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Purpose: To retrospectively analyse the safety and efficacy of radiofrequency ablation (RFA) versus microwave ablation (MWA) in the treatment of unresectable colorectal liver metastases (CRLM) in proximity to large vessels and/or major bile ducts., Method and Materials: A database search was performed to include patients with unresectable histologically proven and/or (18)F-FDG-PET avid CRLM who were treated with RFA or MWA between January 2001 and September 2014 in a single centre. All lesions that were considered to have a peribiliary and/or perivascular location were included. Univariate logistic regression analysis was performed to assess the distribution of patient, tumour and procedure characteristics. Multivariate logistic regression was used to correct for potential confounders., Results: Two hundred and forty-three patients with 774 unresectable CRLM were ablated. One hundred and twenty-two patients (78 males; 44 females) had at least one perivascular or peribiliary lesion (n = 199). Primary efficacy rate of RFA was superior to MWA after 3 and 12 months of follow-up (P = 0.010 and P = 0.022); however, after multivariate analysis this difference was non-significant at 12 months (P = 0.078) and vanished after repeat ablations (P = 0.39). More CTCAE grade III complications occurred after MWA versus RFA (18.8 vs. 7.9 %; P = 0.094); biliary complications were especially common after peribiliary MWA (P = 0.002)., Conclusion: For perivascular CRLM, RFA and MWA are both safe treatment options that appear equally effective. For peribiliary CRLM, MWA has a higher complication rate than RFA, with similar efficacy. Based on these results, it is advised to use RFA for lesions in the proximity of major bile ducts., Competing Interests: Compliance with Ethical Standards Conflicts of interest On behalf of all authors, the corresponding author states that there is no conflict of interest. Ethical Approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed Consent Informed consent was obtained from all individual participants included in the study.

Introduction: Systemic chemotherapy is able to convert colorectal liver metastases (CRLM) that are initially unsuitable for local treatment into locally treatable disease. Surgical resection further improves survival in these patients. Our aim was to evaluate disease-free survival (DFS), overall survival, and morbidity for patients with CRLM treated with RFA following effective downstaging by chemotherapy, and to identify factors associated with recurrence and survival., Materials and Methods: Included patients had liver-dominant CRLM initially unsuitable for local treatment but eligible for RFA or RFA with resection after downstaging by systemic chemotherapy. Chemotherapeutic regimens consisted predominantly of CapOx, with or without bevacizumab. Follow-up was conducted with PET-CT or thoraco-pelvic CT., Results: Fifty-one patients had a total of 325 CRLM (median = 7). Following chemotherapy, 183 lesions were still visible on CT (median = 3). Twenty-six patients were treated with RFA combined with resection. During surgery, 309 CRLM were retrieved on intraoperative ultrasound (median = 5). Median survival was 49 months and was associated with extrahepatic disease at time of presentation and recurrences after treatment. Estimated cumulative survival at 1, 3 and 4 years was 90, 63 and 45 %, respectively. Median DFS was 6 months. Twelve patients remained free of recurrence after a mean follow-up of 32.6 months., Conclusion: RFA of CRLM after conversion chemotherapy provides potential local control and a good overall survival. To prevent undertreatment, the involvement of a multidisciplinary team in follow-up imaging and assessment of local treatment possibilities after palliative chemotherapy for liver-dominant CRLM should always be considered.

Objective: The extracellular matrix (ECM) of ovarian cancer may provide a number of potential biomarkers. Chondroitin sulfate (CS), a class of sulfated polysaccharides, is abundantly present in the ECM of ovarian cancer. Structural alterations of CS chains (i.e. sulfation pattern) have been demonstrated to play a role in cancer development and progression. In this study we investigate the potential of highly sulfated CS as a biomarker in ovarian cancer using the single chain antibody GD3A11 selected by the phage display technology., Methods: The specificity of the antibody was determined by an indirect ELISA. GD3A11 epitope expression was assessed by immunohistochemistry in healthy organs, benign and malignant ovarian tumors (N=359) and correlated to clinical parameters. The CHST15 gene, responsible for the biosynthesis of highly sulfated CS was evaluated for mutation and methylation status., Results: The GD3A11 epitope was minimally expressed in normal organs. Intense expression was observed in the ECM of different ovarian cancer subtypes, in contrast to benign ovarian tumors. Expression was independent of tumor grade, FIGO stage, and the use chemotherapy. For the aggressive ovarian cancer phenotype, intense expression was identified as an independent predictor for poor prognosis. CHST15 gene analysis showed no mutations nor an altered methylation status., Conclusion: Specific highly sulfated CS motifs expressed in the tumoral ECM hold biomarker potential in ovarian cancer patients. These matrix motifs constitute a novel class of biomarkers with prognostic significance and may be instrumental for innovative diagnostic and therapeutic applications (e.g. targeted therapy) in management of ovarian cancer., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Irreversible electroporation (IRE) is a novel image-guided tumor ablation technique that has shown promise for the ablation of lesions in proximity to vital structures such as blood vessels and bile ducts. The primary aim of the COLDFIRE-2 trial is to investigate the efficacy of IRE for unresectable, centrally located colorectal liver metastases (CRLM). Secondary outcomes are safety, technical success, and the accuracy of contrast-enhanced (ce)CT and (18)F-FDG PET-CT in the detection of local tumor progression (LTP)., Methods/design: In this single-arm, multicenter phase II clinical trial, twenty-nine patients with (18)F-FDG PET-avid CRLM ≤ 3,5 cm will be prospectively included to undergo IRE of the respective lesion. All lesions must be unresectable and unsuitable for thermal ablation due to vicinity of vital structures. Technical success is based on ceMRI one day post-IRE. All complications related to the IRE procedure are registered. Follow-up consists of (18)F-FDG PET-CT and 4-phase liver CT at 3-monthly intervals during the first year of follow-up. Treatment efficacy is defined as the percentage of tumors successfully eradicated 12 months after the initial IRE procedure based on clinical follow-up using both imaging modalities, tumor marker and (if available) histopathology. To determine the accuracy of (18)F-FDG PET-CT and ceCT, both imaging modalities will be individually scored by two reviewers that are blinded for the final oncologic outcome., Discussion: To date, patients with a central CRLM unsuitable for resection or thermal ablation have no curative treatment option and are given palliative chemotherapy. For these patients, IRE may prove a life-saving treatment option. The results of the proposed trial may represent an important step towards the implementation of IRE for central liver tumors in the clinical setting., Trial Registration Number: NCT02082782.

Image-guided tumor ablation techniques have significantly broadened the treatment possibilities for primary and secondary hepatic malignancies. A new ablation technique, irreversible electroporation (IRE), was recently added to the treatment armamentarium. As opposed to thermal ablation, cell death with IRE is primarily induced using electrical energy: electrical pulses disrupt the cellular membrane integrity, resulting in cell death while sparing the extracellular matrix of sensitive structures such as the bile ducts, blood vessels, and bowel wall. The preservation of these structures makes IRE attractive for colorectal liver metastases (CRLM) that are unsuitable for resection and thermal ablation owing to their anatomical location. This review discusses different technical and practical issues of IRE for CRLM: the indications, patient preparations, procedural steps, and different "tricks of the trade" used to improve safety and efficacy of IRE. Imaging characteristics and early efficacy results are presented. Much is still unknown about the exact mechanism of cell death and about factors playing a crucial role in the extent of cell death. At this time, IRE for CRLM should only be reserved for small tumors that are truly unsuitable for resection or thermal ablation because of abutment of the portal triad or the venous pedicles., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Irreversible electroporation (IRE) is a novel image-guided ablation technique that is rapidly gaining popularity in the treatment of malignant liver tumors located near large vessels or bile ducts. We describe a 28-year-old female patient with a 5 cm large, centrally located hepatocellular adenoma who wished to get pregnant. Regarding the risk of growth and rupture of the adenoma caused by hormonal changes during pregnancy, treatment of the tumor was advised prior to pregnancy. However, due to its central location, the tumor was considered unsuitable for resection and thermal ablation. Percutaneous CT-guided IRE was performed without complications and led to rapid and impressive tumor shrinkage. Subsequent pregnancy and delivery went uncomplicated. This case report suggests that the indication for IRE may extend to the treatment of benign liver tumors that cannot be treated safely otherwise.

Irreversible electroporation (IRE) is a novel image-guided ablation technique that is increasingly used to treat locally advanced pancreatic carcinoma (LAPC). We describe a 67-year-old male patient with a 5 cm stage III pancreatic tumor who was referred for IRE. Because the ventral approach for electrode placement was considered dangerous due to vicinity of the tumor to collateral vessels and duodenum, the dorsal approach was chosen. Under CT-guidance, six electrodes were advanced in the tumor, approaching paravertebrally alongside the aorta and inferior vena cava. Ablation was performed without complications. This case describes that when ventral electrode placement for pancreatic IRE is impaired, the dorsal approach could be considered alternatively.

Objective: Endometrial carcinomas are divided into type I endometrioid endometrial carcinomas (EECs), thought to arise from hyperplastic endometrium, and type II nonendometrioid endometrial carcinomas, thought to arise from atrophic endometrium. However, a minority (20%) of EECs have atrophic background endometrium, which was shown to be a marker of a worse prognosis. This study compares the immunohistochemical and genetic profiles of this possible third type to that of the known two types., Methods: 43 patients with grade 1 EEC and hyperplastic background endometrium (type I), 43 patients with grade 1 EEC and atrophic background endometrium (type III) and 21 patients with serous carcinoma (type II) were included (n=107). Tissue microarrays of tumor samples were immunohistochemically stained for PTEN, L1CAM, ER, PR, p53, MLH1, PMS2, β-catenin, E-cadherin and MIB1. The BRAF, KRAS, and PIK3CA genes were analyzed for mutations., Results: A significantly higher expression of ER and PR, and a lower expression of L1CAM, p53 and MLH1 were found in type I and III compared to type II carcinomas. Expression of E-cadherin was significantly reduced in type III compared to type I carcinomas. Mutation analysis showed significantly less mutations of KRAS in type III compared to type I and II carcinomas (p<0.01)., Conclusion: There appear to be slight immunohistochemical and genetic differences between EECs with hyperplastic and atrophic background endometrium. Carcinogenesis of EEC in atrophic endometrium seems to be characterized by loss of E-cadherin and a lack of KRAS mutations. As expected, endometrioid and serous carcinomas were immunohistochemically different., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Transcatheter computed tomography (CT) arterial portography-guided percutaneous liver tumor ablation has been proved to be feasible and accurate in treating liver metastases from colorectal origin that are obscure on ultrasound and unenhanced CT. However, distinguishing local recurrence from scars after ablation can still be difficult. This report describes nine patients with recurrences after ablation in whom transcatheter CT hepatic arteriography allowed differentiation of recurring and residual tumor tissue (incomplete ring enhancing lesion) from tumor-free nonenhancing scars. Using CT hepatic arteriography, it is possible to plan and guide percutaneous retreatment and confirm technical success without performing oversized repeat ablations or jeopardizing patients renal function., (Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.)