Ovine forestomach matrix as a novel adjunct to promote healing of low output enterocutaneous fistulae in high-risk surgical patients

Abstract

Background

The development of enterocutaneous fistulas (ECF) after emergency laparotomies is not uncommon. Management is difficult and options limited. Studies suggest ovine forestomach matrix (OFM) grafts may be viable treatment options for complex wounds. The goal of this study was to investigate the use of OFM in the treatment of ECFs.

Methods

Patients with ECFs as a result of emergency laparotomy were treated with OFM. Wounds were appropriately debrided and OFM was applied. A secondary dressing was applied and left on for a minimum of 7 days. Patients were followed at regular intervals to monitor progression of wound healing.

Results

Three patients were included in the case series. One patient developed ECF after bowel resection secondary to gunshot wounds. OFM was applied and upon follow up, the wound was significantly healed. The second patient developed ECF after bowel resection secondary to being struck by a vehicle. OFM was applied and at two week follow up the fistula was closed. The third patient developed ECF after major small bowel resection secondary to acute mesenteric ischemia. OFM was applied and the ECF was fully closed at one month.

Conclusion

This case series highlights the utilization of OFM to augment wound healing in patients with ECFs. This pilot study demonstrates the excellent results achieved with OFM as an adjunct for difficult wounds such as ECFs with the ability to accelerate healing.

Highlights

• •OFM was applied to complex wounds with low-output enterocutaneous fistulas.
• •All patients achieved over 90% wound closure after OFM treatment.
• •OFM use led to fistula closure without adverse events in high-risk patients.
• •The preserved matrix supported healing and tissue regrowth.
• •OFM shows promise as a wound healing adjunct after emergency surgery.

Introduction

Following major abdominal surgery, enterocutaneous fistulae (ECF) are a dreaded and challenging complication with a high associated mortality rate. Definitive treatment options for ECFs are lacking. One potential solution is the use of an extracellular matrix (ECM) based soft tissue graft. ECMs have been previously utilized to promote wound healing for a multitude of wound types, ranging from burn injuries to pressure ulcers. Ovine forestomach matrix (OFM) is an ECM bioscaffold isolated from sheep forestomach tissue that has been shown to be effective in tissue healing [1], [2]. OFM creates a microenvironment that promotes wound healing by providing growth factors that can facilitate wound healing. This brief report aimed to highlight the novel use of OFM grafts to improve healing for wounds associated with low output ECFs following major abdominal surgery. At our institution, high output ECFs were initially managed by bowel rest, total parental nutrition (TPN), and local wound care. Fistula output was monitored daily and less than 200 mL/day of recorded drainage was considered to be a low output fistula. This research was part of a prospective multi-center registry utilizing central Institutional Review Board (IRB) approval with external reliance approval from the Louisiana State University Health Sciences Center IRB (#2297).

Case report #1

A 60-year-old man with history of Hepatitis C, polysubstance abuse, nicotine use, and severe malnutrition (BMI = 17 kg/m²) presented with multiple gunshot wounds to his abdomen. The patient underwent emergent exploratory laparotomy with multiple small and large bowel resections with bowel anastomoses performed. Post-operative course was complicated by multiple anastomotic leaks and an inability to secondarily close the abdominal fascia. The patient subsequently developed a large abdominal wall wound with an ECF that was still present approximately three months after his initial presentation and measured 15.5 × 5.5 cm (Fig. 1A). The patient underwent placement of an OFM graft (3-layer, Myriad Matrix™ Soft Tissue Bioscaffold, Aroa Biosurgery Limited) and a morselized form (Myriad Morcells™, Aroa Biosurgery Limited) in accordance with the manufacturer's recommendations. The OFM grafts were placed on the wound at bedside with a non-adherent primary dressing and standard negative pressure wound therapy (NPWT) as a secondary dressing (Fig. 1B). The patient underwent routine NPWT changes without issue. Two months later, the wound had significantly improved, with the defect measuring 6 × 5 cm (Fig. 1C). After 8 months, the wound was 4 × 3 cm (Fig. 1D), and at 1 year, was 3 × 2 cm (Fig. 1E). Overall, this high-risk patient avoided any further surgery and did not develop any adverse complications such as infection or wound dehiscence. OFM graft placement resulted in approximately 93.8% wound closure and possibly contributed to accelerated closure of the fistula.

Fig. 1.

Case 1. (A) Initial wound before application of OFM graft which measured 15.5 × 5.5 cm. (B) Immediately after placement of OFM. (C) 2 months after OFM placement, 6 × 5 cm. (D) 8 months after OFM placement, 4 × 3 cm. (E) 1 year after OFM placement, 3 × 2 cm.

Case report #2

A 41-year-old woman with history of bipolar disorder, schizophrenia, severe malnutrition (BMI = 19 kg/m²), and nicotine use underwent an emergent exploratory laparotomy after being struck by a motor vehicle as a pedestrian. Small bowel resections with anastomosis of the bowel and abdominal closure were performed. In the post-operative period, the patient developed fascial dehiscence with a high-output ECF (Fig. 2A). Approximately six weeks following the initial abdominal surgery, the patient underwent the placement of morselized OFM with a non-adherent primary dressing and DERMABOND* topical skin adhesive as the secondary dressing (Fig. 2B). The patient's wound measured 9 × 1.5 cm at the time of placement. Dressings were maintained until follow-up 14 days later. At that time, the wound measured 3 × 1.5 cm (Fig. 2C). At three-month follow-up, there was complete closure of the wound and the ECF (Fig. 2D).

Fig. 2.

Case 2. (A) Initial wound dehiscence. (B) Wound before placement of morselized OFM, 9 × 1.5 cm. (C) 14 days after OFM placement, 3 × 1.5 cm. (D) 3 months after OFM placement, full wound closure.

Case report #3

A 46-year-old woman with history of obesity (BMI = 35 kg/m²) presented with acute mesenteric ischemia. An emergency laparotomy was performed with resection of the majority of the small bowel and a superior mesenteric artery thrombectomy. The patient underwent anastomosis of the remaining small intestine and abdominal closure. The patient then developed an anastomotic leak with superficial wound dehiscence and ECF (Fig. 3A). The open wound measured 19 × 6.8 cm. Morselized OFM (500 mg) was placed, with a non-adherent primary dressing and a standard NPWT secondary dressing. At one-month follow-up, the fistula was fully closed with 67% wound closure measuring 11 × 4 cm (Fig. 3B). Approximately four months after OFM placement, the wound was 1.5 × 0.5 cm, resulting in over 95% wound closure (Fig. 3C).

Fig. 3.

Case 3. (A) Initial wound before OFM placement, 19 × 6.8 cm. (B) 1 month after OFM placement, 11 × 4 cm. (C) Four months after OFM placement 1.5 × 0.5 cm.

Discussion

Development of ECFs following emergency abdominal surgery is a feared complication, as there is no definitive and expedient treatment option available [3], [4]. In this study, all three patients experienced greater than 90% wound closure and subsequent ECF closure without adverse complications. Spontaneous ECF closure rates are low as they are also commonly associated with large and complex abdominal wall wounds. This pilot study demonstrated rapid closure of the ECF as well as the abdominal wounds, resulting in a better quality of life for these patients. In particular, our patient population was at high risk for failure of proper wound healing due to their co-morbidities including use of nicotine and poor baseline nutritional status [5], [6]. After initial management of the high output fistula, OFM provided an adjunct to improve the wound microenvironment to facilitate wound healing.

Unlike other commonly employed xenografts or biomaterials, the OFM material is a porous scaffold that is rapidly repopulated with cells and vasculature [7]. It contains many biomolecules that assist in inhibiting degradative enzymes and promote vascular ingrowth, which would not be present in synthetic materials commonly used in fistula repair [8]. Additionally, the native extracellular architecture is largely preserved in OFM, something that may be damaged by the processing methods for other biologically-derived sources [7]. This structure gives the OFM material greater persistence within the fistula tract to promote healing. OFM has also been shown to encourage significantly increased vascularization compared to other biologic materials like small intestine submucosa [9], [10]. Collectively, these properties of OFM allow it to create an improved local microenvironment within the fistula tract to calm inflammation and support tissue ingrowth and closure of the fistula. It likely also aids the healing of the surrounding wound as well.

Based upon the results of this pilot study, we demonstrated that OFM can be an adjunct to improve the closure of low output ECFs. Following a standardized approach to manage high output drainage, the use of OFM helped to close the ECF in three patients with a high risk of wound complications. At our institution, we will continue to increase our experience with this technique and refine our existing guidelines for management of low output ECFs. As this research was part of a multi-center registry, knowledge sharing will allow other institutions to develop similar processes for management of low output fistulas in high-risk post-operative surgical patients. A prospective multi-center study will allow for improvement of guidelines to manage complex post-operative wounds in patients with ECFs.

Conclusions

In conclusion, ECFs following emergency abdominal surgery are a complex post-operative surgical complication. While definitive treatment options are limited, this case series demonstrated that OFM is a cost effective and readily available novel therapy that can be used to accelerate ECF closure without adverse events. Future investigational efforts will focus on increasing sample size and also performing a comparative analysis with a control arm.

CRediT authorship contribution statement

Sophia Trinh: Writing – original draft, Investigation, Writing – review & editing. Joseph Mason: Writing – review & editing. Paige Deville: Writing – review & editing, Investigation. Dhanushka Vitharana: Writing – review & editing, Data curation. John Hunt: Writing – review & editing, Investigation. Alan Marr: Writing – review & editing, Investigation. Lance Stuke: Writing – review & editing, Investigation. Patrick Greiffenstein: Writing – review & editing, Investigation. Alison Smith: Investigation, Writing – review & editing, Supervision.

Statement of informed consent

Written informed consent was obtained from the patient for enrollment in the prospective study.

Statement of human and animal rights

All procedures followed were in accordance with the ethical standards of the committee responsible on human experimentation (institutional and national) and with the Helsinki Declaration.

Statement of funding

Research funding was provided by Aroa Biosurgery Limited as part of a research grant.

Declaration of competing interest

Alison Smith is a paid consultant for Aroa Biosurgery Limited (Auckland, New Zealand) and on the advisory board for Prytime Medical. The other authors declare no conflicts of interest.