Regenerative medicine for complex gastrointestinal transmural defects: a silver bullet or just another tool in the endoscopist’s arsenal?

10.1055/a-2665-1777

Gastrointestinal (GI) wall defects, also known as transmural defects, comprise three distinct entities: perforation, leak, and fistula [1]. While perforation may occur spontaneously (e.g. Boerhaave syndrome), be induced by foreign bodies, or result from endoscopic manipulation, leaks and fistulas are typically related to surgery or radiotherapy. A GI leak, for example, is characterized by the disruption of a surgical anastomosis, allowing contents to escape into the surrounding space. A fistula, in contrast, implies the presence of a tract connecting the GI lumen with the skin or a contiguous organ (e.g. a rectovaginal fistula). In chronic fistulas, the tract is typically lined with epithelium.

“The authors are to be commended for introducing regenerative medicine into the endoscopist’s therapeutic arsenal for GI transmural defects.”

Leaks and fistulas represent the Achilles’ heel of GI surgery, often resulting in prolonged hospital stays, increased healthcare costs, and higher mortality. These conditions are usually associated with inflamed, ischemic, fibrotic, or irradiated tissue – factors that contribute to impaired healing. The cornerstone of treatment includes sepsis control, adequate drainage, nutritional support, and correction of perpetuating factors (e.g. a distal GI stricture). In recent years, endoscopic therapy has emerged as a valuable adjunct, employing a broad array of tools, including but not limited to through-the-scope clips, over-the-scope (OTS) clips, stents, injectable sealants, scaffolds, suturing, and endoscopic vacuum therapy (EVT) [2]. The wide variety of endoscopic treatment options reflects the complexity of fistula management, and the modest clinical success rates range from 40% to 80% [2].

In this issue of Endoscopy, Nachira et al. integrated the concept of regenerative medicine into the endoscopic management of complex GI transmural defects [3]. The authors harvested 30 mL of adipose tissue from the patient’s hip and isolated the stromal vascular fraction (SVF) using a simple process of sequential filtration followed by centrifugation. In the same session, they injected the SVF into the submucosa at four quadrants around the fistulous orifice using a 20- or 22-gauge needle catheter, aiming to seal the defect. According to the authors, the autologous SVF contains “mesenchymal stromal cells and extracellular matrix fragments, which promote healing through anti-inflammatory, proangiogenic, immunomodulatory, and regenerative properties.”

From October 2020 to June 2024, they treated 30 patients – 15 with esophageal and 15 with rectal transmural defects. Defects measuring 5 mm or more were classified as large. In these cases, and when technically feasible, defects were sutured before SVF injection. Previous treatments in the esophageal group included self-expandable metal stent (SEMS) placement (n = 3), EVT (n = 2), and surgery (n = 1). In the rectal group, SEMS (n = 1) and OTS clip (n = 1) placement had been attempted. The combination of suturing and SVF injection was used in 5 patients (33.3%) with esophageal defects and 10 patients (66.7%) with rectal defects. In the esophageal group, complete closure was achieved in 10 patients (66.7%) after the first session. An additional four patients achieved closure after a second session, yielding a clinical success rate of 93.3%. The median interval between sessions was 41 days. In the rectal group, six patients (40.0%) achieved closure after the first session, with a total of up to four sessions required to reach a 60.0% clinical success rate (9/15). The mean time between sessions was 82 days.

Assessing the literature on endoscopic therapy for GI leaks and fistulas remains challenging. Most available studies are case series or systematic reviews thereof, often describing heterogeneous defects in patients with various surgical histories and oncologic treatments. This series by Nachira et al. series is no exception.

In the esophageal group, the heterogeneity was marked – for example, one patient had a traumatic defect identified 12 days before SVF injection, while another had a postoperative chronic fistula detected 1800 days before SVF injection. Notably, 60% of patients in this group had not undergone any prior endoscopic intervention before SVF injection. In our own preliminary experience with EVT for postoperative upper GI wall defects in 30 patients, we observed a clinical success rate of 86.7% [4]. Although EVT requires prolonged hospitalization and the use of a transnasal aspirating tube, it offers reliable infection control and efficacy in large defects – supporting its role as a first-line therapy for postoperative upper GI leaks and acute fistulas.

In the rectal group, most patients presented with postoperative chronic rectovesical fistulas, although there was variability in radiotherapy history and the interval between fistula formation and SVF injection (ranging from 21 to 2145 days). Again, most patients (13/15) had not previously received endoscopic treatment. The fistulous orifices were generally small, with a median diameter of 5 mm (interquartile range 2 mm), suggesting the use of OTS clips as a reasonable alternative. It is important to remember that the use of OTS clips for chronic GI wall fistulas typically yields a clinical success rate of 40%–50% [5]. Despite combining endoscopic suturing (in 10 patients) with up to four SVF injection sessions, the clinical success rate remained modest at 60%, reflecting the complexity of managing postoperative chronic rectovesical and rectovaginal fistulas. Notably, SVF storage could theoretically enable multiple injections from a single adipose tissue harvest [6].

The authors are to be commended for introducing regenerative medicine into the endoscopist’s therapeutic arsenal for GI transmural defects. More importantly, they underscored the need for a resilient and creative multidisciplinary approach in managing these patients. What’s next? We look forward to studies with better patient selection and the integration of tissue-engineered scaffolds with SVF injection.

Publication History

Article published online:
02 September 2025

• References

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