Tissue glue: a potential role in the management of intraoperative oesophageal perforation

Abstract

An 85-year-old man suffering from oropharyngeal dysphagia due to a pharyngeal pouch and cricopharyngeal spasm underwent endoscopic stapling of the pouch under general anaesthesia. During the procedure, an iatrogenic perforation of the oesophagus was noticed. After considering several options, 5 mL of Tisseel tissue glue was used to seal the perforation intraoperatively. The patient was started on intravenous co-amoxiclav, kept nil by mouth and fed via a nasogastric tube. After 4 days of observation mediastinal collection and any leakage was ruled out with a gastrografin contrast swallow procedure. At this point he was considered safe for oral intake.

Background

As many as 70% of oesophageal perforations have been reported to be due to iatrogenic causes.^{1 2} The oesophageal wall, being weakest at the pharyngo-oesophageal junction, may also contribute an additional risk of perforation during pharyngeal pouch operations and other endoscopic procedures at this site.² This potentially life-threatening complication does not have any universally accepted intraoperative gold standard treatment option. Currently, some authors have argued the benefit of non-operative treatments in a carefully selected small cohort of patients; however, the majority of patients will undergo operative management.³

Possible surgical options include oesophageal repair and closure using tissue flaps, and oesophageal resection especially in patients with a diseased oesophagus.^{4 5} Some of the non-operative management options include nasogastric feeding with supportive treatment, removable oesophageal stents and closure with metallic clips. Despite the variety of management options, treatment failure remains significant for both operative and non-operative cases. For example, with surgical repair, 30% of patients have been reported to have ongoing leakage. One of the biggest determinants of reducing the mortality of patients with oesophageal perforation is early detection and treatment.^{2 6} Although iatrogenic perforations noted immediately during endoscopic instrumentation has been associated with better outcomes, a treatment technique that could be just as quick may be able to reinforce that advantage.

Case presentation

An 85-year-old man with diabetes presenting with dysphagia and regurgitation was subsequently diagnosed with a small pharyngeal pouch along with associated significant cricopharyngeal muscle spasm. The patient was initially treated conservatively for a few years and had an unsuccessful pharyngeal pouch stapling procedure elsewhere 18 months prior. He was fully assessed at Ninewells Hospital (Dundee). Treatment options, that is, cricopharyngeal balloon dilatation±botox injection, endoscopic pharyngeal pouch stapling or laser division of the bar, were discussed.

Investigations

Preoperative investigations

The patient underwent barium swallow/video fluoroscopy which showed severe spasm of the cricopharyngeus muscle. The patient also had prior CT scan to assess the thickness of the oesophageal wall. This showed that the wall was not thinned out due to previous stapling.

Differential diagnosis

Possible differential diagnoses for this patient may fall under two subcategories of dysphagia causes: neuromuscular and obstructive pathology. A potential neuromuscular cause would be cricopharyngeal achalasia, while relevant obstructive causes include cervical oesophageal stricture and upper oesophageal cancer as these may manifest with similar dysphagic symptoms that the patient initially presented with.⁷

Treatment

The patient was not very keen to receive botox injections as it only offered temporary remedy, thus opting for surgical division of the cricopharyngeal bar. Intraoperatively a small pouch with hypertrophy of the pharyngeus muscle was identified (as shown in figure 1). The bar was divided using an Ethicon Endostapler, the primary aim of the operation being to divide the entire length of the circular fibres of the cricopharyngeus. This was successfully achieved (as shown in figure 2) but resulted in a 1.5 cm × 2.5 cm diamond-shaped perforation at the pharyngo-oesophageal junction (as shown in figure 3).

Figure 1.

Oesophageal bar. The endoscopic view shows an oesophageal bar with prominent cricopharyngeus prestapling.

Figure 2.

Obliteration of the oesophageal bar. The figure shows successful obliteration of the oesophageal bar poststapling.

Figure 3.

Pharyngo-oesophageal junction defect. The figure shows an endoscopic view of a diamond-shaped defect noticed at the pharyngo-oesophageal junction poststapling.

Three possible treatment options were considered for resolution:

• Surgical repair.

• Supportive treatment keeping the patient nil by mouth (NBM) and enabling spontaneous healing.

• Tissue glue (eg, Tisseel) to seal the perforation.

Treatment by external surgical approach could have been an option, but this would have resulted in surgical excision and closure of the leak area with additional risk. This option would have needed the patient to be kept NBM for at least 7–10 days.

It was agreed by two operating surgeons that tissue glue was the best option and 2 mL of Tisseel tissue glue was applied to the area of defect using a long laparoscopic applicator needle (see figure 4). The patient was started on intravenous co-amoxiclav, kept NBM and fed through a nasogastric tube.

Figure 4.

Defect after the application of Tisseel. The figure shows an endoscopic view of the previous pharyngo-oesophageal defect (as seen in figure 3) after Tisseel sealant was applied.

Outcome and follow-up

On day 2 postprocedure the patient underwent a planned CT scan of the neck. On day 4 the patient had a gastrografin contrast swallow procedure. These investigations confirmed the absence of mediastinal collection and/or leakage of contrast. At this point, it was deemed safe for the patient to commence oral intake and he was subsequently discharged.

Discussion

According to the manufacturer’s instructions, Tisseel is intended to be used for two main purposes. It can serve as an adjunct to haemostasis when conventional surgical techniques such as suturing or cautery are ineffective or impractical. Another specific indication for Tisseel is as an adjunct to techniques used to prevent or seal a leakage in colonic anastomosis. However, it has been shown to be useful in a variety of medical specialties ranging from neurosurgery to general surgery.^8–10 For example, Tisseel has been noted to be useful to prevent cerebrospinal fluid leaks after craniotomies and to minimise leaks after gastrojejunal anastomosis in Roux-en-Y gastric bypass surgeries.^{10 11}

With regard to oesophageal perforations, at least two case reports have noted successful outcomes following the use of tissue glue sealants.^{12 13} As described earlier, one of the biggest determinants in reducing mortality associated with oesophageal perforation is the combination of early detection and effective treatment.^{2 6} Tissue glue can be administered quickly and has been shown to be an effective sealant in multiple cases. Based on these properties and favourable patient outcome as mentioned before, we propose that tissue glue (eg, Tisseel) should be considered as a possible alternative intervention for repair of oesophageal perforations. The algorithm of steps taken for this specific patient is shown in figure 5.

Figure 5.

Management protocol.

It is also noteworthy that the patient was a type II diabetic. Despite the condition being associated with poor healing, the outcome of this patient may add weight to the tissue glue’s effectiveness in similar situations.¹⁴

An observation to be considered here is that it is possible the perforation could have been closed by spontaneous healing completely unaided by the tissue glue. The size of perforation has also been noted to affect the success rate of healing (the dimension of this patient’s perforation was 1.5 cm by 2.5 cm).¹² Hence, more evidence is needed to investigate the efficacy of tissue glue with perforations of other sizes. Tissue glue’s effectiveness may also be questionable if a perforation is accompanied by underlying pathology, such as oesophageal infection or malignancy.^{13 15} Therefore, it would be advisable that clinicians take these considerations into account when selecting an appropriate management plan for oesophageal perforation.

The use of polyglycolic acid (PGA) sheets to augment the function of tissue glue has been reported in the literature with successful outcomes. Some advantages of this approach would be its potential to reduce bleeding, the possibility of covering a larger defect and the sheet possibly allowing the tissue glue to remain in situ for a longer period.¹⁶ Potential risks may include higher likelihood of hypersensitivity reactions and infection due to an added foreign body.¹⁶ The application of PGA sheets would also need endoclips to keep them in place. Due to this patient’s perforation located at the pharyngeal space and the potential of swallowing movements dislodging the clips postoperatively, PGA sheets were not considered in this specific scenario.

Contraindications and precautions for the use of tissue glue must also be considered. Tisseel tissue glue is contraindicated in treating massive and brisk arterial or venous bleeding, as a replacement for skin sutures intended to close surgical wounds, intravascular applications (to avoid thromboembolic complications), or application in cases of hypersensitivity to an active substance, any of the excipients or bovine proteins.¹⁷ Tisseel should also be applied as a thin layer, as a thick clot may hamper its effectiveness as a sealant.¹⁷

The use of endoclips (through-the-scope or over-the-scope clips) could be considered a potential alternative option for iatrogenic oesophageal perforation repair as evidence shows successful outcomes through its use.¹⁸ Especially with the introduction of over-the-scope clips, the range of perforation size that can be treated using endoclips has increased (from 1 cm to around 2–3 cm).¹⁹ However, availability and experience in these techniques would be important considerations prior to their use in iatrogenic oesophageal perforations.¹⁹ With this patient, due to the large size of over-the-scope clips and the difficulty in use at the pharyngeal oesophagus, it was not chosen.

An over-the-scope suturing device is another alternative option to deal with oesophageal perforations.²⁰ It is likely superior to endoclips because it enables full-thickness suturing and airtight closure.²⁰ It was not used for this patient as after factoring both cost and efficacy (over-the-scope suturing is expensive), the approach of using tissue glue was deemed adequate. However, if available and warranted, an over-the-scope suturing device may possibly be the best endoscopic perforation repair option in terms of efficacy.²⁰

Learning points.

• Tissue glue could be considered an alternative method for sealing oesophageal perforation, especially in patients who require or would benefit from conservative management.

• In the case of its use, we would suggest considering the algorithm stated in the Discussion section.

• Further long-term outcome data will be needed for validation.