Department of Surgery, St George Hospital, Kogarah, NSW, Australia.
Department of Radiology, St George Hospital, Kogarah, NSW, Australia.
Eur J Surg Oncol. 2021 Jan;47(1):115-122. doi: 10.1016/j.ejso.2019.10.033. Epub 2019 Oct 31.
Bromelain (Brom) and Acetylcysteine (Ac) have synergistic activity resulting in dissolution of tumour-produced mucin both in vitro and in vivo. The aim of this study was to determine whether treatment of mucinous peritoneal tumour with BromAc can be performed with an acceptable safety profile and to conduct a preliminary assessment of efficacy in a clinical setting.
Under radiological guidance, a drain was inserted into the tumour mass or intraperitoneally. Each patient could have more than one tumour site treated. Brom 20-60 mg and Ac 1·5-2 g was administered in 5% glucose. At 24 h, the patient was assessed for symptoms including treatment-related adverse events (AEs) and the drain was aspirated. The volume of tumour removed was measured. A repeat dose via the drain was given in most patients. All patients that received at least one dose of BromAc were included in the safety and response analysis.
Between March 2018 and July 2019, 20 patients with mucinous tumours were treated with BromAc. Seventeen (85%) of patients had at least one treatment-emergent AE. The most frequent treatment-related AEs were CRP rise (n = 16, 80%), WCC rise (n = 11, 55%), fever (n = 7, 35%, grade I) and pain (n = 6, 30%, grade II/III). Serious treatment-related AEs accounted for 12·5% of all AEs. There were no anaphylactic reactions. There were no deaths due to treatment-related AEs. An objective response to treatment was seen in 73·2% of treated sites.
Based on these preliminary results and our preclinical data, injection of BromAc into mucinous tumours had a manageable safety profile. Considerable mucolytic activity was seen by volume of mucin extracted and radiological appearance. These results support further investigation of BromAC for patients with inoperable mucinous tumours and may provide a new and minimally invasive treatment for these patients.
菠萝蛋白酶（Brom）和乙酰半胱氨酸（Ac）具有协同作用，可在体外和体内溶解肿瘤产生的粘蛋白。本研究旨在确定用 BromAc 治疗粘液性腹膜肿瘤是否具有可接受的安全性，并在临床环境中对其疗效进行初步评估。
在放射学引导下，将引流管插入肿瘤肿块或腹腔内。每个患者可治疗多个肿瘤部位。在 5%葡萄糖中给予 Brom 20-60mg 和 Ac 1.5-2g。在 24 小时时，评估患者的症状，包括与治疗相关的不良事件（AE）和引流管抽吸情况。测量肿瘤清除的体积。大多数患者重复通过引流管给药。所有接受至少一剂 BromAc 的患者均纳入安全性和反应分析。
2018 年 3 月至 2019 年 7 月，对 20 例粘液性肿瘤患者进行了 BromAc 治疗。17 例（85%）患者至少有一次治疗后出现 AE。最常见的与治疗相关的 AE 是 CRP 升高（n=16，80%）、WCC 升高（n=11，55%）、发热（n=7，35%，I 级）和疼痛（n=6，30%，II/III 级）。严重与治疗相关的 AE 占所有 AE 的 12.5%。没有过敏反应。没有因治疗相关 AE 导致的死亡。在治疗的 73.2%的部位观察到客观的治疗反应。
基于这些初步结果和我们的临床前数据，将 BromAc 注入粘液性肿瘤具有可管理的安全性。通过提取的粘蛋白体积和影像学表现观察到明显的粘蛋白溶解活性。这些结果支持对不能手术的粘液性肿瘤患者进一步研究 BromAC，并可能为这些患者提供一种新的微创治疗方法。
