Scale-adaptive supervoxel-based random forests for liver tumor segmentation in dynamic contrast-enhanced CT scans

Purpose

Toward an efficient clinical management of hepatocellular carcinoma (HCC), we propose a classification framework dedicated to tumor necrosis rate estimation from dynamic contrast-enhanced CT scans. Based on machine learning, it requires weak interaction efforts to segment healthy, active and necrotic liver tissues.

Methods

Our contributions are two-fold. First, we apply random forest (RF) on supervoxels using multi-phase supervoxel-based features that discriminate tissues based on their dynamic in response to contrast agent injection. Second, we extend this technique in a hierarchical multi-scale fashion to deal with multiple spatial extents and appearance heterogeneity. It translates in an adaptive data sampling scheme combining RF and hierarchical multi-scale tree resulting from recursive supervoxel decomposition. By concatenating multi-phase features across the hierarchical multi-scale tree to describe leaf supervoxels, we enable RF to automatically infer the most informative scales without defining any explicit rules on how to combine them.

Results

Assessment on clinical data confirms the benefits of multi-phase information embedded in a multi-scale supervoxel representation for HCC tumor segmentation.

Conclusion

Dedicated but not limited only to HCC management, both contributions reach further steps toward more accurate multi-label tissue classification.

     

Destruction of nonimmunogenic mammary tumor cells by a fusogenic oncolytic herpes simplex virus induces potent antitumor immunity.

In principle, destruction of tumor cells in vivo by oncolytic agents would release the entire repertoire of tumor antigens in their natural forms, leading to effective antitumor immunity. This goal has been elusive despite extensive testing of numerous strategies. We developed a doubly fusogenic oncolytic herpes simplex virus (Synco-2D) that kills tumor cells by a unique dual mechanism combining direct cytolysis with syncytial formation induced by cell membrane fusion. A single intratumor injection of Synco-2D induced strong antitumor immunity against an otherwise nonimmunogenic murine mammary tumor growing in immune-competent mice. CD8+ T cells were the primary mediators of immunity, contributing to the destruction of both primary and metastatic tumors. We conclude that the fusogenic capacity of Synco-2D enables it to elicit antitumor immunity exceeding that induced by more conventional oncolytic viruses.     

Thoracic skeletal anomalies following surgical treatment of esophageal atresia. Lessons from a national cohort

Introduction

Thoracotomy as surgical approach for esophageal atresia treatment entails the risk of deformation of the rib cage and consequently secondary thoracogenic scoliosis. The aim of our study was to assess these thoracic wall anomalies on a large national cohort and search for factors influencing this morbidity.

Solitary fibrous tumours and haemangiopericytoma of the meninges. A retrospective study for outcome and prognostic factor assessment

Background

To report on the outcome of patients diagnosed with central nervous system haemangiopericytoma (HPC) or solitary fibrous tumours (SFT) and identify factors that may influence recurrence and survival.

Bystander transfer of functional human CD40 ligand from gene-modified fibroblasts to B-chronic lymphocytic leukemia cells

CD40 ligand (CD40L) is a good candidate molecule for the immunotherapy of B cell malignancies including B-chronic lymphocytic leukemia (B-CLL), because it may increase the capacity of the malignant cells to present tumor antigens. However, efforts to manipulate expression of the human CD40L (hCD40L) molecule have foundered on problems associated with lack of consistent gene transfer into the malignant target cells. We now describe a new, highly reproducible method for inducing hCD40L surface expression on malignant B cells, which is dependent on intercellular transfer of the hCD40L protein from donor gene-modified fibroblasts to patient tumor cells. Ten B-CLL samples were cocultured with MRC-5 fibroblasts (a human embryonic lung cell line) previously transduced with an adenoviral vector encoding the hCD40L gene. The malignant cells expressed high levels of surface hCD40L, B7-1, B7-2, and ICAM-1 after coculture. Upregulation of B7-1 and B7-2 was cycloheximide inhibitable and was a consequence of CD40 activation. However, inhibition of protein synthesis had no effect on the ability of B-CLL cells to acquire surface expression of hCD40L. hCD40L surface expression required cell-to-cell contact, but was independent of CD40 engagement. hCD40L transfer was not mediated by membrane fusion. The transferred hCD40L was functionally intact and B-CLL cells expressing this molecule induced increased interferon-gamma production from autologous peripheral blood T lymphocytes. This approach does not use any direct gene transfer to primary leukemia cells and can readily be scaled up for production of clinical B-CLL vaccines.     

Targeted temperature management after intraoperative cardiac arrest: a multicenter retrospective study

Purpose

Few outcome data are available about temperature management after intraoperative cardiac arrest (IOCA). We describe targeted temperature management (TTM) (32–34 °C) modalities, adverse events, and association with 1-year functional outcome in patients with IOCA.

Methods

Patients admitted to 11 ICUs after IOCA in 2008–2013 were studied retrospectively. The main outcome measure was 1-year functional outcome.

Results

Of the 101 patients [35 women and 66 men; median age, 62 years (interquartile range, 42–72)], 68 (67.3%) were ASA PS I to III and 57 (56.4%) had emergent surgery. First recorded rhythms were asystole in 44 (43.6%) patients, pulseless electrical activity in 36 (35.6%), and ventricular fibrillation/tachycardia in 20 (19.8%). Median times from collapse to cardiopulmonary resuscitation and return of spontaneous circulation (ROSC) were 0 min (0–0) and 10 min (4–20), respectively. The 30 (29.7%) patients who received TTM had an increased risk of infection (P = 0.005) but not of arrhythmia, bleeding, or metabolic/electrolyte disorders. By multivariate analysis, one or more defibrillation before ROSC was positively associated with a favorable functional outcome at 1-year (OR 3.06, 95% CI 1.05–8.95, P = 0.04) and emergency surgery was negatively associated with 1-year favorable functional outcome (OR 0.36; 95% CI 0.14–0.95, P = 0.038). TTM use was not independently associated with 1-year favorable outcome (OR 0.82; 95% CI 0.27–2.46, P = 0.72).

Conclusions

TTM was used in less than one-third of patients after IOCA. TTM was associated with infection but not with bleeding or coronary events in this setting. TTM did not independently predict 1-year favorable functional outcome after IOCA in this study.

     

A Small Animal Positron Emission Tomography Study of the Effect of Chemotherapy and Hormonal Therapy on the Uptake of 2-Deoxy-2-[F-18]fluoro-<Emphasis Type="SmallCaps">d</Emphasis>-glucose in Murine Models of Breast Cancer

Purpose We used small animal positron emission tomography (PET) imaging to monitor the time-course of tumor metabolic response to hormone and chemotherapy in a murine model of hormone-sensitive breast cancer. Procedures Estrogen receptor positive murine mammary carcinomas were inoculated in Balb/c mice. Small animal PET imaging using 2-deoxy-2-[F-18]fluoro-d-glucose (FDG) was used to assess tumor metabolic activity. Imaging was done before and at days 1, 7, and 14 after the administration of doxorubicin, methotrexate, letrozole, or placebo. The tumor uptake of FDG was calculated from a region-of-interest drawn around the tumor. Results All treatments resulted in a decrease in tumor growth rate and end volume compared to untreated control. FDG uptake was also markedly decreased after treatment although a flare reaction was observed on PET at day 7, the intensity of which varied according to the treatment modality. Conclusion PET imaging is sensitive to detect early changes associated with therapy in murine breast cancer models. A flare reaction was observed 7 days after the initiation of therapy.