Background

Perianal fistulizing Crohn’s disease (FCD) comes with significant morbidity and severe reduced quality of life. Treatment of FCD is challenging and includes immunosuppressive drugs, antibiotics and surgery. All therapies are associated with high recurrence rates. Platelet-rich stroma (PRS) is a combination of platelet-rich plasma (PRP) and stromal vascular fraction (SVF). Autologous PRS includes stromal cells in their matrix with stimulating factors, plays an essential role in wound repair and defence mechanisms against infection and is easy to obtain and inject. Because of its operating mechanism, PRS could be of additional value in patients with refractory FCD. This study aims to assess the feasibility, safety and efficacy of local injection of PRS in patients with refractory FCD.

Methods

After informed consent, 10 patients (age ≥16 years) with refractory FCD were included between March 2018 and July 2019. Exclusion criteria were rectovaginal fistulas, persistent proctitis and pelvic abscesses. All patients underwent surgery with harvesting of subcutaneous fat and venous blood sampling to obtain 6 ml of PRS (1 ml of SVF resp. 5 ml of PRP), excision of the external opening(s), fistula curettage, and injection of PRS in the fistula wall and closure of the internal opening. A pre- and postoperative MRI was performed. Endpoints were clinical outcome, both closure and absence of discharge at physical examination, patient-reported outcome (no effect/moderate effect/major effect), as well as radiological outcome (van Assche score). From 3 months postoperative, re-injection of PRS was considered in patients with unfavourable clinical and/or radiological outcome.

Results

All patients (4:6 female:male; median age 33 (IQR 22.9–38.7) had infralevatoric fistulas with a median van Assche score of 17 [range 14–20] without rectal involvement and abscesses. Median follow-up was 6 months [4–12]. The median duration of FCD was 4 years (IQR 2–5). The median number of drugs given were 4 [1–7] and number of operations 3 [2–3], including stoma formation in 2 patients. Crohn’s disease activity outside the anorectum was present in all patients. 7 patients underwent 1 PRS injection and 3 patients 2 injections. There were no complications of the PRS injection. Fistula closure was present in 5 patients and open in 5 patients, of which 2 patients had no signs of discharge. One patient underwent restoration of bowel continuity. Of 7 postoperative MRIs available to date, median decrease of van Assche score was 4 (17 vs. 13)[0–15]. Patient-reported outcome was major effect in 4, moderate effect in 3, and no effect in 3 patients.

Conclusion

Autologous PRS appears to be feasible, safe and promising in the treatment of refractory perianal fistulizing Crohn’s disease.

中文翻译：

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P359富血小板基质注射（PRS）作为克罗恩病难治性肛周瘘管的新型外科治疗：一项先导研究

背景

肛周瘘管克罗恩病（FCD）的发病率很高，生活质量也大大降低。FCD的治疗具有挑战性，包括免疫抑制药，抗生素和手术。所有疗法均与高复发率相关。富血小板基质（PRS）是富血小板血浆（PRP）和基质血管部分（SVF）的组合。自体PRS在基质中包含具有刺激因子的基质细胞，在伤口修复和防御感染的机制中起着至关重要的作用，并且易于获取和注射。由于其运行机制，PRS在难治性FCD患者中可能具有附加价值。这项研究旨在评估难治性FCD患者局部注射PRS的可行性，安全性和有效性。

方法

知情同意后，于2018年3月至2019年7月纳入10例难治性FCD患者（年龄≥16岁）。排除标准为直肠阴道瘘，持续性直肠炎和盆腔脓肿。所有患者均接受了皮下脂肪的采集和静脉血取样的手术，以获得6 ml的PRS（1 ml的SVF或5 ml的PRP），切开外部开口，刮除刮宫术，并将PRS注入瘘管壁和内部开口封闭。术前和术后进行了MRI检查。终点为临床结局，体格检查中是否关闭和未出院，患者报告的结局（无影响/中度影响/重大影响）以及放射学结局（van Assche评分）。从术后3个月起，

结果

所有患者（4：6，女性：男性；中位年龄33（IQR 22.9–38.7））均患有肛管下瘘，van Assche评分中位数为17 [范围14–20]，无直肠受累和脓肿，中位随访6个月[ [4–12]。FCD的中位持续时间为4年（IQR 2–5）。给予的药物中位数为4 [1–7]，手术次数3 [2–3]，包括2位患者的造口。所有患者均存在肛门直肠克罗恩病活动，其中7例接受1例PRS注射，3例进行2例注射，无PRS注射并发症，5例存在瘘管闭合，5例开放，其中2例开放患者无出院征象，一名患者进行了肠连续性恢复，迄今为止，在7例术后MRI中，van Assche评分的中位数下降了4（17 vs. 13）[0-15]。患者报告的结局为4例为主要疗效，3例为中效，3例无效果。

结论

自体PRS在难治性肛周瘘管克罗恩病的治疗中似乎是可行，安全且有希望的。