Propensity score matching demonstrates similar results for radiofrequency ablation compared to surgical resection in colorectal liver metastases.

PURPOSE: Minimally invasive ablative treatments, such as radiofrequency ablation (RFA), are increasingly used in the curative treatment of patients with colorectal liver metastases (CRLM). Selection bias plays an important role in the evaluation of early and late results between RFA and surgery. The purpose of this study was to evaluate recurrences and oncological survival following these two treatment modalities using single pair propensity score matching. METHODS: Between 2000 and 2018, patients curatively treated for CRLM were included in a multicentre database. Patients were excluded when receiving two-staged treatment, synchronous treatment with primary tumor or combination of modalities. Propensity score matching was used to minimize influence of known covariates, i.e., age, ASA, FONG CRS, location and T-stage of the primary tumor. RESULTS: Before matching, the RFA group contained 39 patients and the surgery group 982 patients, after matching both groups contained 36 patients. After matching, mean age was 69 years (53-86) for RFA and 68 (50-86) for surgery, with a mean tumor size of respectively 2.5 cm (0.8-6.5) and 3.4 cm (1-7.5). Both groups showed similar complication rate according to Clavien-Dindo (17vs.33%; p = 0.18), recurrence rate (58vs.64%; p = 0.09) without significant differences in 5-year DFS and OS (RFA compared to surgery respectively 25vs.37%; p = 0.09 and 42vs.53%; p = 0.09). CONCLUSION: After propensity score matching, RFA showed lower complications and similar oncological survival compared to surgical resection. In patients who are suboptimal candidates for surgery, RFA seems to be a good and safe alternative.

Software-based planning of ultrasound and CT-guided percutaneous radiofrequency ablation in hepatic tumors.

OBJECTIVES: Radiofrequency ablation (RFA) can be associated with local recurrences in the treatment of liver tumors. Data obtained at our center for an earlier multinational multicenter trial regarding an in-house developed simulation software were re-evaluated in order to analyze whether the software was able to predict local recurrences. METHODS: Twenty-seven RFA ablations for either primary or secondary hepatic tumors were included. Colorectal liver metastases were shown in 14 patients and hepatocellular carcinoma in 13 patients. Overlap of the simulated volume and the tumor volume was automatically generated and defined as positive predictive value (PPV) and additionally visually assessed. Local recurrence during follow-up was defined as gold standard. Sensitivity and specificity were calculated using the visual assessment and gold standard. RESULTS: Mean tumor size was 18 mm (95% CI 15-21 mm). Local recurrence occurred in 5 patients. The PPV of the simulation showed a mean of 0.89 (0.84-0.93 95% CI). After visual assessment, 9 incomplete ablations were observed, of which 4 true positives and 5 false positives for the detection of an incomplete ablation. The sensitivity and specificity were, respectively, 80% and 77% with a correct prediction in 78% of cases. No significant correlation was found between size of the tumor and PPV (Pearson Correlation 0.10; p = 0.62) or between PPV and recurrence rates (Pearson Correlation 0.28; p = 0.16). CONCLUSIONS: The simulation software shows promise in estimating the completeness of liver RFA treatment and predicting local recurrence rates, but could not be performed real-time. Future improvements in the field of registration could improve results and provide a possibility for real-time implementation.

Does perfusion computed tomography correlate to pathology in colorectal liver metastases?

INTRODUCTION: Targeted therapy against tumor angiogenesis is widely used in clinical practice for patients with colorectal liver metastases (CRLM). Possible predictive biomarkers for tumor angiogenesis, such as, microvessel density (MVD), hypoxia and cell proliferation, can be determined using immunohistochemical staining. However, patients ineligible for surgical treatment need to undergo invasive diagnostic interventions in order to determine these biomarkers. CT perfusion (CTP) is an emerging functional imaging technique, which can non-invasively determine vascular properties of solid tumors. The purpose of this study was to evaluate CTP with histological biomarkers in CRLM. MATERIAL AND METHODS: Patients with CRLM underwent CTP one day before liver surgery. CTP analysis was performed on the entire volume of the largest metastases in each patient. Dual-input maximum slope analysis was used and data concerning arterial flow (AF), portal flow (PF) and perfusion index (PI) were recorded. Immunohistochemical staining with CD34, M75/CA-IX and MIB-1 was performed on the rim in the midsection of the tumor to determine respectively MVD, hypoxia and cell proliferation. RESULTS: Twenty CRLM in 20 patients were studied. Mean size of the largest CRLM was 37 mm (95% CI 21-54 mm). Mean AF and PF were respectively 64 ml/min/100ml (95% CI 48-79) and 30 ml/min/100ml (95% CI 22-38). Mean PI was 68% (95% CI 62-73). No significant correlation was found between tumor growth patterns and CTP (p = 0.95). MVD did not significantly correlate to AF (r = 0.05; p = 0.84), PF (r = 0.17; p = 0.47) and PI (r = -0.12; p = 0.63). Cell proliferation also did not significantly correlate to AF (r = 0.07; p = 0.78), PF (r = -0.01; p = 0.95) and PI (r = 0.15; p = 0.52). Hypoxia did not significantly correlate to AF (r = -0.05; p = 0.83), however, significantly to PF (r = 0.51; p = 0.02) and a trend to negative correlation with PF (r = -0.43; p = 0.06). However, after controlling the false discovery rate, no significant correlation between CTP and used immunohistochemical biomarkers was found. CONCLUSION: In conclusion, this feasibility study found a trend to negative correlation between PI and hypoxia, CTP might therefore possibly evaluate this prognostic marker in CRLM non-invasively. However, CTP is not an appropriate technique for the assessment of microvessels or cell proliferation in CRLM.

Results after simultaneous surgery and RFA liver ablation for patients with colorectal carcinoma and synchronous liver metastases.

BACKGROUND: Approximately 20% of patients with colorectal cancer present with synchronous liver metastases (sCRLM). These patients can be treated with a "one-step procedure" or staged resection, with or without radiofrequency ablation (RFA). Colorectal surgery in combination with intraoperative RFA leads to concerns regarding postoperative complications and survival. The purpose was to evaluate the one-step procedure with or without RFA in patients with sCRLM. MATERIALS AND METHODS: Between January 2000 and September 2018, patients with sCRLM were selected in two tertiary referral centers and retrospectively analyzed. Postoperative morbidity and survival were analyzed. RESULTS: From a total of 410 patients presenting with sCRLM, 329 patients underwent a staged resection and 81 a one-step procedure. The 3-year overall survival (OS) was respectively 66% and 69% for one-step procedure and staged resection (P = 0.24). A total of 18 patients underwent RFA during the one step procedure. No significant differences were shown in postoperative complications whether intraoperative RFA was used in patients with sCRLM. In the one-step procedure, the 3-year OS was respectively 43% and 72% wheter patients did or did not receive RFA (P = 0.19). CONCLUSION: OS for patients with sCRLM was similar for both one-step procedure and staged resection. Intraoperative RFA for sCRLM is technically safe.

Short term and long term results of patients with colorectal liver metastases undergoing surgery with or without radiofrequency ablation.

PURPOSE: The combination of resection and radiofrequency ablation (RFA) may provide an alternative treatment for patients with unresectable colorectal liver metastases (CRLM). Although the results in literature look promising, uncertainty exists with regard to complication risks and survival for this therapy. METHODS: From January 2000 to May 2013, patients were included in a prospective multicenter database when treated for CRLM. Exclusion criteria were: two-staged treatment, synchronous resection of liver metastases and primary tumor, loss to follow-up or extrahepatic metastases. Patients were divided in a resection-only group (ROG) and combination group (CG). Outcome variables were retrospectively analyzed. RESULTS: In CG, 98 patients were included versus 534 patients in ROG. There were no differences in general patient characteristics. Patients in CG had a higher Fong clinical risk score (CRS; P = 0.001), better ASA classification (P = 0.04) and received more neoadjuvant chemotherapy (P = 0.001). There was no difference in postoperative morbidity or 90-day mortality. The 5-year disease-free survival (DFS) for CG and ROG was 25% and 36.1% (P = 0.03), respectively. For the 5-year overall survival (OS) this was respectively 42% and 62.2% (P = 0.001). On multivariate analysis, Fong CRS was a significant predictor for DFS. For OS, Fong CRS, ASA class IV and the combination therapy were significant predictors. CONCLUSION: The combination of hepatic resection and intraoperative RFA is a safe procedure, without increase in postoperative morbidity or mortality. Combining RFA and resection in one session is a valid treatment option for patients who would otherwise be inoperable.

Bone marrow-derived myofibroblasts contribute functionally to scar formation after myocardial infarction.

Myofibroblasts play a major role in scar formation during wound healing after myocardial infarction (MI). Their origin has been thought to be interstitial cardiac fibroblasts. However, the bone marrow (BM) can be a source of myofibroblasts in a number of organs after injury. We have studied the temporal, quantitative and functional role of BM-derived (BMD) myofibroblasts in myocardial scar formation. MI was induced by permanent coronary artery ligation in mice reconstituted with EGFP or pro-Col1A2 transgenic BM. In the latter, luciferase and beta-galactosidase transgene expression mirrors that of the endogenous pro-collagen 1A2 gene, which allows for functional assessment of the recruited cells. After MI, alpha-SMA-positive myofibroblasts and collagen I gradually increased in the infarct area until day 14 and remained constant afterwards. Numerous EGFP-positive BMD cells were present during the first week post-MI, and gradually decreased afterwards until day 28. Peak numbers of BMD myofibroblasts, co-expressing EGFP and alpha-SMA, were found on day 7 post-MI. An average of 21% of the BMD cells in the infarct area were myofibroblasts. These cells constituted up to 24% of all myofibroblasts present. By in vivo IVIS imaging, BMD myofibroblasts were found to be active for collagen I production and their presence was confined to the infarct area. These results show that BMD myofibroblasts participate actively in scar formation after MI.