With advances in endoscopic technologies, endoscopic clips have been used widely and successfully in the treatment of various types of oesophageal perforations, anastomosis leakages and fistulas. Our aim was to summarize the experience with two types of clips: The through-the-scope (TTS) clip and the over-the-scope clip (OTSC). We summarized the results of oesophageal perforation closure with endoscopic clips. We processed the data from 38 articles and 127 patients using PubMed search. Based on evidence thus far, it can be stated that both clips can be used in the treatment of early (< 24 h), iatrogenic, spontaneous oesophageal perforations in the case of limited injury or contamination. TTS clips are efficacious in the treatment of 10 mm lesions, while bigger (< 20 mm) lesions can be treated successfully with OTSC clips, whose effectiveness is similar to that of surgical treatment. However, the clinical success rate is significantly lower in the case of fistulas and in the treatment of anastomosis insufficiency. Tough prospective randomized multicentre trials, which produce the largest amount of evidence, are still missing. Based on experience so far, endoscopic clips represent a possible therapeutic alternative to surgery in the treatment of oesophageal perforations under well-defined conditions.

Despite remarkable advances in surgery and intensive care, oesophageal perforation is still a life-threatening condition[1,2]. It is iatrogenic (caused by a device) in a majority of cases; perforation caused by a foreign body or trauma and spontaneous perforation are less frequent. Several well-known factors influence its course: location and cause of perforation, time from diagnosis until care, co-morbidities of the oesophagus, general condition of the patient and selected treatment[3,4]. In addition to oesophageal perforation, suture insufficiency of the oesophagus and other oesophageal fistulas also pose serious therapeutic challenges nowadays.

With the development of endoscopic technology during the last two decades, endoscopic clips and self-expanding stents have been used successfully and ever more widely in the treatment of oesophageal perforations/fistulas of various origins[5,6]. Oesophageal injury was first closed endoscopically with the placement of clips in 1995; the injury had occurred as a consequence of pneumatic dilatation in a patient with achalasia[7]. Since then, this method has been used for oesophageal perforations of various aetiologies, including Boerhaave syndrome[8-11]. To date, the method has been successful, especially in the treatment of small (< 2 cm) injuries. The following review article describes indications of endoscopy and endoscopic clips in the treatment of oesophageal perforation.

Essential elements in the treatment of oesophageal perforation include resolving the source of the infection, operative or non-operative closure of the defect, and thoracic and mediastinal debridement. Important parts of therapy are controlling sepsis, intensive monitoring, targeted antibiotic/antimycotic treatment, fluid therapy and strengthening the immune system of the body with enteral nutrition.

Several obvious factors determine treatment strategy and prognosis: (1) time of the diagnosis (delay); (2) localization of the perforation; (3) severity and size of the perforation; (4) presence of septic complications, physiologic reserves of the patient and existing co-morbidity of the oesophagus; and (5) the experience of the professionals providing care.

Primary closure of the oesophagus is successful in more than 90% of cases if the defect is closed within 24 h and there were no co-morbidities in the oesophagus (tumour, stricture, etc.)[25,26]. In this phase, tissues are not oedematic and are easy to suture/close; in addition, there is no active bacterial infection in the thoracic cavity and/or mediastinum. If the perforation occurred more than 24 h beforehand, the prognosis is significantly reduced due to rapidly developing septic complications and less successful surgical/conservative treatment[12,27].

It is well-known that thoracic transmural injuries of the oesophagus have the worst prognosis due to rapidly developing mediastinitis and sepsis, followed by injury of the abdominal segment, while perforation in the cervical segment has the best prognosis.

Intramural injuries usually respond well to conservative treatment. Transmural and transpleural injuries represent the worst defects. Treatment strategy is also essentially influenced by the size of the defect. These factors are especially important in using the endoscopic technique (see below).

General stress tolerance of the patient, existing co-morbidities and severe septic condition are known to worsen the prognosis[12,27]. Existing co-morbidities of the oesophagus are especially important in selecting a treatment option, but may also influence the prognosis significantly (such as tumorous perforation).

Today, it is only possible to manage oesophageal perforations with multidisciplinary co-operation. The role of a surgeon experienced in the treatment of perforations and that of a gastroenterologist familiar with new innovative endoscopic techniques are decisive. Treatment has to be administered individually with an understanding of the general principles involved.

Endoscopic procedures representing a minimal or significantly lower burden are more widely used not only in the diagnosis of oesophageal perforation, but also in its treatment. A number of publications, especially case histories, demonstrate the successful use of endoscopic clips and self-expanding stents in the treatment of oesophageal injuries[5,28]. The applicability of endoscopic methods has also been confirmed in experimental animal models (endoscopic clipping vs suturing vs thoracoscopic repair)[29]. Endoscopic clipping basically results in the immediate resolution of the oesophageal defect, while various types of stents aid in resolving extravasation from the oesophagus (diversion of enteral contents) and provide further slow healing of the injury. Stent implantation is mainly used in the treatment of large (> 2.5-3 cm) injuries of the middle and lower third segments of the oesophagus, and is especially suitable for the treatment of tumorous perforations where dysphagia is also resolved. Several types of stents are known, such as self-expanding plastic stents and fully and partially covered, self-expanding metal stents. In the case of injuries of the gastro-oesophageal junction, a partially covered stent is recommended with the smallest migration tendency if there is no oesophageal stricture[30]. The success of the procedure also depends on early application. Any delay in endoscopic treatment significantly reduces the chances of healing of the oesophageal perforation, as is the case with other treatment options[5]. According to the latest systematic review, the overall technical and clinical success rates of oesophageal stent placement in patient groups were 91% and 81%, respectively, and mortality was also acceptably low at 13%[31]. One of the most common complications of stent implantation is stent migration, which occurs in 20.8% of cases; this percentage is lower (11%) in the case of metal stents and higher for plastic stents (27%)[31]. However, stent migration may be reduced significantly with clips (proximal clip fixation[32]).

Endoscopic clips have been used in the treatment of oesophageal perforation for 20 years; however, the number of publications on their use has only increased during the last few years. Generally, experience is available with two types of clip: the through-the-scope (TTS) clip and the over-the-scope clip (OTSC). TTS clips were developed for haemostasis and the treatment of mucosal ruptures. However, they may only be used in treating small (< 10 mm) injuries due to their limited (< 11 mm) wingspan.

The wingspan of the OTSC (OVESCO Endoscopy, Tübingen, Germany) is not significantly larger (11-14 mm), but the system also features a special applicator cap[38]. The entire thickness of the tissue may be pulled into the cap by suction and/or with graspers, and the tissue may be united with special clamps (a bear claw). Experience shows that this innovative clipping device made of biocompatible nitinol also provides stronger closure of large (1-2 cm) defects[39]. Nowadays, several types of clips are available (blunt/atraumatic and pointed-teeth/traumatic). There is also a special “anchor” which aids in the closure of fibrotic fistulas. It only takes an experienced endoscopic professional a few minutes to close a defect[40]. One iatrogenic oesophageal injury has been reported with the use of this device when an endoscopic OTSC was inserted[40]; the injury may have been caused by the 2 mm rim of the plastic cap. However, experience shows that the device can be used safely, and the complication rate is around 1%[40,41].

Tables 1 and 2 summarize the results of the PubMed (Medline) search.

Open in New Tab   Full Size Figure   Download Figure

Figure 1 Algorithm for the management of oesophageal perforations.

We used the following key words: Oesophageal perforation, gastrointestinal perforation, endoscopic clip (ping) and OTSC (latest search date: 15 March 2015). We processed the data from 38 articles and 127 patients. We placed causes of perforation into three categories in the table: Perforation was defined as an acute iatrogenic or spontaneous defect, leak as an insufficiency/disruption of a surgical anastomosis, and fistula as a chronic residual inflammatory communication between the oesophagus, with a mediastinal or pleural space or tracheobronchial tract under the skin.

Statistical analysis: Categorical data were analyzed using χ² and Fisher’s exact test [SPSS version 15.0 (© 2007 SPSS Inc.)].

Most publications are case reports or retrospective analyses with heterogeneous indications. The number of publications significantly increased after the first clinical use of the OTSC clip in 2007, first in Europe and then in the United States and other countries as well. Neither randomized nor comparative (TTS vs OTSC) studies have been conducted with the use of clips. One prospective European multicentre study and two retrospective North American multicentre studies have been published on the use of OTSC clips in the treatment of GI perforations[40-42]. Unfortunately, salient information is missing from numerous articles, and generally there are no reports on the follow-up period at all.

Based on the results, it can be concluded that both clips are suitable for the treatment and early management (< 24 h) of iatrogenic, spontaneous oesophageal perforation in the case of limited injury and contamination. TTS clips are successfully used for injuries of an average of 10 mm, while OTSC clips may also be successful in the treatment of larger injuries. More clips may also be used to close a defect, and various clips may be combined[40,43]; in addition, closure with a clip may be repeated[44]. In accordance with the latest recommendations from the European Society of Gastrointestinal Endoscopy[30], clips may only be used in the treatment of an injury in the case of safe care, in stable patients, with a clear oesophagus, limited mediastinal contamination and limited injury (intramural/transmural). Certain immediately diagnosed iatrogenic perforations meet this criterion system in particular. If the amount of mediastinal and/or pleural fluid is more significant, mediastinal and/or pleural space drainage/VATS treatment usually cannot be avoided. The treatment algorithm is summarized in Figure 1.

Based on our analysis (Tables 1 and 2), clips were used early (immediate diagnosis, < 24 h), especially in the case of minimally contaminated iatrogenic injuries or spontaneous ruptures, and the success of healing was similar to that of surgical treatment [TTS 88.8% (24/27); OTSC 92.86% (26/28)]. Although TTS and OTSC clips were used for injuries of varying sizes, their success rates did not diverge significantly (88.8% vs 92.85%, P > 0.12). Of further interest, clips were used with a similar success rate for the far smaller number of perforations of > 24 h which are only associated with a well-defined mediastinal inflammation/abscess [TTS 100% (8/8) vs OTSC 83.3% (5/6)]. Transoesophageal lavage of the process or even vacuum therapy may be of great aid in resolving the abscessing mediastinal process[45].

In selected cases of Boerhaave syndrome, closing the oesophageal injury with endoscopic clips might also be successful. TTS clips were used in two cases. In one patient, a minimal transmural oesophageal injury was diagnosed (a little air in the mediastinum), only the mucosal injury was partially closed with endoscopy, and conservative treatment was administered[46]. In another patient, a 5-7 mm transpleural injury was closed with 3 TTS clips, and additional thoracic drainage and enteral nutrition were administered[47]. In three additional cases, OTSC clips were used successfully to close a spontaneous transmural injury[43,48,49]. In the two matured (> 24 h) perforations, additional VATS therapy was necessary. Similarly, only limited cases have been reported on the treatment of injuries caused by foreign bodies[50,51].

Broad-spectrum antibiotic therapy and suspension of oral nutrition are required in addition to successful early endoscopic care. In the majority of cases, complication-free healing can be expected with careful indication. However, close monitoring of the patient and additional therapy such as mediastinal/pleural drainage or even surgical treatment, if necessary, are also essential.

Fistulizing chronic injuries and treating anastomosis insufficiencies represent a separate group. Experience shows that OTSC clips have provided relatively secure closure so far, but the success rate in acute cases [OTSC 57.7% (15/26) vs TTS 100% (4/4) (P < 0.05) for fistulas; OTSC 77.7% (12/18) vs TTS 54.5% (6/11) (P < 0.05) for leaks] differed significantly in the groups.

Closure is technically often unfeasible, especially in the case of fibrotizing, scarred fistulas and a severely inflamed environment[52]. Most problems stem from insufficiency of the oesophageal anastomosis diagnosed in the early postoperative state. These cases are usually subacute, the tissues are extremely fragile, often ischaemic, and therefore the tendency to heal is already decreased[53]. The success rate for the closure of chronic fistulas is also reduced by previous radiation therapy. If a TTS clip is used, argon plasma coagulation and other mechanical freshening up (with a cytology brush) may aid in stabilizing the clip. These extra manoeuvres may only increase tissue oedema and the success of clip deployment when OTSC clips are used[41,52]. There are only a few case reports on successful closure of a chronic spontaneous oesophageal rupture and a consequently developed fistula with endoscopic clips[9,11].

Endoscopic vacuum therapy may be helpful in reducing the inflammatory cavity and closing the remaining fistula with good localization in the case of chronic injuries and mediastinal/pleural inflammation[37,45]. Following initial stent placement and removal in the treatment of an early, well-defined injury, a cavity marked by chronic inflammation may remain, one which may not be resolved with primary clipping alone. In these cases, EVT and/or surgical treatment (VATS) represent the primary therapeutic procedure[34-36,45].

Very few articles report long-term follow-up data. The biggest and most detailed report is a North American study which evaluated gastrointestinal defects in 188 patients treated with OTSC. Success was achieved in 60.2% of the patients in a median follow-up of 146 d. The long-term rate for clinically successful closure of perforations (90%) and leaks (73.3%) was significantly higher than that of fistulas (42.9%). The study also showed significantly greater long-term success when OTSCs were used in primary therapy.

On the whole, it is clear that closure with clips shows the best results in the treatment of early injuries, and the success rate for clinical recovery approaches the result for surgical treatment.

A number of case reports and case series reports have been published on the successful outcome of clip closure of endoscopic perforations, but high-evidence, case-controlled, multicentre studies are still missing. This method can only be used under very strict conditions (Figure 1). The introduction of OTSC clips significantly increases the size of treatable lesions (from 1 to 2-3 cm). However, this technique is only used in a limited number of centres. It is important to point out that both conventional TTS and the new OTSC methods are both safe. But a learning curve period and experience will both be necessary in their usage, including the selection of patients suitable for clip treatment. Multidisciplinary teams (surgeon, endoscopy specialist and intensive care therapist) are further important conditions in the successful treatment of oesophageal perforations. Surgical treatment still constitutes the primary therapy in oesophageal perforation. Based on the results so far, we can state that endoscopic closure of early, well-defined oesophageal perforations represents a therapeutic alternative to surgical treatment.