 52 | Ethanol and Paclitaxel | 31.8 (17–68) | 1–5 | 31% | 69% | MCN 17% SCA 19% PC 4% Indeterminate 50% |
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Endoscopic Ultrasound: Contrast Enhancement
Endoscopic Ultrasonography-Guided Tumor Ablation
Endoscopic Ultrasonography-Guided Pancreatic Drainage
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