The Role of Endoscopic Ultrasound in the Interventional Management of Mediastinal Collections: A Narrative Review

The numerous causes underlying mediastinal lesions require different diagnostic and therapeutic approaches, including conservative, minimally invasive, and surgical interventions. Solid lesions of a malignant nature, mostly located in the anterior mediastinum, are properly treated with surgical resection either with or without adjuvant schemes. In contrast, a surveillance program is usually recommended with solid benign tumors, depending on their size and related symptomatology. In the management of mediastinal collections, when a drainage intervention is required (suspicion of infection and symptomatology), a minimally invasive nonsurgical procedure or thoracic surgery is considered. The minimally invasive nonsurgical procedures that can be available are percutaneous radiology-guided imaging (abdominal ultrasound (US) or computed tomography (CT) scan), complete single-aspiration guided by endoscopic ultrasound (EUS) or endobronchial ultrasound (EBUS), and transmural drainage guided by EUS. Surgical debridement is feasible to treat collections, but as this entails considerable risk of postoperative complications, it is chosen only when other minimally invasive therapies are not possible. The published literature related to the interventional endoscopic approach to mediastinal lesions is scarce. Nevertheless, reports in this field reveal that interventional EUS may have a role in both the diagnosis of and therapeutic approach to mediastinal lesions, mainly in the management of mediastinal collections.


Introduction And Background
Mediastinal lesions include a broad spectrum of pathologies. According to their nature, they may complicate locally with a mass effect on adjacent organs [1]. These lesions are divided into primary (e.g., solid or cystic lesions) and secondary (e.g., infectious, inflammatory, or hemorrhagic lesions) [2]. Multiple treatment options for mediastinal lesions exist, such as conservative management, minimally invasive procedures, and surgical interventions. Endoscopic ultrasound (EUS) is in most cases limited to posterior mediastinumlocated lesions, offering an interventional ability to obtain diagnostic samples of mediastinal lesions.
The management of mediastinal collections that require drainage includes a surgical approach or a minimally invasive nonsurgical procedure such as percutaneously guided imaging or endoscopically by EUS.
The main objective of this review is to highlight the management of mediastinal collections (mainly posterior or middle) with simple (single aspiration) (safer but higher relapse rate) or transmural drainage (stenting) (high efficiency but more aggressive) guided by EUS.

Review Methodology
We conducted a traditional narrative review (non-systematic and not including all available evidence) for obtaining a broad perspective on this topic. The main purpose was to identify peer-reviewed, published studies evaluating the role of interventional EUS in the management of mediastinal collections.
The literature cited in this narrative review was published from 1973 to 2022 and was searched on PubMed and Google Scholar. The following keywords were used: "mediastinal collection," "mediastinal cyst," "mediastinal pseudocyst," "endoscopic ultrasound," "fine needle aspiration," and "transmural drainage." The reviewers selected these articles by reviewing their titles and abstracts. Eligible studies considered relevant for drafting this narrative review included those that evaluated mediastinal collections or mediastinal pseudocyst treated by endoscopic ultrasound guidance (single aspiration, drainage, or pancreatic stent in the case of mediastinal pseudocyst). Additionally, the reference lists of the included studies were handsearched.

Classification of mediastinal lesions
The mediastinum is a division of the thoracic cavity that has two main compartments: superior and inferior. The inferior is the larger one and so is further subdivided into three compartments: anterior, middle, and posterior [3].
This division accurately accounts for localizing and characterizing mediastinal lesions. Firstly, the mediastinum is divided into superior and inferior compartments by a plane that runs from the sternal angle to the T4-T5 vertebrae. The superior mediastinum is limited by the root of the neck at the top of the first ribs and by the inferior mediastinum below the described transverse thoracic plane. Secondly, the inferior mediastinum is divided into the anterior, middle, and posterior mediastinum, as shown in Figure 1.

FIGURE 1: Compartments of the mediastinum
The two main compartments are the superior and inferior mediastinum (including anterior, middle, and posterior). The location of the trachea and esophagus is essential for understanding the role and limitations of EBUS and EUS, respectively.  Mediastinal lesions are clustered according to their tumor or cystic formation as malignant or benign course and primary or secondary origin. Following this classification, we may carry out differential diagnoses and identify potential treatment approaches. Table 2, Table 3, and Table 4 include most of the mediastinal lesions, arranged according to their locations [1,.

Mediastinal collections in the posterior mediastinum
Lesions located in the posterior mediastinum are most commonly punctured or treated by EUS. As previously commented, most of these lesions are abscesses and pancreatic fluid collections (pseudocyst or rarely walled-off pancreatic necrosis).

Mediastinal Abscess
A mediastinal abscess can be fatal, with mortality rates reaching 40%, especially when proper diagnosis and treatment are delayed [4]. Injury of adjacent organs such as esophageal perforation, sternal osteomyelitis, and extension of pulmonary, pleural, cervical, or retroperitoneal infection are the primary causes of associated morbimortality. Classically, antibiotic therapy in combination with surgical debridement, either by open surgery or video-assisted, is the treatment of choice [5]. Nevertheless, minimally invasive procedures, such as percutaneous drainage, have proven effective, and they carry lower complication rates [6].

Pancreatic Fluid Collections
Pancreatic fluid collections, mainly pseudocysts, are the second cause of secondary mediastinal lesions. They develop by encapsulation with an inflammatory tissue wall, which appears in the background of acute or chronic pancreatitis. Due to the location of the pancreas, the pancreatic fluid collection grows throughout the retroperitoneal region; however, it may be allocated in other cavities such as the mediastinum. The lesion reaches the mediastinum typically through the diaphragmatic hiatus and less commonly via the aorta or inferior cava hiatus vein. Most pancreatic fluid collections resolve spontaneously [7]. In accordance with lesion features such as size, related symptom severity, pancreatic ductal anatomy, and operator experience, the need for therapy will be discussed below.

Diagnostic and Interventional Imaging
It appears that a CT scan is equal to or slightly superior to magnetic resonance imaging (MRI) in the diagnosis of anterior mediastinal tumors, except for thymic cysts. Some studies analyzing and comparing the sensitivity of CT scan images to MRI in mediastinum lesion diagnosis reported only a slight superiority of CT scan, with an accuracy of 61% compared to 56%. They optimized the diagnosis, putting the two together and reaching 67% accuracy [8]. However, MRI benefits were the focus of the study of cystic lesions since it is capable of identifying malignancy signs, such as solid components, and areas of necrosis, and also explicitly distinguishing thymus hyperplasia from thymus neoplasia [8].
Transthoracic ultrasound (US) has proven its utility in the study of mediastinal lesions since it offers the advantage of sampling via US-guided fine needle aspiration (US-FNA). Nevertheless, the benefits are limited to the anterior mediastinum [9].

Interventional Diagnosis by EBUS
Mediastinal lesion samples obtained by either EBUS-guided transbronchial needle aspiration (TBNA) or endoscopic ultrasound-guided tissue acquisition (EUS-TA) show an average sensitivity of 93%, a result that is notably valuable regarding lymphoma and other mediastinal neoplastic studies since diagnosis requires immunohistochemical evidence [10]. These are minimally invasive procedures that permit the avoidance of more aggressive interventions such as mediastinoscopy and thoracoscopy and thereby offer a lower complication rate [11]. In addition, it is important to consider anatomical references to better understand the range of intervention capacity for each procedure. Thus, EBUS-TBNA is performed with a bronchoscope using a transducer on the tip, which enables approaching the peribronchial or peritracheal areas to either sample tissue or drain aspiration. Furthermore, lesions located in the anterior mediastinum are still not accessible by EBUS-TBNA.

Interventional Diagnosis by EUS of Middle and Posterior Mediastinal Lesions
EUS-TA offers the power to acquire tissue from the middle and posterior mediastinum along the esophagus for cytohistological study with significant accuracy and safety [12,13,18,[39][40][41][42][43][44][45]. A study that compared the usefulness of EBUS-TBNA versus EUS-FNA in the diagnosis of mediastinal lesions under suspicion of malignancy did not uncover differences between the two procedures, and by combining them, researchers achieved nearly 100% accuracy [12]. These results suggest the utility of combining the two procedures to inspect and sample within the different mediastinum regions.
In contrast, although they are both considered minimally invasive interventions compared to the classically used methods such as mediastinoscopy, there could still be complications. A national retrospective survey evaluated the rate of adverse events related to EBUS-TBNA and EUS-FNA. For a 12-year period, the study obtained an adverse event rate of 0.11% and 0.16% related to EBUS-TBNA and EUS-FNA, respectively, and found an overall mortality rate of 0.04% [13]. Most complications were infectious diseases related to tissue acquisition; bleeding was less frequent and better controlled during procedures. A technical advantage of EUS-TA also includes the capability of using a wider-diameter needle such as 19-gauge needles [14].

Conservative Management Strategy
Conservative treatment is considered the first step of therapy only if the patient is suitable for this approach. This involves the lesion type and its clinical impact. Mediastinal collections such as pancreatic pseudocyst can be handled by diverse approaches. Case reports have shown the efficacy of conservative treatment with octreotide, a somatostatin analog that inhibits pancreatic secretions and facilitates the closing of the pancreatic fistula, which forms the collection [15][16][17]. Nonetheless, the evidence for clinical recommendation of the treatment is lacking. On the other hand, mediastinal abscess shows a poor response to conservative treatment. Therefore, a better approach would be surgical drainage and then minimally interventional procedures.

Interventionist Treatment
Patients who are nonresponders to conservative treatment of lesions are considered for therapeutic intervention, aiming at debridement and/or drainage. In this setting and because of overall morbidity especially in nonsurgical candidates, minimally invasive techniques have been offered and have shown satisfactory results. These techniques include CT-guided percutaneous drainage, EUS-or EBUS-guided single needle aspiration, and/or EUS-guided transmural drainage. Decisions on strategy therapy should be made by a multidisciplinary committee. The use of C02 is highly recommended for EUS-guided transmural procedures to prevent air embolism.

CT-Guided Percutaneous Drainage
CT-guided percutaneous drainage represents an appropriate alternative to interventionist treatment. Since the first report in 1987 of a mediastinal abscess treated by CT-guided percutaneous drainage, several case reports and a 10-year series including 23 patients have been published [6,[25][26][27][28]. Some 84% of abscesses were located in the posterior mediastinum, while the remainder were located in the anterior mediastinum. Technical success was achieved in 100% of procedures, while clinical success, which was defined as abscess resolution by a percutaneous approach without the need for surgical debridement, was achieved in 22 of 23 patients (96%) [6]. However, studies comparing this procedure to surgical debridement and endoscopic management are lacking.

EBUS-TBNA Drainage (Single Aspiration)
There are a few data concerning treatment using the EBUS-TBNA approach. Table 5 summarizes case reports of successful EBUS-TBNA treatment [36,[46][47][48][49][50][51][52][53]. These reports suggest that EBUS-TBNA could be a safe alternative treatment compared to more aggressive strategies. The limitations of this approach include the use of narrow devices such as 22-or 25-gauge needles, which preclude performing drainage by single aspiration only. Furthermore, as previously mentioned, mediastinal access to the EBUS-TBNA is limited, so almost all reported cases listed involve lesions located in the paratracheal area within the middle mediastinum.
Author, year

EUS-Guided Drainage (Single Aspiration and Transmural Drainage)
Several factors may influence the feasibility of endoscopic treatment in the mediastinal region. The tubular shape of the esophagus and the elastic property of the GI wall combined allow the endoscope tip to get closer to a remote anatomical region. Additionally, therapeutic scopes are provided with wider working channels so that a broader spectrum of devices is enabled, thereby allowing several alternative strategies to be considered. Mediastinal collections treated by EUS guidance are located in the posterior or middle (or paraesophageal) mediastinum. The esophagus is located at the posterior pole of the middle mediastinum, so access is confined to anterior paraesophageal structures corresponding to the middle mediastinum and posterior mediastinum region. The anterior mediastinum is limited by vascular structures and trachea and is far away from the esophagus, so these regions are best approached by other techniques. Several variables such as lesion features (size and solid component) and the clinical scenario (fever and sepsis) are taken into consideration when deciding upon the best strategy via EUS.

EUS-Guided Single Aspiration
EUS-guided single aspiration is defined as a needle puncture followed by total or near-total content aspiration to collapse the lesion volume; these steps allow for shortening the procedure duration in a safe way. This simple interventional approach is documented in several reports showing acceptable efficacy, reducing the risk of procedure complications compared to transmural drainage. However, the likelihood of recurrence on follow-up is real [18][19][20][21].   Although EUS-guided single aspiration represents a lower part of the series, it may offer benefits such as endoscopic drainage and obtaining a sample for culture at the same time. The strengths of this option are that it does not need great technical skill and it is less risky than transmural drainage. Moreover, if clinical outcomes are favorable, no further endoscopy is needed.

EUS-Guided Transmural Drainage
This approach is based on temporary stent (plastic or metal) placement to maintain proper drainage between the two cavities, the lesion, and the digestive lumen. EUS-guided transmural drainage of a mediastinal collection is the most common endoscopic treatment approach since its efficacy is well recognized in other body regions as well, such as the abdomen.  It has shown good results in abdominal lesions; in addition, it is considered the treatment of choice for abdominal lesion drainage in peripancreatic collections. This strategy directed to mediastinal lesions appeals to the abovementioned experience (EUS-guided transesophageal drainage), and the outcomes are acceptable. It seems that the presence of an abscess, likely in the form of a heterogeneous and solid-content lesion, induced the need to perform transmural drainage and, eventually, the creation of a stoma. Although these are case reports, a highlight is a German study that included 15 patients with paraesophageal abscesses treated by EUS-guided transmural technique, with the creation of esophagostomy and routine endoscopic washing, and achieving clinical success in all the patients included [22].
Given the low-level experience reported, it is difficult to recommend a specific stent; however, the majority of cases described involved plastic single-or double-pigtail stent use, likely to avoid local complications related to the use of self-expandable metal stents [23].
Regarding the safety of EUS-guided transmural drainage, two adverse events were reported. One was pneumothorax while performing transesophageal puncture, which was controlled during the procedure [24] The other was a pulmonary artery embolism unrelated to the technique the day after the procedure, with a fatal outcome [22].
EUS-guided transmural drainage is not only effective for lesions originating in the mediastinum; there is also evidence of mediastinum-extended abdominal lesions successfully treated using transmural EUS guidance.  The main etiology of the lesions was pancreatic pseudocyst, which, as noted above, constitutes a minor but feasible extension. The endoscopic strategy is diverse, with the EUS-guided drainage being the most common approach. Other strategies include transpapillary pancreatic treatment and EUS-guided single aspiration. Clinical outcomes are promising for such an uncommon condition, as is the safety profile. Pneumothorax was reported while placing a lumen-apposing stent that was successfully treated by intercostal drainage. In spite of this, the thoracic surgeon who performed the procedure thought this was a complication from orotracheal positive pressure [24,54,61].

FIGURE 2: Transmural drainage of mediastinal collection
A: Computed tomography scan image of an infected mediastinal collection (note the air-fluid level, yellow arrow). B: Image of endosonography-guided transmural drainage of a mediastinal abscess (yellow arrow); EUS-guided aspiration using a 19 G needle (green arrow) was performed to obtain a sample. C: Endoscopic view of the transesophageal drainage of a mediastinal lesion by placing a lumen-apposing stent (white arrow). D: Computed tomography image of a lumen-apposing stent placed for mediastinal collection of transesophageal drainage (white arrow).

Surgical Approach
Mediastinal surgery constitutes the treatment of abscesses within the mediastinum with the highest success rate. Moreover, since the 1990s, the surgical approach has had new technologies based on video images available, allowing less invasive access compared to open surgery, with a similar recurrence rate [29]. Although these procedures are now less aggressive than conventional approaches, they carry a surgical and anesthesia-related morbidity risk.

Conclusions
The management of mediastinal collections in which a drainage is required includes a surgical approach and minimally invasive nonsurgical procedures such as percutaneously guided imaging and interventional endoscopy. The nature and location of the collection will condition the selection of the strategy.
Furthermore, although scientific evidence of EUS-guided therapy is limited, it is a promising, minimally invasive technique. The most common mediastinal collections treated by EUS are abscesses and pseudocyst (migrated to the mediastinum) located in the posterior compartment. Basically, EUS-guided drainage of mediastinal collections includes two techniques: collapse by single aspiration (no stent) and transmural drainage (with stent deployment).
Single aspiration can be used by EBUS or EUS, depending on the collection site and accessibility. This is a well-acceptable, non-risky technique, but the potential relapse rate may be higher.
A EUS-guided transmural (transesophageal) drainage differs because of the necessity of stenting, using plastic stents or LAMS. Despite it being more aggressive and associated with complications, the outcomes in long term are superior.
Decisions on therapy strategy should be made by a multidisciplinary committee including surgeons, radiologists, and endoscopists.

Conflicts of interest:
In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.