Date Published: July 7, 2017
Publisher: Public Library of Science
Author(s): Gorana Gasljevic, Ibrahim Edhemovic, Maja Cemazar, Erik Brecelj, Eldar M. Gadzijev, Maja M. Music, Gregor Sersa, Obul Reddy Bandapalli.
Electrochemotherapy of colorectal liver metastases has been proven to be feasible, safe and effective in a phase I/II study. In that study, a specific group of patients underwent two-stage operation, and the detailed histopathological evaluation of the resected tumors is presented here. Regressive changes in electrochemotherapy-treated liver metastases were evaluated after the second operation (in 8–10 weeks) in 7 patients and 13 metastases when the treated metastases were resected. Macroscopic and microscopic changes were analyzed. Electrochemotherapy induced coagulation necrosis in the treated area encompassing both tumor and a narrow band of normal tissue. The area became necrotic, encapsulated in a fibrous envelope while preserving the functionality of most of the vessels larger than 5 mm in diameter and a large proportion of biliary structures, but the smaller blood vessels displayed various levels of damage. At the time of observation, 8–10 weeks after electrochemotherapy, regenerative changes were already seen in the peripheral parts of the treated area. This study demonstrates regressive changes in the whole electrochemotherapy-treated area of the liver. Further evidence of disruption of vessels less than 5 mm in diameter and preservation of the larger vessels by electrochemotherapy is provided. These findings are important because electrochemotherapy has been indicated for the therapy of metastases near major blood vessels in the liver to provide a safe approach with good antitumor efficacy.
The most common hepatic neoplasms are metastatic carcinomas predominantly originating from colorectal neoplasms . The majority of patients with colorectal liver metastases have unresectable tumors at the time of diagnosis . Only 10–20% of patients are eligible for surgical resection, which depends on the tumor size as well as the number and position of the metastatic lesions . In patients who are not eligible for major hepatectomy, resection, systemic chemotherapy or a combination of both is performed. The other treatment options for liver metastases are local ablation therapies, such as intratumoral injection of ethanol, radiofrequency ablation or cryotherapy .
This study is the first to demonstrate regressive changes induced in colorectal liver metastases by electrochemotherapy in the liver. Electrochemotherapy induces coagulation necrosis of the treated area containing both tumor and normal tissues. The area became necrotic, encapsulated in a fibrous envelope, and the functionality of most of the vessels larger than 5 mm in diameter and a large proportion of biliary structures was preserved. In contrast, the smaller blood vessels displayed various levels of damage depending on the distance from the electrodes, i.e., the strength of the electric field. Regenerative changes were already observed in the peripheral parts of the treated area at the time of the observation, i.e., at 8–10 weeks after the electrochemotherapy.