Assessment of DICOM Viewers Capable of Loading Patient-specific 3D Models Obtained by Different Segmentation Platforms in the Operating Room

Patient-specific 3D models obtained by the segmentation of volumetric diagnostic images play an increasingly important role in surgical planning. Surgeons use the virtual models reconstructed through segmentation to plan challenging surgeries. Many solutions exist for the different anatomical districts and surgical interventions. The possibility to bring the 3D virtual reconstructions with native radiological images in the operating room is essential for fostering the use of intraoperative planning. To the best of our knowledge, current DICOM viewers are not able to simultaneously connect to the picture archiving and communication system (PACS) and import 3D models generated by external platforms to allow a straight integration in the operating room. A total of 26 DICOM viewers were evaluated: 22 open source and four commercial. Two DICOM viewers can connect to PACS and import segmentations achieved by other applications: Synapse 3D® by Fujifilm and OsiriX by University of Geneva. We developed a software network that converts diffuse visual tool kit (VTK) format 3D model segmentations, obtained by any software platform, to a DICOM format that can be displayed using OsiriX or Synapse 3D. Both OsiriX and Synapse 3D were suitable for our purposes and had comparable performance. Although Synapse 3D loads native images and segmentations faster, the main benefits of OsiriX are its user-friendly loading of elaborated images and it being both free of charge and open source.     

Recognition of beta 2-microglobulin-negative (beta 2m-) T-cell blasts by natural killer cells from normal but not from beta 2m- mice: nonresponsiveness controlled by beta 2m- bone marrow in chimeric mice.

The role of major histocompatibility complex (MHC) class I expression in control of the sensitivity of normal cells to natural killer (NK) cells was studied by the use of mutant mice made deficient for expression of beta 2-microglobulin (beta 2m) through homologous recombination in embryonal stem cells. T-cell blasts from beta 2m-deficient (beta 2m -/-) mice were killed by NK cells from normal mice in vitro, while beta 2m +/- blasts were resistant. The beta 2m defect also affected the NK effector cell repertoire: NK cells from beta 2m -/- mice failed to kill beta 2m -/- blasts, while they retained the ability to kill the prototype NK cell target lymphoma YAC-1, although at reduced levels. The inability to recognize beta 2m -/- blasts could be transferred with beta 2m -/- bone marrow to irradiated beta 2m-expressing mice. In contrast, the development of CD8+ T cells (deficient in beta 2m -/- mice) was restored in such chimera. These results indicate that loss of MHC class I/beta 2m expression is sufficient to render normal cells sensitive to NK cells, and that the same defect in the hemopoietic system of a mouse renders its NK cells tolerant to beta 2m-deficient but otherwise normal cells. In the beta 2m -/- mice, NK cells may be selected or educated by other bone marrow cells to tolerate the MHC class I deficiency. Alternatively, the specificity may be controlled directly by the class I molecules on the NK cells themselves.     

Predictive biomarkers for the treatment of resectable esophageal and esophago-gastric junction adenocarcinoma: from hypothesis generation to clinical validation

Introduction: Esophageal and esophago-gastric junction (EGJ) adenocarcinomas remain a major health problem worldwide with a worryingly increasing incidence. Recent trials indicate survivals benefit for preoperative or perioperative chemoradiotherapy compared to surgery alone. Beside standard chemoradiotherapy regimens, new therapeutic approaches with targeted therapies have been proposed for the treatment of resectable disease. However, clinical outcomes remain extremely poor due to drug resistance phenomena. The failure of these approaches could be partially ascribed to their incorrect application in patients. Therefore, the identification of strong biomarkers for optimal patient management is urgently needed.

Areas covered: This review aims to summarize and critically discuss the most relevant findings regarding predictive biomarker development for neoadjuvant treatment of resectable esophageal and esophago-gastric junction adenocarcinoma patients.

Expert commentary: Optimizing the currently available therapeutic modalities through a more accurate selection of patients may avoid the use of ineffective and potentially toxic treatments. During the last decade, the advent of high-throughput ‘-omics’ technologies has set the basis for a new biomarker discovery approach from ‘molecule by molecule’ screening towards a large-scale systematic screening process with exponential increases in putative biomarkers, which often failed to provide adequate clinical validation.     

Postinfectious onset in functional dyspepsia is a risk factor for weight loss

Journal of Gastroenterology - Functional dyspepsia (FD) is differentiated into two subgroups: the postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). Acute gastroenteritis and...     

Recombinant human thyrotropin reduces serum vascular endothelial growth factor levels in patients monitored for thyroid carcinoma even in the absence of thyroid tissue

In this study, we have investigated in vivo the time-dependent effects of TSH on vascular endothelial growth factor (VEGF) production in patients monitored for thyroid carcinoma. Serum VEGF, thyroglobulin (Tg), and TSH levels were assayed at baseline and 6, 24, 30, 48, 72, and 96 h and 1 wk after administration of recombinant human TSH (rhTSH) in 45 thyroidectomized patients affected by differentiated thyroid carcinoma. At baseline, the patients with metastasis (18 cases) showed serum Tg and VEGF values significantly higher than those seen in the cured patients (27 cases). During rhTSH stimulation, the mean VEGF levels decreased significantly in both patient groups. In 60% of patients with metastasis, VEGF nadir occurred at the same time as serum TSH reached the highest values, whereas in 85.7% of the cured patients VEGF decreased after the TSH peak (P = 0.003). In conclusion, we demonstrate for the first time that short-term administration of rhTSH in patients monitored for differentiated thyroid carcinoma induces a significant reduction in serum VEGF values even in the absence of thyroid tissue. This result would suggest that TSH may be able in vivo to regulate VEGF production from tissues other than the thyroid gland.     

Adenosine receptors in regulation of dendritic cell differentiation and function

Differentiation of functional dendritic cells (DCs) critically depends on the microenvironment. DCs differentiate in hypoxic tumor sites and inflamed or damaged tissue. Because local concentrations of adenosine reach high physiologically relevant levels in these conditions, we assessed the expression of adenosine receptors and the effect of their activation on differentiation of human monocytes and mouse peritoneal macrophages and hematopoietic progenitor cells (HPCs) into myeloid DCs. Stimulation of adenosine receptors skews DC differentiation toward a distinct cell population characterized by expression of both DC and monocyte/macrophage cell surface markers. Pharmacologic analysis and experiments with cells from A(2B) adenosine receptor knockout mice identified A(2B) receptor as the mediator of adenosine effects on DCs. Unlike normal myeloid DCs, adenosine-differentiated DCs have impaired allostimulatory activity and express high levels of angiogenic, pro-inflammatory, immune suppressor, and tolerogenic factors, including VEGF, IL-8, IL-6, IL-10, COX-2, TGF-beta, and IDO. They promoted tumor growth if injected into tumors implanted in mice. Using adenosine desaminase knockout animals, we showed that DCs with proangiogenic phenotype are highly abundant under conditions associated with elevated levels of extracellular adenosine in vivo. Adenosine signaling through A(2B) receptor is an important factor of aberrant DC differentiation and generation of tolerogenic, angiogenic, and proinflammatory cells.