Irreversible electroporation to bring initially unresectable locally advanced pancreatic adenocarcinoma to surgery: the IRECAP phase II study.

OBJECTIVES: The aim of the IRECAP study was to evaluate the rate of locally advanced pancreas cancer patients (LAPC) who could undergo R0 or R1 surgery after irreversible electroporation (IRE). MATERIALS AND METHODS: IRECAP study is a phase II, single-center, open-label, prospective, non-randomized trial registered at clinicaltrials.gov (NCT03105921). Patients with LAPC were first treated by 3-month neo-adjuvant chemotherapy in order to avoid inclusion of either patients with LAPC having become resectable after chemotherapy or patients with rapid disease progression. In cases of stable disease, IRE was performed percutaneously under CT guidance. Surgery was planned between 28 and 90 days after IRE. Tumor specimens were studied to evaluate the resection margins (R0/R1/R2). RESULTS: Six men and 11 women were included (median age 61 years, range 37-77 years). No IRE-related death was observed. Ten patients (58%, 10/17) experienced 25 serious adverse events related to IRE. Four patients progressed between IRE and surgery and were excluded from surgery. Thirteen patients were finally operated, six withheld for pancreas resection, three for diffuse peritoneal carcinosis, two for massive vascular entrapment, and one for hepato-cellular carcinoma not diagnosed before surgery. Rate of R1-R0 was 35% (n = 6/17). Median overall survival was 31 months (95% CI; 4-undefined) for the six patients with R0/R1 resection and 21 months (95% CI; 4-25) for the 11 patients without resection or R2 resection (logrank p = 0.044). CONCLUSION: After neoadjuvant chemotherapy, IRE could provide R0 or R1 resection in 35% of LAPC, which seems to be associated with higher OS. CLINICAL RELEVANCE STATEMENT: After induction chemotherapy, stable locally advanced pancreatic cancers can be treated by irreversible electroporation, which could lead to a secondary 35% rate of R0 or R1 surgical resection which may be associated with a significantly higher overall survival. KEY POINTS: • In cases of unresectable LAPC (locally advanced pancreatic cancer), percutaneous irreversible electroporation (pIRE) is feasible (100% success rate of the procedure), but is associated with a 58% rate of grade 3-4 adverse events. • In patients with unresectable LAPC, pIRE could lead 35% of patients to R0-R1 surgical resection. • From IRE, median overall survival was 31 months (95% CI; 4-undefined) for the patients with R0/R1 resection and 21 months (95% CI; 4-25) for the patients without resection or R2 resection (logrank p = 0.044).

Irreversible Electroporation for Locally Advanced Pancreatic Cancer: Where Do We Stand in 2017?

Pancreatic adenocarcinoma has a very poor prognosis. Complete surgical resection remains the only current curative treatment. Locally advanced pancreatic cancers are considered as unresectable because of involvement of celiac and/or mesenteric vessels. Irreversible electroporation has recently been introduced to induce permanent cell death by apoptosis. Irreversible electroporation is a nonthermal cell-destruction technique that was claimed to allow destruction of cancerous cells with less damage to surrounding supporting connective tissues with collagenic structure (such as nearby blood vessels, biliary ducts, and nerves) than other types of treatment. Applications on pancreatic adenocarcinoma seem promising, and this article is an up-to-date review of the first results.

Application of basic pharmacokinetic concepts to analysis of microdialysis data: illustration with imipenem muscle distribution.

BACKGROUND: Microdialysis studies of antibacterial tissue distribution in critically ill patients have sometimes led to results that were spectacular but inconsistent with basic pharmacokinetic concepts. OBJECTIVE: To conduct a study of imipenem distribution in the muscle of healthy volunteers and critical care patients in order to compare real-life data with theory. METHODS: Microdialysis catheters were placed into the quadriceps, and probe recoveries were determined individually in vivo using a retrodialysis-by-drug method. Unbound imipenem concentrations were determined by high-performance liquid chromatography in plasma ultrafiltrates and muscle dialysates, and submitted to noncompartmental pharmacokinetic analysis. RESULTS: Individual unbound imipenem concentrations in plasma and muscle extracellular fluid were virtually superimposed at any time, both in healthy volunteers and in critical care patients. CONCLUSION: These new results are not consistent with previously published data obtained in similar conditions by another group, but they are in agreement with results previously obtained in rats, as well as being consistent with basic pharmacokinetic concepts.