Usefulness of Imaging Response Assessment after Irreversible Electroporation of Localized Pancreatic Cancer-Results from a Prospective Cohort.

(1) Background: Irreversible electroporation (IRE) is a nonthermal ablation technique that is being studied in nonmetastatic pancreatic cancer (PC). Most published studies use imaging outcomes as an efficacy endpoint, but imaging interpretation can be difficult and has yet to be correlated with survival. The aim of this study was to examine the correlation of imaging endpoints with survival in a cohort of IRE-treated PC patients. (2) Methods: Several imaging endpoints were examined before and after IRE on 18F-fluorodeoxyglucose positron emission tomography (PET) with computed tomography. Separate analyses were performed at the patient and lesion levels. Mortality rate (MR) ratios for imaging endpoints after IRE were estimated. (3) Results: Forty-one patients were included. Patient-level analysis revealed that progressive disease (PD), as defined by RECIST 1.1, is correlated with a higher MR at all time intervals, but PD, as defined by EORTC PET response criteria, is only correlated with the MR in the longest interval. No correlation was found between PD, as defined by RECIST, and the MR in the lesion-level analysis. (4) Conclusions: Patient-level PD, as defined by RECIST, was correlated with poorer survival after IRE ablation, whereas no correlations were observed in the lesion-level analyses. Several promising lesion-level outcomes were identified.

Imaging response evaluation after local ablative treatments in locally advanced pancreatic cancer: an expedited systematic review.

BACKGROUND: Several local ablative modalities have been introduced for the treatment of locally advanced pancreatic cancer (LAPC). However, there is no consensus on how to evaluate the imaging response after treatment. A systematic review was performed regarding the use of imaging for response assessment in LAPC. METHODS: A systematic literature search was conducted in PubMed. Studies reporting imaging outcomes were included in the review. Studies were excluded if the imaging outcomes could not be differentiated between different disease stages, tumor histology or surgical approaches. RESULTS: Thirty-four studies were included in the analysis. Fourteen studies used standardized response criteria, while six studies did not report the response evaluation method. The rest used self-determined criteria, absolute size comparisons or similar methods. One study found a correlation between early systemic progression (<6 months) and overall survival. CONCLUSION: There was notable variation in the use of imaging for response assessment in LAPC. This significantly hinders cross-comparison of results among studies. There is currently only sparse evidence of an association between imaging responses and overall survival. The field calls for standardized recommendations regarding the choice of response assessment method, timing of scans, target definition and reporting of outcomes.

D-Dimer predicts prognosis and non-resectability in patients with pancreatic cancer: a prospective cohort study.

To examine the impact of plasma D-dimer levels in predicting 3-year survival and nonresectability in pancreatic cancer patients. Ninety-five patients were divided into three groups according to plasma D-dimer levels. Kaplan-Meier survival curves and hazard ratios were computed, and diagnostic indices of D-dimer in the prediction of resectability were assessed. The median survival among patients with low, medium and high D-dimer levels was 13.7 [95% confidence interval (CI): 10.2-19.6], 6.2 (95% CI: 2.0-15.1) and 2.4 months (95% CI: 1.4-3.3), respectively. The adjusted hazard ratio of death in the group of patients with high D-dimer levels was 2.2 (95% CI: 1.1-4.2). The positive and negative predictive values of D-dimer in the prediction of nonresectability were 89% (95% CI: 77-96%) and 48% (95% CI: 33- 63%), respectively. An elevated D-dimer level is associated with reduced survival in pancreatic cancer and predicts nonresectability.

Increased levels of citrullinated antithrombin in plasma of patients with rheumatoid arthritis and colorectal adenocarcinoma determined by a newly developed ELISA using a specific monoclonal antibody.

Citrullination is a post-translational modification that plays essential roles in both physiological processes and disease. Recent studies have found increased levels of citrullinated antithrombin in patients with rheumatoid arthritis and in different malignant tumours. Antithrombin, the main haemostatic serpin, loses its anticoagulant function via citrullination, which might contribute to the pathogenesis or thrombotic side effects of these disorders. We have developed a specific monoclonal antibody against citrullinated antithrombin. We determined the levels of citrullinated antithrombin and anti-FXa activity in plasma from 66 donors, 17 patients with rheumatoid arthritis and 77 patients with colorectal adenocarcinoma (42 suffering from venous thrombosis). Healthy subjects had negligible amounts of citrullinated antithrombin in plasma (7.9 ± 22.1 ng/ml), while it significantly increased in patients with rheumatoid arthritis or adenocarcinoma (159.7 ± 237.6 ng/ml and 36.8 ± 66.1 ng/ml), levels that, however, did not modify the plasma anticoagulant activity. Moreover, we did not find association between citrullinated antithrombin and the thrombotic risk in patients with adenocarcinoma. In conclusion, we have developed an antibody specific for citrullinated antithrombin that allows its quantification in biological samples, offering a new tool for the analysis of citrullination in different diseases. We confirm increased levels of citrullinated antithrombin in plasma of patients with rheumatoid arthritis and adenocarcinoma. This modification, probably local, could have pathological consequences in both disorders, but only affects a minor fraction of plasma antithrombin, resulting in no significant reduction of global anticoagulant activity. This result explains the absence of association of this marker with an increased risk of thrombosis in patients with colorectal adenocarcinoma.

Preoperative plasma D-dimer is a predictor of postoperative deep venous thrombosis in colorectal cancer patients: a clinical, prospective cohort study with one-year follow-up.

PURPOSE: The study examined if preoperative plasma D-dimer level was associated with the postoperative cumulative incidence of deep venous thrombosis in patients with colorectal cancer admitted for intended curative surgery. METHODS: In 176 consecutive patients with newly-diagnosed colorectal cancer and absence of preoperative deep venous thrombosis, we measured the preoperative plasma D-dimer levels and performed compression ultrasonography for deep venous thrombosis prior to surgery, as well as one week, one month, and one year after surgery. RESULTS: The cumulative incidence of deep venous thrombosis up to one year after surgery was 20 percent (95 percent confidence interval, 12 to 31 percent) in the positive D-dimer group compared with 5 percent (95 percent confidence interval, 2 to 12 percent) in the negative D-dimer group. The adjusted hazard ratio of deep venous thrombosis in the positive vs. the negative D-dimer group was 6.53 (95 percent confidence interval, 1.58 to 27.0). CONCLUSIONS: A positive preoperative D-dimer was associated with a higher cumulated incidence of postoperative deep venous thrombosis. D-dimer might be useful in identifying those colorectal cancer patients who fail to respond to standard prophylaxis for deep venous thrombosis.

Haemostatis activity in rectal cancer patients exposed to preoperative radiotherapy: a clinical prospective cohort study.

To investigate whether markers of haemostasis activity increased during preoperative radiotherapy and whether postoperative marker levels were increased in irradiated rectal cancer patients when compared with nonirradiated rectal and colon cancer patients. In 45 rectal cancer patients, we measured plasma levels of prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complex, and D-dimer during radiotherapy. Postoperative levels of F1 + 2, thrombin-antithrombin complex, and D-dimer in irradiated patients were compared with postoperative levels in 123 nonirradiated colon and rectal cancer patients. A small oscillation in F1 + 2 levels was observed during radiotherapy among long-term low-intensity radiotherapy recipients. Postoperative levels of F1 + 2 and D-dimer were significantly higher among patients who received short-term high-intensity radiotherapy. This study provided no evidence for activation of the haemostatic system during preoperative radiotherapy in patients with rectal cancer. Some evidence was provided for increased postoperative haemostatic activity among rectal cancer patients who received short-term high-intensity radiotherapy, when compared with patients who received long-term low-intensity radiotherapy, and nonirradiated patients.