Bone Micromorphology and Material Attrition After Sonic, Ultrasonic and Conventional Osteotomies.

BACKGROUND/AIM: Osteotomy as the first step in surgery, provides access to the field and its application could influence the outcome. Nowadays, the conventional burr reduction is being challenged by newer sonic and ultrasonic methods. We investigated the bone structural integrity and metal attrition residues both in bone and the irrigation fluid. MATERIALS AND METHODS: Bovine ribs were cut using three methods. Bone cuts were studied using Environmental Scanning Electron Microscopy (ESEM) for tissue discrepancies and Scanning Electron Microscopy/Energy Dispersion X-Ray Microanalysis (SEM/EDX) for organic and inorganic debris. RESULTS: Better preservation of bone architecture was seen in piezo and sono surgery while metal attrition was not conclusive (p>0.05). Unlike in bone analyses, both bur and ultrasonic osteotomies showed statistically significant higher median inorganic detection per analysis (p=0.021 and p=0.037, respectively). CONCLUSION: Sono and piezo surgery proved to be less invasive while attrition properties were the same.

[Granulomatous pleuritis and chylothorax caused by calcite inhalation in a Galgo Español dog]. / Granulomatöse Pleuritis und Chylothorax durch Kalzitinhalation bei einem Galgo Español.

A 6-year-old, male Galgo Español dog was presented with severe dyspnea. Radiography and ultrasonography revealed pleural effusion. Approximately 4 l of a milky and slightly reddish fluid were aspirated and drained from the thoracic cavity. Clinical chemistry examination of the fluid indicated a modified transudate with a high amount of triglycerides. On cytological examination, degenerated neutrophilic granulocytes, small lymphocytes, macrophages and chylomicrons were found. A chest tube was placed and computed tomography was performed, which indicated thickening of parietal and visceral pleura and enlargement of the sternal lymph node without abnormal findings in the lungs. During subsequent thoracoscopy disseminated proliferative masses, appearing as small white nodules, covering nearly the entire pleural surface were found and biopsies were taken for further analysis. Histopathologic diagnosis was a granulomatous pleuritis with intralesional birefringent foreign material. Energy dispensive x-ray emission analysis was used to determine the origin of the material. Scanning electron microscopy revealed high amounts of calcium containing foreign material (calcite) within the granulomas. An extended clinical history of the dog gave evidence that the animal had lived next to a construction site 15 months earlier and may well have inhaled the calcium-containing dust. Treatment with prednisolone was initiated, however the dog developed gastro-intestinal side effects and treatment was stalled after 10 weeks. Dyspnea and liquidothorax re-occurred 4 months later. A further attempt of immunosupressive treatment was commenced, using a combination of prednisolone and ciclosporine, which again was not tolerated by the patient. The dog finally developed pneumonia and was euthanized by the owner's request.

A Distinct Oncogenerative Multinucleated Cancer Cell Serves as a Source of Stemness and Tumor Heterogeneity.

The effects of anticancer treatments on cell heterogeneity and their proliferative potential play an important role in tumor persistence and metastasis. However, little is known about de-polyploidization, cell fate, and physiologic stemness of the resulting cell populations. Here, we describe a distinctive cell type termed "pregnant" P1 cells found within chemotherapy-refractory ovarian tumors, which generate and gestate daughter generation Gn cells intracytoplasmically. Release of Gn cells occurred by ejection through crevices in the P1 cell membrane by body contractions or using a funiculus-like structure. These events characterized a not yet described mechanism of cell segregation. Maternal P1 cells were principally capable of surviving parturition events and continued to breed and nurture Gn progenies. In addition, P1 cells were competent to horizontally transmit offspring Gn cells into other specific proximal cells, injecting them to receptor R1 cells via cell-cell tunneling. This process represents a new mechanism used by tumor cells to invade surrounding tissues and ensure life cycles. In contrast to the pregnant P1 cells with low expression of stem cell markers despite their physiologic stemness, the first offspring generations of daughter G1 cells expressed high levels of ovarian cancer stem cell markers. Furthermore, both P1 and Gn cells overexpressed multiple human endogenous retroviral envelope proteins. Moreover, programmed death-ligand 1 and the immunosuppressive domain of the retroviral envelope proteins were also overexpressed in P1 cells, suggesting effective protection against the host immune system. Together, our data suggest that P1 oncogenerative cancer cells exhibit a not yet described cell biological mechanism of persistence and transmission of malignant cells in patients with advanced cancers.Significance: P1 oncogenerative cell entities express low levels of CSC markers, which are characteristic of their histological origin. Cancer Res; 78(9); 2318-31. ©2018 AACR.

The asbestos fibre burden in human lungs: new insights into the chrysotile debate.

The traceability of asbestos fibres in human lungs is a matter of discussion especially for chrysotile. This issue is of high significance for differential diagnosis, risk assessment and occupational compensation. At present no intra-individual longitudinal information is available. This study addresses the question whether the asbestos fibre burden in human lungs decreases with time after exposure cessation.The database of the German Mesothelioma Register was screened for patients with asbestos body counts of at least 500 fibres per gram of wet lung, which had been analysed twice from different tissue excisions at minimum intervals of 4 years.Twelve datasets with individual longitudinal information were discovered with a median interval of about 8 years (range 4-21 years). Both examinations were performed after exposure cessation (median: surgery, 9.5 years; autopsy, 22 years). Pulmonary asbestos fibre burden was stable between both examinations (median 1623/4269 asbestos bodies per gram wet lung). Electron microscopy demonstrated a preponderance of chrysotile (median 80%).This study is the first to present longitudinal intra-individual data about the asbestos fibre burden in living human lungs. The high biopersistence of amphiboles, but also of chrysotile, offers mechanistic explanations for fibre toxicity, especially the long latency period of asbestos-related diseases.

Low-flow lower body perfusion for spinal protection in a frozen elephant trunk simulation model.

OBJECTIVES: The frozen elephant trunk (FET) procedure using isolated selective cerebral perfusion (SCP) at moderate hypothermia is associated with an increased risk for spinal cord ischaemia. The aim of this study was to evaluate the benefit of a combined selective cerebral and low-flow lower body perfusion (CLBP) in a porcine model. METHODS: Twenty pigs (46 ± 5 kg) were cooled on cardiopulmonary bypass (CPB) to 28°C. After aortic clamping and occlusion of the thoracic segmental arteries (TSAT4-T13), a pressure-controlled SCP (50 mmHg) was established for 90 min. Randomly, in n = 10 animals, an additional lower body perfusion (LBP) was performed with 15 ml/kg/min (CLBP). Regional spinal cord blood flow (SCBF), cerebrospinal fluid pressure (CSFP) and motor-evoked potentials (MEPs) were registered at six time points. The animals were sacrificed after 120 min of weaning from CPB, and the spinal cord was analysed histologically using a schematic scoring system (0 = normal, 8 = total necrosis). RESULTS: Isolated SCP led to an SCBF decrease from 18.5 ± 9.4 to 0.9 ± 1.4 ml/min/100 g in the L1-L5 region (P = 0.005). CLBP preserved an almost physiological lumbar SCBF of 11.3 ± 5.3 ml/min/100 g. CSFP decreased in both groups during cooling and SCP/CLBP to 70-80% and increased during reperfusion to 150%, without showing significant differences between groups. The MEP amplitude decreased in both groups, with certain regional differences: T7-T11. MEP recording revealed a more pronounced amplitude decrease in the CLBP group (52.5 ± 2.0 vs 71.3 ± 0.9%), but MEP amplitudes recovered in both groups (SCP: 73.7 ± 0.5 vs CLBP: 82.6 ± 0.1%). During selective hypothermic perfusion, SCP-treated animals showed significant lower MEP amplitudes, when compared with CLBP-treated animals: 60 ± 9 vs 90 ± 3% (P < 0.001). After weaning, CLBP animals showed a better MEP recovery, especially in the L1-L5 region (99 ± 7 vs 70 ± 13%; P < 0.001). The histological analysis did not show significant differences in the necrosis extension in the thoracic spinal cord. A different situation was seen in the L1-L5 area: all animals with isolated SCP, but only 50% of the CLBP animals presented a score of >5. A higher grade of lumbar ischaemia could be seen after isolated SCP (score: 5.9 ± 0.6 vs 3.6 ± 2.9). CONCLUSION: The prolonged SCP provides an insufficient lumbar spinal cord protection during the FET procedure at 28°C. The use of a low-flow LBP in addition to SCP may reduce functional and structural spinal damage.

Plattenepithelkarzinom in Verbindung mit einer roten Tätowierung.

HINTERGRUND UND ZIELE: Obwohl Tätowierungen in den letzten Jahren außerordentlich beliebt geworden sind, wurde in der Literatur bisher nur über wenige Fälle schwerer Reaktionen berichtet, die zu einer malignen Transformation führten. Dies steht im Kontrast zu der praktisch unüberschaubaren Zahl an Tätowierungen weltweit. Die Zusammensetzung der für Tätowierungen verwendeten Farbstoffe variiert stark, und selbst gleiche Farbtöne können unterschiedliche Komponenten enthalten. Das Ziel unserer Studie war es zu untersuchen, auf welche Weise Tätowierungen möglicherweise Hautkrebs auslösen können. PATIENTEN UND METHODEN: Wir berichten über den seltenen Fall einer 24-jährigen Frau, bei der sich sieben Monate nachdem sie eine Tätowierung auf dem Fußrücken erhalten hatte in unmittelbarer Nähe des verwendeten roten Farbstoffs ein Plattenepithelkarzinom entwickelte. Die Komplikationen begannen mit einer unspezifischen Schwellung. Die Läsion wurde histologisch untersucht. Die Zusammensetzung des inkorporierten Farbstoffs wurde mittels Rasterelektronenmikroskopie in Kombination mit energiedispersiver Elementanalyse analysiert. Zur weiteren Charakterisierung wurden Thermogravimetrie und Pulverdiffraktometrie eingesetzt. ERGEBNISSE UND SCHLUSSFOLGERUNGEN: Der Tätowierungsfarbstoff enthielt hauptsächlich Bariumsulfat; Spuren von Al, S, Ti, P, Mg und Cl ließen sich ebenfalls nachweisen. Bei der Analyse zeigten sich Pigmentgranula unterschiedlicher Größe. In seltenen Fällen kann Tätowierungstinte karzinogene Effekte haben, die multifaktoriell zu sein scheinen.

Squamous cell carcinoma in association with a red tattoo.

BACKGROUND AND OBJECTIVES: Although tattoos have become exceedingly popular in recent years, only few cases of severe reactions leading to malignant transformation have been reported in the literature. This stands in contrast to the virtually innumerable number of tattoos worldwide. The composition of tattoo dyes is highly variable, and even the same colors may contain different compounds. The objective of our study was to investigate in what way tattoo dyes may potentially trigger skin cancer. PATIENT AND METHODS: We report the rare case of a 24-year-old woman who - seven months after getting a tattoo on the back of her foot - developed a squamous cell carcinoma in close proximity to the red dye used. Complications started in the form of nonspecific swelling. The lesion was histologically examined. The composition of the incorporated dye was analyzed using scanning electron microscopy in combination with energy dispersive element analysis. Thermogravimetry and powder diffraction were used for further characterization. RESULTS AND CONCLUSIONS: While the tattoo dye primarily consisted of barium sulfate, traces of Al, S, Ti, P, Mg, and Cl were also detected. The analysis showed pigment granules of varying sizes. In rare cases, tattoo inks may have carcinogenic effects, which appear to be multifactorial.

Effect of bisphosphonates on macrophagic THP-1 cell survival in bisphosphonate-related osteonecrosis of the jaw (BRONJ).

OBJECTIVES: Immune deficiency and bacterial infection have been suggested to play a role in the pathophysiology of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Zoledronate was previously found to promote THP-1 cell death. To examine this hypothesis with all commonly prescribed bisphosphonates, we tested the effect of (nitrogen-containing) ibandronate, risedronate, alendronate, pamidronate, and (non-nitrogen-containing) clodronate on macrophagic THP-1 cells. STUDY DESIGN: Activated THP-1 cells were exposed to .5 to 50 µM of nitrogen-containing bisphosphonates and .5 to 500 µM of clodronate. Cell adherence and survival were assessed in vitro using the xCELLigence real-time monitoring system. Results were confirmed histologically and verified with Live/Dead staining. RESULTS: All bisphosphonates inhibited THP-1 cell adherence and survival dose and time dependently, significant for zoledronate, alendronate, pamidronate, and clodronate in high concentrations (50 µM and 500 µM; P < .05). Low concentrations (0.5 µM) of risedronate, alendronate, and pamidronate prolonged the inflexion points of THP-1 cell survival compared with controls (P < .05). THP-1 cells exhibited no cytomorphologic changes at all concentrations. CONCLUSIONS: Commonly prescribed bisphosphonates inhibit the survival of macrophagic THP-1 cells dose-dependently without altering morphology. This may suggest a local immune dysfunction reflective of individual bisphosphonate potency leading to the pathogenesis of BRONJ.

The Influence of Various Parameters on the Success of Sensor-Controlled Scalp Cooling in Preventing Chemotherapy-Induced Alopecia.

BACKGROUND: The influence of systemic comorbidities on the success of scalp cooling during chemotherapy (CT) is widely unexplored. Comorbidities often require additional medication which itself can occasionally cause alopecia. This study investigates the influence of selected parameters on the efficacy of scalp cooling for the prevention of CT-induced alopecia. PATIENTS AND METHODS: 226 cancer patients were treated with various CT regimens in combination with sensor-controlled scalp cooling. 136 breast cancer patients received (neo)adjuvant therapy, and 76 of these patients received epirubicine and cyclophosphamide (4× EC 3w) followed by paclitaxel (12× T w). The following parameters were prospectively investigated: chemotherapy-induced alopecia, systemic comorbidities and co-medication, nicotine abuse, hair treatment, menopausal status, and trichologic status. RESULTS: Scalp cooling was successful (no or not visible hair loss; common toxicity criteria 0-1) in 65% of all patients, in 65% of the 136 breast cancer patients, and in 68% of the 76 patients receiving EC/T. In this subgroup, premenopausal patients (p = 0.009) and those without systemic comorbidities (p = 0.003), without co-medication (p < 0.001) and with high hair density (p = 0.038) showed less hair loss during CT; an effect was also seen for nicotine abuse (p = 0.023). Hair length and hair treatment had no significant influence. CONCLUSION: Sensor-controlled scalp cooling represents an effective addition to supportive cancer therapy. The success of scalp cooling depends on the applied CT regimen. Parameters like menopausal status, systemic comorbidities, medication, nicotine abuse, and original hair density also influence the outcome of hair loss prevention.

Measurement with microscopic MRI and simulation of flow in different aneurysm models.

PURPOSE: The impact and the development of aneurysms depend to a significant degree on the exchange of liquid between the regular vessel and the pathological extension. A better understanding of this process will lead to improved prediction capabilities. The aim of the current study was to investigate fluid-exchange in aneurysm models of different complexities by combining microscopic magnetic resonance measurements with numerical simulations. In order to evaluate the accuracy and applicability of these methods, the fluid-exchange process between the unaltered vessel lumen and the aneurysm phantoms was analyzed quantitatively using high spatial resolution. METHODS: Magnetic resonance flow imaging was used to visualize fluid-exchange in two different models produced with a 3D printer. One model of an aneurysm was based on histological findings. The flow distribution in the different models was measured on a microscopic scale using time of flight magnetic resonance imaging. The whole experiment was simulated using fast graphics processing unit-based numerical simulations. The obtained simulation results were compared qualitatively and quantitatively with the magnetic resonance imaging measurements, taking into account flow and spin-lattice relaxation. RESULTS: The results of both presented methods compared well for the used aneurysm models and the chosen flow distributions. The results from the fluid-exchange analysis showed comparable characteristics concerning measurement and simulation. Similar symmetry behavior was observed. Based on these results, the amount of fluid-exchange was calculated. Depending on the geometry of the models, 7% to 45% of the liquid was exchanged per second. CONCLUSIONS: The result of the numerical simulations coincides well with the experimentally determined velocity field. The rate of fluid-exchange between vessel and aneurysm was well-predicted. Hence, the results obtained by simulation could be validated by the experiment. The observed deviations can be caused by the noise in the measurement and by the limited resolution of the simulation. The resulting differences are small enough to allow reliable predictions of the flow distribution in vessels with stents and for pulsed blood flow.

ZrO2 nanoparticles labeled via a native protein corona: detection by fluorescence microscopy and Raman microspectroscopy in rat lungs.

ZrO2 nanoparticles are frequently used in composite materials such as dental fillers from where they may be released and inhaled upon polishing and grinding. Since the overall distribution of ZrO2 NP inside the lung parenchyma can hardly be observed by routine histology, here a labeling with a fluorphore was used secondary to the adsorption of serum proteins. Particles were then intratracheally instilled into rat lungs. After 3 h fluorescent structures consisted of agglomerates scattered throughout the lung parenchyma, which were mainly concentrated in alveolar macrophages after 3 d. A detection method based on Raman microspectroscopy was established to investigate the chemical composition of those fluorescent structures in detail. Raman measurements were arranged such that no spectral interference with the protein-bound fluorescence label was evident. Applying chemometrical methods, Raman signals of the ZrO2 nanomaterial were co-localized with the fluorescence label, indicating the stability of the nanomaterial-protein-dye complex inside the rat lung. The combination of Raman microspectroscopy and adsorptive fluorescence labeling may, therefore, become a useful tool for studying the localization of protein-coated nanomaterials in cells and tissues.

Spinal cord ischemia after selective cerebral perfusion in a porcine "frozen elephant trunk" simulation model.

BACKGROUND: The "frozen elephant trunk" procedure (FET) represents the therapy of choice for extended aortic diseases. The aim of our study was to analyze whether 90 minutes of selective cerebral perfusion (SCP) at 28 °C followed by permanent occlusion of the thoracic segmental arteries (TSA) would cause spinal cord ischemia in a porcine model. METHODS: 14 pigs (41 ± 3 kg) were cooled on CPB to 28 °C. After aortic clamping, SCP was established for 90 minutes. Randomly, in 7 animals the TSA were clipped (T4-T13); the TSA of 7 animals remained untouched. After the animals were weaned from CPB, hemodynamic data were registered for 120 minutes. Regional spinal cord blood flow (SCBF) was calculated, and motor-evoked potentials (MEP) were assessed at 6 time points. After sacrifice of the animals, the spinal cord was analyzed histologically by use of a schematic grading system (0 = normal; 8 = total necrosis). RESULTS: During SCP the SCBF was maintained at baseline (5.9 ± 2.4 mL/min/100 g) in the T4-T13 region but showed a decrease (from 8.4 ± 4.3 to 1.3 ± 1.5 mL/min/100 g) in the L1-L5 region. During reperfusion it increased, with two to three times higher values in the nonclipped animals. After 90 minutes of SCP, the MEP reached lower levels in the L1-L5 region of the TSA-clipped animals: 59% ± 7% vs 84 ± 15% (vastus medialis muscle) and 48% ± 6% vs 82% ± 26% (tibialis anterior muscle). The MEP recovered only in the nonclipped group. Higher ischemia rates were seen in the L1-L5 region of the TSA-clipped animals (score: 6.0 ± 0.6 vs 2.5 ± 2.3). CONCLUSIONS: 90 minutes of SCP provided sufficient spinal cord protection during arch replacement at 28 °C. In combination with permanent TSA occlusion, the lumbar spinal cord perfusion may be altered, which causes functional and structural damage.

Macrophages and bisphosphonate-related osteonecrosis of the jaw (BRONJ): evidence of local immunosuppression of macrophages in contrast to other infectious jaw diseases.

OBJECTIVES: Bisphosphonates (BIP) are well established in bone diseases. A serious side effect is the bisphosphonate-related osteonecrosis of the jaw (BRONJ). Among different aetiology factors, local suppression of immune functions is gaining interest. The aim of this study was to analyze the function of macrophages in BRONJ in contrast to patients with osteoradionecrosis (ORN) and secondary chronic osteomyelitis (OM) of the jaws. Samples were also taken from patients with bisphosphonate medication (BP) without signs of infection, radiation therapy (RA), and osteoporosis (OP) as controls. MATERIAL AND METHODS: One hundred five patients with surgery to the jaw were included in this study: 33 patients with BRONJ, 17 with ORN, 11 with secondary chronic OM, 8 with RA, 25 with BP medication and 11 with OP. Samples were histologically analysed and monocytes/macrophages stained using CD14 and CD68. The number of positively marked cells was counted per view (pv), and the CD68/CD14 ratio was calculated. Statistically, the Naïve-Bayes and decision-tree classifier were used. RESULTS: The number of CD14 positive cells was 10.3 cells/pv in the BRONJ-group in as compared to 5 in the ORN- and 3.8 in the OM-group respectively. The number of CD68 positive cells was 11.4/pv (BRONJ-group) as compared to 14/pv (ORN-group) and 12.7/pv (OM-group). With 0.89, the BRONJ-group showed a statistically different CD68/CD14 ratio than ORN-group with 3.39 and OM-group with 3.03. CONCLUSIONS: Our results indicate a different expression of CD14 and CD68 markers of monocytes/macrophages in BRONJ as compared to other jaw infections. This could be a sign of macrophage immunosuppression by BPs. In contrast, patients receiving BP medication without BRONJ showed no differences to other controls. CLINICAL RELEVANCE: This is the first study that clinically indicates a compromised macrophage function at BRONJ sites in contrast to ORN or secondary OM sites. The BRONJ itself could be forwarded by this effect.

Material attrition and bone micromorphology after conventional and ultrasonic implant site preparation.

OBJECTIVES: Little is known about the recently introduced ultrasonic implant site preparation. The purpose of this study was to compare material attrition and micromorphological changes after ultrasonic and conventional implant site preparations. MATERIAL AND METHODS: Implant site preparations were performed on fresh bovine ribs using one conventional (Straumann, Freiburg, Germany) and two ultrasonic (Piezosurgery; Mectron Medical Technology, Carasco, Italy and Variosurg; NSK, Tochigi, Japan) systems with sufficient saline irrigation. Sections were examined by environmental scanning electron microscopy (ESEM). Energy-dispersive X-ray spectroscopy (EDX) was performed to evaluate the metal attrition within the bone and the irrigation fluid. RESULTS ESEM: After conventional osteotomy, partially destroyed trabecular structures of the cancellous bone that were loaded with debris were observed, whereas after ultrasonic implant site preparations, the anatomic structures were preserved. EDX: None of the implant site preparation methods resulted in metal deposits in the adjacent bone structures. However, within the irrigation liquid, there was significantly higher metal attrition with ultrasonic osteotomy (P < 0.0001 and P < 0.0001 for Mectron and NSK, respectively). Whereas for Straumann system used, 15.5% of the SEM/EDX findings were drill-origin metals, this percentage increased to 37.3% and 37.9% with the application of Mectron and NSK, respectively. CONCLUSIONS: Ultrasonic implant site preparation is associated with the preservation of bone microarchitecture and with the increased attrition of metal particles. Therefore, copious irrigation seems to be even more essential for ultrasonic implant site preparation than for the conventional method.

Salinomycin induces autophagy in colon and breast cancer cells with concomitant generation of reactive oxygen species.

BACKGROUND: Salinomycin is a polyether ionophore antibiotic that has recently been shown to induce cell death in human cancer cells displaying multiple mechanisms of drug resistance. The underlying mechanisms leading to cell death after salinomycin treatment have not been well characterized. We therefore investigated the role of salinomycin in caspase dependent and independent cell death in colon cancer (SW480, SW620, RKO) and breast cancer cell lines (MCF-7, T47D, MDA-MB-453). METHODOLOGY/PRINCIPAL FINDINGS: We detected features of apoptosis in all cell lines tested, but the executor caspases 3 and 7 were only strongly activated in RKO and MDA-MB-453 cells. MCF-7 and SW620 cells instead presented features of autophagy such as cytoplasmic vacuolization and LC3 processing. Caspase proficient cell lines activated autophagy at lower salinomycin concentrations and before the onset of caspase activation. Salinomycin also led to the formation of reactive oxygen species (ROS) eliciting JNK activation and induction of the transcription factor JUN. Salinomycin mediated cell death could be partially inhibited by the free radical scavenger N-acetyl-cysteine, implicating ROS formation in the mechanism of salinomycin toxicity. CONCLUSIONS: Our data indicate that, in addition to its previously reported induction of caspase dependent apoptosis, the initiation of autophagy is an important and early effect of salinomycin in tumor cells.

Experimental murine model of primary high grade undifferentiated pleomorphic sarcoma not otherwise specified.

BACKGROUND: Undifferentiated pleomorphic sarcoma not otherwise specified (NOS) is a malignant neoplasm of uncertain origin arising both in the soft tissue and the bone. The WHO classified this tumour in 2002 but controversy has plagued this entity due to limited availability of tissue for study. The aim of this study was to establish a reproducible xenograft model of primary human undifferentiated pleomorphic sarcoma NOS. MATERIALS AND METHODS: Primary human sarcoma samples were divided into tumour fragments and transplanted subcutaneously in mice. Sarcoma xenografts were analysed histolomorphologically (light/electron-microscopy; immunohistochemistry). RESULTS: All tumours resulted in viable sarcoma NOS xenografts demonstrating similar histological patterns. In both the original tumours and the xenografts, tumour necrosis was found ranging from 15% to 25%. The background stroma of the xenografts was hyalinised like the primary sarcoma. Electron microscopical analyses showed good maintenance of ultrastructure. CONCLUSION: Implantation of intact tumor fragments yielded in a complete tumor take rate. The development of new cancer therapeutics requires animal models that closely resemble the human patient. This study provides ideal animal models for the research of pathogenesis and pathobiology of primary human undifferentiated pleomorphic sarcoma NOS.

Talcum induced pneumoconiosis following inhalation of adulterated marijuana, a case report.

BACKGROUND: Talcosis, a granulomatous inflammation of the lungs caused by inhalation of talcum dust, is a rare form of pneumoconiosis. Besides inhalative occupational exposure, intravenous abuse of adulterated drugs is a major cause for this condition. Minerals such as talcum (magnesium silicate) and sand (predominant silicon dioxide) are used to increase both volume and weight of illicit substances. In intravenous heroin-abuse, talcosis is a well-known complication. Here we describe a case of talcosis caused by inhalative abuse of adulterated marijuana. CLINICAL HISTORY: A 29-year old man presented with persistent fever, dyspnea and cervical emphysema. He admitted consumption of 'cut' marijuana for several years, preferentially by water pipe smoking. MORPHOLOGIC FINDINGS: Lung-biopsies showed chronic interstitial lung disease, anthracotic pigments and birefringent material. Energy dispersive x-ray spectroscopy revealed silicon-containing particles (1-2 µm) and fine aluminum particles (< 1 µm), magnesium and several other elements forming a spectrum compatible with the stated water pipe smoking of talcum-adulterated marijuana. CONCLUSIONS: The exacerbated chronic interstitial lung disease in a 29-year old patient could be attributed to his prolonged abuse of talcum-adulterated marjuana by histopathology and x-ray spectroscopy. Since cannabis consumption is widely spread among young adults, it seems to be justified to raise attention to this form of interstitial pulmonary disease. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnomx.eu/vs/krause/html/start.html.

A novel xenograft model with intrinsic vascularisation for growing undifferentiated pleomorphic sarcoma NOS in mice.

PURPOSE: Preclinical development of antisarcoma therapy is primarily based on the subcutaneous transplantation of sarcoma xenografts. Tumour cell survival remains a hurdle of current models, which has been attributed to the hypoxic conditions following transplantation. We hypothesised that sarcoma models with an intrinsic tissue-engineered vascular supply are easily reproducible. The aim of this study was to establish a novel vascularised xenograft model. MATERIALS AND METHODS: Primary human soft tissue sarcomas were transplanted into a silicon chamber and placed around the superficial epigastric vessels of nude mice. Sarcoma xenograft samples were assessed histomorphologically. RESULTS: All sarcoma xenografts engrafted, leading to solid tumours. Histological, immunohistochemical staining and light/electron microscopy confirmed the xenografts as identical high-grade pleomorphic sarcomas (NOS) compared with the original patients' tumours. CONCLUSION: This novel sarcoma xenograft model with an intrinsic vascular supply could be of high value for studying human soft tissue sarcomas and their therapy.

The Vascularised Groin Chamber: A Novel Model for Growing Primary Human Liposarcoma in Nude Mice.

BACKGROUND: The preclinical development of anti-sarcoma drugs has been primarily based on the subcutaneous transplantation of xenografts. Transplant survival remains an obstacle of current models which has been attributed to the period of hypoxia after transplantation. We hypothesized that primary soft tissue sarcoma models with an intrinsic tissue engineered vascular supply would be easily reproducible. The aim of this study was to establish a model of primary human soft tissue sarcoma with an intrinsic vascular supply. METHODS: Primary soft tissue sarcoma cells from resected human liposarcomas isolated and divided into tumour fragments were transplanted into a silicon chamber, placed around the superficial epigastric vessels in mice. Sarcoma xenograft samples were analysed histomorphologically (light/electron microscopy and immunohistochemistry). RESULTS: All primary soft tissue sarcoma transplants engrafted, leading to solid tumours within 3 weeks. Histological and immunohistochemical staining confirmed the mouse xenografts as identical high grade liposarcomas compared to original tumour tissue. CONCLUSION: This study established a reproducible xenograft model of primary human liposarcoma. This animal model could be of high value for studying human soft tissue sarcomas and their therapy.