The management of PCs has been a topic of debate for many years. The management approach depends on many factors but mainly on the type and size of the cyst, as it may reflect its malignancy potential. The use of EUS to ablate these lesions has been an ongoing area of research. Our analysis showed that EUS-PCA is an effective and safe way of managing PCs.
Typical EUS-PCA includes careful assessment of the PCs, including location, size, and presence of high-risk stigmata or worrisome features, followed by cyst fluid aspiration, and injection of chemicals into the cyst. [13] The most used chemical is alcohol due to its ability to cause tissue necrosis from direct coagulation, sclerosis of the tissue in contact, denaturation of proteins, and dehydration of the epithelial cells [21, 28]. Adding chemotherapeutic agents, such as paclitaxel and gemcitabine, to ethanol injection has improved cyst resolution [13, 14, 16]. Lauromacrogol, a sclerosing agent, is an emerging alternative to alcohol and chemotherapeutic agents [15].
In the present meta-analysis, we sought to determine the effectiveness of EUS-PCA in managing pancreatic cystic neoplasms. A total of 438 patients with pancreatic cysts were included in the study, with the majority classified as indeterminate (n = 189) or mucinous (n = 170). The anatomical distribution of cysts revealed a predominance in the pancreatic body, followed by the head and then the tail. The combined analysis of the studies included in our review revealed that EUS-PCA exhibits substantial effectiveness in the treatment of pancreatic cystic neoplasms, leading to cyst resolution in nearly 80% of cases (comprising 50% complete resolution and 27% partial resolution). Moreover, subgroup analysis suggests that EUS ablation permits a higher degree of complete resolution of pancreatic cysts larger than 2 cm, and when using a chemotherapeutic agent. These findings suggest that EUS-PCA represents a promising therapeutic option for patients with pancreatic cystic neoplasms, with potential benefits in reducing the risk of malignant transformation and improving patient outcomes.
Our analysis also provided evidence supporting the safety of EUS-PCA, with only a few major complications observed among the included patients. Acute pancreatitis was reported in 3% of patients, while one patient experienced a small bowel perforation, and two patients exhibited peri-cystic spillage and chemical peritonitis. The occurrence of acute pancreatitis may be attributed to the activation of zymogens as a result of the cytotoxic effects of the chemicals employed during the procedure on the exposed main pancreatic duct [21, 29]. The findings are in contrast to pancreatic surgery, which has a morbidity rate higher than 40% and a mortality rate reaching 20% [9, 30].
EUS-PCA is a valuable alternative for patients who are deemed unsuitable for surgical intervention. Nevertheless, it is imperative to note that EUS ablation is not a suitable treatment for all types of cysts [10, 31, 32]. In 2019, an international position statement on EUS-guided PC ablation recommended chemoablation for surgically fit patients with an anticipated reasonable life expectancy, confirmed diagnosis of a mucinous pancreatic cyst that is 2 cm and enlarging or at least 3 centimeters in diameter [10, 32]. Nevertheless, the group did not reach a consensus on absolute indications or contraindications for EUS-PCA. Therefore, a patient-centered approach regarding EUS ablation should consider a multidisciplinary discussion of individual circumstances and thoroughly assess the potential risks and benefits of the procedure.
We utilized the modified Downs and Black checklist to assess the risk of bias in the studies included in our analysis. The results indicated variations in the overall quality of the studies, with some demonstrating a higher degree of bias risk than others. While the reporting domain was generally well-addressed, certain aspects, such as bias and confounding, displayed weaknesses. Additionally, an important finding was the frequent lack of attention or insufficient consideration of external validity in the included studies. This aspect warrants particular attention in future research, as it may significantly impact the generalizability of findings in similar studies.
A primary obstacle in the implementation of EUS-PCA is the accessibility and precision in targeting pancreatic cysts. This is especially pronounced when dealing with small or hard-to-reach cysts in the tail or inferior pancreatic head. Furthermore, the use of ethanol as an ablative agent may be difficult due to trouble achieving optimal intracystic ethanol concentration [20] and potentially less efficacious in cysts with thick septations, adjacent masses, and nodules [18]. Newer agents such as lauromacrogol, which is usually used as sclerotherapy for varicose veins, are being explored as a possible ablation agent and have shown promising results with fewer side effects [25]. These limitations underscore the importance of careful patient selection, as well as skilled technical expertise, when utilizing EUS-PCA as a therapeutic option for pancreatic cystic neoplasms.
All studies included in this meta-analysis were prospective where patients were followed for at least 12 months after the procedure. All studies reported positive outcomes except for Gómez et al. [20]. They explained that the results could be due to low final ethanol concentrations; however, final ethanol concentrations close to 80% were achieved in some participants, and no correlation with therapy response was found [20].
This meta-analysis has several limitations that warrant consideration. Notably, there was significant heterogeneity in the techniques employed across the included studies, potentially introducing inconsistencies in treatment outcomes. Another limitation of our study is the variation in defining primary outcomes across included studies. While most used the same volume percentages, three studies had different criteria, such as the absence of visible cysts. Additionally, not all studies reported complications in a standardized manner, raising concerns about the accuracy of reported incidence rates, particularly due to the lack of an evidence-based adverse events grading system. Moreover, the emphasis on short-term outcomes, particularly due to the limited availability of long-term data, may lead to an overestimation of the treatment's effectiveness, as negative outcomes from PCs are often seen over the long term. However, one study with a 69-month follow-up period showed positive effects [17], These promising results indicate the need for further studies assessing potential long-term benefits. Consequently, these limitations should be acknowledged when interpreting the meta-analytic findings and applying them in clinical practice.
In light of the identified limitations, further research is required to fully assess the safety and efficacy of EUS-PCA and enhance its adoption for the treatment of pancreatic cysts. Specifically, prospective controlled randomized trials are needed to provide robust and conclusive evidence to support the use of this technique. Moreover, comparative studies evaluating the effectiveness of EUS-PCA against surgical excision of pancreatic cysts could offer valuable insights into the benefits and limitations of each approach. Such studies may elucidate the specific indications and optimal treatment strategies for each modality, facilitating the appropriate selection based on patient and lesion characteristics. Ultimately, these efforts may help to establish EUS-PCA as a widely accepted, safe, and effective therapeutic option for the management of pancreatic cystic lesions.