OBJECTIVE: Evidences from animal models seem to suggest that minimally invasive surgery may enhance cisplatin diffusion when the drug is administered in the context of post-operative hyperthermic intraperitoneal chemotherapy (HIPEC). The present study evaluates the cisplatin pharmacokinetic profile in a prospective series of women with platinum sensitive recurrent epithelial ovarian cancer treated with open secondary cytoreductive surgery (O-SCS) or minimally-invasive secondary cytoreductive surgery (MI-SCS). METHODS: Cisplatin levels were assessed at 0, 20, 40, 60, and 120 minutes in: 1) blood samples, 2) peritoneal perfusate, and 3) peritoneal biopsies at the end of HIPEC. Median Cmax has been used to identify women with high and low drug levels. Progression-free survival (PFS) was calculated as the time elapsed between SCS+HIPEC and secondary recurrence or last follow-up visit. RESULTS: Nine (45.0%) women received MI-SCS, and 11 (55.0%) O-SCS. At 60 minutes, median cisplatin Cmax in peritoneal tissue was higher in patients treated with MI-SCS compared to O-SCS (Cmax=8.262 µg/mL vs. Cmax=4.057 µg/mL). Furthermore, median cisplatin plasma Cmax was higher in patients treated with MI-SCS compared to O-SCS (Cmax=0.511 vs. Cmax=0.254 µg/mL; p-value=0.012) at 120 minutes. With a median follow-up time of 24 months, women with higher cisplatin peritoneal Cmax showed a longer PFS compared to women with low cisplatin peritoneal levels (2-years PFS=70% vs. 35%; p-value=0.054). CONCLUSIONS: We demonstrate for the first time that minimally invasive route enhances cisplatin peritoneal tissue uptake during HIPEC, further evaluations are needed to confirm the correlation between peritoneal cisplatin levels after HIPEC and survival. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01539785
Biopsy ; Cisplatin ; Cytoreduction Surgical Procedures ; Diffusion ; Disease-Free Survival ; Drug Therapy ; Endoscopy ; Female ; Follow-Up Studies ; Humans ; Injections, Intraperitoneal ; Minimally Invasive Surgical Procedures ; Models, Animal ; Ovarian Neoplasms ; Pharmacokinetics ; Plasma ; Platinum ; Prospective Studies ; Recurrence

Rising rates of obesity has increased the global use of herbal supplements intended to control weight. However, taking these preparations without appropriate medical supervision could increase the risk of manifestation of side effects, especially at the hepatic level. In literature, different cases of acute liver injury consequent to the use of food supplements containing Garcinia cambogia and hydroxycitric acid are reported. This letter aims to review the most recent literature that analysed the herb-induced liver disease due to the use of hydroxycitric acid, from the first alert coming from the European Food and Drug Administration in 2009, to the last recent European food alerts from 2020 to 2021. It is noteworthy that in some cases it demonstrated the relationship between hydroxycitric acid and hepatotoxicity. Therefore, there is a need to draw more attention to the relationship between a safe use and a more awareness in the intake of these supplements, to preserve the safety of the consumers who increasingly purchase food supplements, products that have only nutritive properties and are never curative.
Anti-Obesity Agents/pharmacology* ; Chemical and Drug Induced Liver Injury/etiology* ; Citrates ; Dietary Supplements/adverse effects* ; Humans ; Plant Extracts/pharmacology*