A novel treatment of bromelain and acetylcysteine (BromAc) in patients with peritoneal mucinous tumours: A phase I first in man study.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. CONCLUSION: 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.

Percutaneous lung ablation of pulmonary recurrence may improve survival in selected patients undergoing cytoreductive surgery for colorectal cancer with peritoneal carcinomatosis.

PURPOSE: To analyze the outcomes of patients developing pulmonary metastases (PM) following cytoreductive surgery (CRS) and perioperative intra-peritoneal chemotherapy (IPC) for colorectal cancer (CRC) with peritoneal carcinomatosis. PATIENTS AND METHODS: A retrospective analysis of patients undergoing CRS/IPC for CRC from 1996 to 2016 was performed. Lung-specific disease-free and patient overall survival was analyzed. Patients undergoing percutaneous lung ablative therapy (PLAT) for PM were compared to patients receiving systemic chemotherapy alone. RESULTS: 273 patients underwent CRS/IPC for CRC. Of these, 61 (22%) developed PM. Median time to development of PM was 8 months (range 0-52 months) and 41 patients (67%) had metachronous lesions. Twenty-one PM patients underwent PLAT, either by radio-frequency or micro-wave ablation, for an average of 3 lesions (range 1-12) and 13 (62%) had bilobar disease. The most common post-interventional complication was the development of pneumothorax (71%). Overall survival following development of PM was 18 months and higher in patients undergoing PLAT compared to those treated with systemic chemotherapy (26 vs. 14 months, p = 0.03). In eight cases (38%) local tumor recurrence developed post-PLAT. A peritoneal carcinomatosis index >10 (HR 3.48, 95% CI 1.69-7.19), presence of liver metastases (HR 2.49, 95% CI 1.24-5.03) and PLAT (HR 0.43, 95% CI 0.20-0.93) were identified as significant predictors of overall survival following diagnosis of PM. CONCLUSION: PM develop in approximately a fourth of patients undergoing CRS/IPC for CRC. Of these, about 1/3 may be eligible for PLAT. PLAT is a valuable treatment option providing good local control and potentially prolongation of overall survival.

Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Methodology, Drugs and Bidirectional Chemotherapy.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) combined have been recognized as standard of care for treatment of a subset of patients with peritoneal carcinomatosis (PC). The aim of CRS is to eliminate all macroscopic disease through a series of visceral resections followed by targeting any residual microscopic disease with intraperitoneal chemotherapy, exposing the peritoneal surfaces to a high concentration of chemotherapy with a lower systemic toxicity. Different regimes of intraperitoneal chemotherapy include HIPEC, early postoperative intraperitoneal chemotherapy (EPIC) and bidirectional chemotherapy. The efficacy and modality of treatment with intraperitoneal chemotherapy is dependent on multiple factors including the chosen cytotoxic agent and its pharmacokinetics and pharmacodynamics. There is no standardized methodology for intraperitoneal chemotherapy administration. This review will discuss the pharmacological principles of the various intraperitoneal chemotherapy techniques.

Laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) for refractory malignant ascites in patients unsuitable for cytoreductive surgery.

INTRODUCTION: Malignant ascites (MA) is the abnormal accumulation of fluid in the peritoneal cavity of patients with intraperitoneal dissemination of their disease and is associated with a short life expectancy. The most common clinical feature is a progressive increase of abdominal distention resulting in pain, discomfort, anorexia and dyspnoea. Currently, no treatment is established standard of care due to limited efficacy or considerable toxicity. The objective was to examine the efficacy of laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) in the palliation of refractory MA in patients who were unsuitable for cytoreductive surgery. METHODS: From May 2009 to June 2015, 12 patients with MA due to their peritoneal malignancy were treated with laparoscopic HIPEC. The time between operation and repeat paracentesis, in-hospital data, and the proportion of patients that did not require repeat paracentesis was analyzed. RESULTS: One patient (8%) was admitted to ICU for 1 day. The mean operating time and hospital stay was 149.3 min (range 79-185) and 4.6 days (range 2-11) respectively. Neither high-grade morbidity nor mortality was observed. The median OS was 57 days. In our experience, a complete and definitive disappearance of MA was observed in 83% of patients. Two patients (17%) developed recurrent MA 124 days and 283 days post-HIPEC. CONCLUSION: Laparoscopic HIPEC is a beneficial treatment for the management and palliation of refractory MA and results in an excellent clinical and radiological resolution in patients with a complete resolution observed in selected patients.