Endoscopic resection of oesophageal gastrointestinal stromal tumours: Promise, pitfalls and the path forward

Abstract

Oesophageal gastrointestinal stromal tumours are rare, anatomically challenging lesions with higher surgical morbidity than their gastric counterparts. Emerging endoscopic resection techniques such as endoscopic submucosal dissection and submucosal tunnelling endoscopic resection show much promise for the management of patients who are not fit for, or wish to avoid the morbidity of, major surgical resection. These techniques require careful patient selection and advanced technical skills. We build on the recent review of such techniques by Vogli et al. Current evidence is limited to small case series with heterogeneity in patient selection, tumor size, and outcomes. Notably, long-term oncological data remain sparse, and complications such as bleeding or perforation may be life-threatening in patients unfit for surgical rescue. Nonetheless, endoscopic approaches have many potential advantages to offer such as preserved quality of life and definitive management of unfit patients.

Key Words: Gastrointestinal stromal tumour; Oesophageal gastrointestinal stromal tumour; Endoscopic resection techniques; Pathology; Surgery; Oesophagectomy; Endoscopy; Diagnosis

Core Tip: Greater awareness and adoption of endoscopic resection techniques will generate more evidence and data for their safety and potential oncologic durability, possibly through multicentre studies. Going forward appropriate patient and tumour selection is key, with careful counselling and consent process for patients.

TO THE EDITOR

We read the paper by Vogli et al[1] on their review showcasing the promising role of endoscopic therapy for oesophageal gastrointestinal stromal tumours (GISTs), published in the World Journal of Gastroenterology, with great interest. GISTs are mesenchymal tumours of the gastrointestinal tract, arising from the interstitial cells of Cajal, also known as the gut’s “pacemaker” cells[2]. Oesophageal GISTs are much rarer than gastric GISTs[2].

The paper describes emerging endoscopic therapies for oncological resection in oesophageal/GISTS - mainly endoscopic submucosal dissection (ESD) and submucosal tunnelling endoscopic resection techniques. Endoscopic subserosal dissection and endoscopic full thickness resection are two less common techniques also described in two of the studies. Table 1 summarises the different endoscopic resection techniques and their respective advantages and limitations. The authors aimed to summarise the current literature on these therapies, which currently just consists of individual published case series, reflecting the relative infancy of these therapies. They examined characteristics in the individual studies such as tumour size, location, resection technique and finally complications that holistically might give insight into the advantages and limitations of these techniques. The increasing popularity of endoscopic resection techniques is reflected in the recent European Society of Gastrointestinal Endoscopy statement attempting to standardize technical steps in resections - such as use of dedicated endoscopic knives, submucosal injection and over the scope closure devices[3,4]. Oesophageal GISTs pose particular challenges to surgeons as resectional surgery can be morbid (for example thoracotomy) and in addition the location to the GOJ often precludes simple laparoscopic stapling[5]. Therefore, advanced endoscopic techniques to treat these lesions in anatomically difficult locations are to be commended.

Table 1 Summary of different endoscopic resection techniques for submucosal lesions such as gastrointestinal stromal tumours.

Endoscopic resection technique	Overview	Advantages	Limitations
ESD	Accurate resection of a lesion under direct endoscopic vision with closure using endoscopic clips	Achieves en bloc resection of large/flat lesions	Risk of full thickness perforation
ESSD	Modification of ESD - dissection down to deeper muscle layers	Removal of lesions in muscularis propria (deeper than traditional ESD)	Higher risk of perforation than traditional ESD
STER	Formation of “submucosal tunnel” proximal to a deeper lesion before resecting/closing the tunnel with clips	Reduced risk of leak/stricture/gas related complications	Size constraints of tunnel - lesions < 4 cm only. Tunnel related complications - bleeding/infection/delayed perforation
EFTR	Full thickness resection of a lesion either tunnelled/non tunnelled	Can tackle deeper/more invasive lesions not amenable to ESD without need for formal resection surgery	Requires closure every time/more advanced equipment and skills. Risk of perforation/Leak from closure. Can be combined with laparoscopy to assist in closure if required and in the stomach or gastro-esophageal junction

ESD: Endoscopic submucosal dissection; ESSD: Endoscopic subserosal dissection; STER: Submucosal tunnelling endoscopic resection; EFTR: Endoscopic full thickness resection.

OESOPHAGEAL VS GASTRIC GISTS

Oesophageal GISTs are distinct from gastric GISTs in many ways. Firstly, as described above, GISTs are much less commonly found in the oesophagus, with recent data from the United States Surveillance, Epidemiology and End Results database reporting 0.5% of GISTS located in the oesophagus compared to 65.2% located in the stomach[4]. Consequently, the molecular biology of gastric GISTS is much better defined, with certain platelet-derived growth receptor alpha mutations associated with better prognosis and greater sensitivity to tyrosine kinase inhibitors such as imatinib[5]. Prognosis and sensitivity to neoadjuvant or adjuvant therapies are unclear in oesophageal GISTs. Diagnosis of oesophageal GISTs assumes a higher level of complexity compared to their gastric counterparts due to anatomic location often within the chest, difficulty in discrimination from benign leiomyomas, and increased perforation risk associated with endoscopic ultrasound and biopsy - which is then subsequently harder to treat[6].

Finally, surgery for oesophageal GISTs is more complex in terms of decision making and skills. Smaller tumours may be treated with enucleation, while larger tumours would be best treated with a formal oesophagectomy; however, the exact size is up for debate. Some papers, suggest that oesophageal GISTs < 5 cm may be treated with enucleation, whereas those > 9 cm should undergo oesophagectomy, but there are no clear international guidelines or consensus on these thresholds[1,6]. Surgery for gastric GISTs is relatively more straightforward provided the gastro-oesophageal junction is not involved or close, with a laparoscopic or open wedge resection of the stomach the most common performed operation for this indication, and the presence of an R1 resection may not necessarily indicate worse survival especially in the presence of sensitivity to imatinib[7]. All these complexities of oesophageal GISTs do validate the need to answer whether complex endoscopic therapy can offer a safe and effective oncological option for these patients, as the Vogli et al’s study[1] aimed to do.

SUMMARY OF STUDY AND OBSERVATIONS

Vogli et al[1] reported five studies reporting their experience with endoscopic resection of oesophageal GISTs. The studies were significantly heterogenous, with variation in tumour size, location and resection technique. Unfortunately, only two studies reported on the histology of resection and whether a “complete, en-bloc” resection was achieved. Complications were reported in all studies - and included perforation, significant bleeding, hydrothorax and post ESD electrocoagulation syndromes. Unfortunately, patient characteristics were not clarified in the study - thus it was not entirely clear whether these patients were unfit for surgery or counselled towards endoscopic treatment for other reasons. Two studies reported follow up of patients for 28 months and 31 months respectively - both reporting no evidence of disease recurrence in their cohorts. The other three studies did not report follow up data. Interestingly, Zhou et al[8] published their case series in the same month as Vogli et al’s paper[1] - with twenty-two oesophageal GISTs managed by ESD (three patients) and submucosal tunnelling endoscopic resection (nineteen patients). Their study cautiously suggested that endoscopic resection might be safe for tumours with “low-risk” endoscopic ultrasound features and less than 5 cm in size.

CONCLUSION

Patients are living longer and older patients are being diagnosed with oesophageal GISTs, despite the overall rarity of the diagnosis. Novel endoscopic therapies that can obviate the need for morbid invasive surgery while achieving the same oncological outcomes may be the key to future treatment. However, patients should be counselled for potentially significant or life threatening complications such as bleeding or perforation, which can be especially fatal if patients are not fit for surgery to rescue such complications. Furthermore, we are severely lacking long term data for oncological outcomes such as 5-year survival or disease-free survival. Patients should be counselled carefully for incomplete resection or tumour recurrence prior to endoscopic resection. However, stronger evidence than small case series are required. Due to the rarity of oesophageal GISTs this might need to be a multi-centre study.

Nevertheless, these newer modern endoscopic techniques may still hold certain benefits - such as preservation of quality of life (especially when compared to a majorly morbid operation such as oesophagectomy). A multidisciplinary approach with endoscopists, surgeons, radiologists and oncologists will take into account clinical, anatomical and technical factors to give the best outcomes and reduce complications of endoscopic treatment for these rare but complex lesions.