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Giant cell tumor of bone (GCTB) is a locally aggressive primary bone neoplasm composed by tumoral stromal cells (SCs) and a reactive component that consists of monocytic/histiocytic cells that give rise by fusion to osteoclast‐like multinucleated cells. Recently, specific Histone 3.3 mutations have been demonstrated in SCs of GCTB. Many of the pathways related to bone proliferation and regulation depend on the primary cilium, a microtubule‐based organelle that protrudes outside the cell and acts as a sensorial antenna. In the present work, we aimed to study the presence and role of primary cilia in GCTB. Ultrastructural, immunohistochemical, and immunofluorescence studies were performed in order to demonstrate, for the first time, that the primary cilium is located in spindle‐shaped SCs of GCTB. Moreover, we showed Hedgehog (Hh) signaling pathway activation in these cells. Hence, primary cilia may play a relevant role in GCTB tumorogenesis through Hh signaling activation in SCs. Research Highlights: Transmission electron microscopy allows describing and differentiating cellular subpopulations in giant cell tumor of bone (GCTB).The primary cilium is present in some tumoral stromal cells of GCTB.Hedgehog signalling is activated in these cells. [ABSTRACT FROM AUTHOR]

Abstract Background Efficient and safe transection of biological tissue in liver surgery is strongly dependent on the ability to address both parenchymal division and hemostasis simultaneously. In addition to the conventional clamp crushing or finger fracture methods other techniques based on radiofrequency (RF) currents have been extensively employed to reduce intraoperative blood loss. In this paper we present our broad research plan for a new RF-assisted device for bloodless, rapid resection of the liver. Methods Our research plan includes computer modeling and in vivo studies. Computer modeling was based on the Finite Element Method (FEM) and allowed us to estimate the distribution of electrical power deposited in the tissue, along with assessing the effect of the characteristics of the device on the temperature profiles. Studies based on in vivo pig liver models provided a comparison of the performance of the new device with other techniques (saline-linked technology) currently employed in clinical practice. Finally, the plan includes a pilot clinical trial, in which both the new device and the accessory equipment are seen to comply with all safety requirements. Results The FEM results showed a high electrical gradient around the tip of the blade, responsible for the maximal increase of temperature at that point, where temperature reached 100°C in only 3.85 s. Other hot points with lower temperatures were located at the proximal edge of the device. Additional simulations with an electrically insulated blade produced more uniform and larger lesions (assessed as the 55°C isotherm) than the electrically conducting blade. The in vivo study, in turn, showed greater transection speed (3 ± 0 and 3 ± 1 cm2/min for the new device in the open and laparoscopic approaches respectively) and also lower blood loss (70 ± 74 and 26 ± 34 mL) during transection of the liver, as compared to saline-linked technology (2 ± 1 cm2/min with P = 0.002, and 527 ± 273 mL with P = 0.001). Conclusion A new RF-assisted device for bloodless, rapid liver resection was designed, built and tested. The results demonstrate the potential advantages of this device over others currently employed.

Abstract Background Radiofrequency ablation (RFA) of tumors by means of internally cooled electrodes (ICE) combined with interstitial infusion of saline may improve clinical results. To date, infusion has been conducted through outlets placed on the surface of the cooled electrode. However, the effect of infusion at a distance from the electrode surface is unknown. Our aim was to assess the effect of perfusion distance (PD) on the coagulation geometry and deposited power during RFA using ICE. Methods Experiments were performed on excised bovine livers. Perfusion distance (PD) was defined as the shortest distance between the infusion outlet and the surface of the ICE. We considered three values of PD: 0, 2 and 4 mm. Two sets of experiments were considered: 1) 15 ablations of 10 minutes (n ≥ 4 for each PD), in order to evaluate the effect of PD on volume and diameters of coagulation; and 2) 20 additional ablations of 20 minutes. The effect of PD on deposited power and relative frequency of uncontrolled impedance rises (roll-off) was evaluated using the results from the two sets of experiments (n ≥ 7 for each PD). Comparisons between PD were performed by analysis of variance or Kruskal-Wallis test. Additionally, non-linear regression models were performed to elucidate the best PD in terms of coagulation volume and diameter, and the occurrence of uncontrolled impedance rises. Results The best-fit least square functions were always obtained with quadratic curves where volume and diameters of coagulation were maximum for a PD of 2 mm. A thirty per cent increase in volume coagulation was observed for this PD value compared to other values (P < 0.05). Likewise, the short coagulation diameter was nearly twenty five per cent larger for a 2 mm PD than for 0 mm. Regarding deposited power, the best-fit least square function was obtained by a quadratic curve with a 2 mm PD peak. This matched well with the higher relative frequency of uncontrolled impedance rises for PD of 0 and 4 mm. Conclusion Saline perfusion at around 2 mm from the electrode surface while using an ICE in RFA improves deposition of energy and enlarges coagulation volume.

Santiago Ramón y Cajal discovered a new type of cell related to the myenteric plexus and also to the smooth muscle cells of the circular muscle layer of the intestine. Based on their morphology, relationships and staining characteristics, he considered these cells as primitive neurons. One century later, despite major improvements in cell biology, the interstitial cells of Cajal (ICCs) are still controversial for many researchers. The aim of our study was to perform an immunohistochemical and ultrastructural characterization of the ICCs in the rabbit duodenum. We have found interstitial cells that are positive for c-Kit, CD34 and nestin and are also positive for Ki67 protein, tightly associated with somatic cell proliferation. By means of electron microscopy, we describe ICCs around enteric ganglia.They present triangular or spindle forms and a very voluminous nucleus with scarce perinuclear chromatin surrounded by a thin perinuclear cytoplasm that expands with long cytoplasmic processes. ICC processes penetrate among the smooth muscle cells and couple with the processes of other ICCs located in the connective tissue of the circular muscle layer and establish a three-dimensional network. Intercellular contacts by means of gap-like junctions are frequent. ICCs also establish gap-like junctions with smooth muscle cells.We also observe a population of interstitial cells of stellate morphology in the connective tissue that surrounds the muscle bundles in the circular muscle layer, usually close to nervous trunks. These cells establish different types of contacts with the muscle cells around them. In addition, the presence of a single cilium showing a structure 9 + 0 in an ICC is demonstrated for the first time. In conclusion, we report positive staining for c-kit , CD34, nestin and Ki 67. ICCs fulfilled the usual transmission electron microscopy (TEM) criteria. A new ultrastructural characteristic of at least some ICCs is demonstrated: the presence of a single cilium. Some populations of ICCs in the rabbit duodenum present certain immunohistochemical and ultrastructural characteristics that often are present in progenitor cells. [ABSTRACT FROM AUTHOR]

Summary background data. Radiofrequency ablation (RFA) is a relatively new technology for the local destruction of liver tumors. Development of recent devices has enabled the creation of larger lesions. Nevertheless, treating liver tumors larger than 2.5 cm in diameter often requires multiple overlapping ablations to encompass the tumor and the surrounding healthy tissue rim with an increasing risk of local recurrence.Material and methods. RFA (480 kHz) of the liver using our method was undertaken on a total number of 15 healthy farm pigs with (Group B, n = 8) or without (Group A, n = 5) the Pringle maneuver via laparotomy. The pigs were followed and euthanized on the seventh day of the experiment. Livers were removed for histological assessment. Time of the procedure, impedance, current, power output, energy output, temperatures in the liver, central temperature of the animal, volume size of the lesion, and delivered energy per lesion volume were determined and compared among groups. Additionally a regularity ratio (RR) was determined by gross examination of the specimen and scored (0–3) taking into account regularity and predictability of the ablation with pathologic assessment.Results. With both methods, ellipsoid lesions were created between the two probes. In both groups tissue impedance fell with time (r = −0.47, P < 0.01 and r = −0.34, P < 0.05, in Groups A and B, respectively). The mean lesion size achieved with the Pringle maneuver was the largest lesion size described in the literature for any RFA method in vivo and was greater in Group B than in Group A (123.22 cm3 ± 49.62 and 52.40 cm3 ± 23.59, respectively, P < 0.05). A better regularity and predictability evaluated by RR was observed in Group B compared to Group A (1.88 ± 1.35 and 0.40 ± 0.55, respectively, P < 0.05). Five major complications were described and attributed primarily to failure in isolation from hypertermic lesions.Conclusions. Our new bipolar saline-enhanced electrode with Pringle maneuver achieves large hepatic ablations in in vivo pig liver. These large lesions are well-tolerated by the animal when thermal injuries to adjacent structures are avoided. [Copyright &y& Elsevier]