Zone Of Necrosis Research Articles

TMIC-05. GLIOBLASTOMA CONTAINS TOPOLOGICALLY DISTINCT PROLIFERATIVE AND METABOLICALLY DEFINED SUBPOPULATIONS OF NESTIN AND GLUT1-POSITIVE CELLS

Abstract Glioblastoma (GBM), the most aggressive primary brain malignancy, consists of diverse cell subpopulations expressing a variety of cell lineage markers. Improvements in GBM therapy and survival require a deeper knowledge of the shifting subpopulations of tumorigenic cells within typical GBMs and their relative vulnerabilities. GBM development is associated with the appearance of highly proliferative tumor cells that lead to a hypoxic, metabolically reprogrammed, immunosuppressive microenvironment that favors tumor progression. In addition, GBM contains self-renewing, tumorigenic cancer stem cells (CSC) that contribute to tumor initiation and therapeutic resistance. Using a combined multicolor immunofluorescent and Hematoxylin and Eosin (H&E) staining approach with archival formalin-fixed, paraffin embedded tissue from primary, recurrent, and autopsy glioblastoma specimens, we have investigated the complex topology of the GBM microenvironment with particular focus on the association and distribution of several important functional and metabolic markers. High-resolution tissue image analysis permitted precise colocalization and quantification of four biomarkers (Ki-67, GLUT1, Nestin, Hif-1a) of the entire specimen image and at the single cell level. Our results demonstrate discrete subpopulations with specific regional localization with respect to blood vessels and to each other. In particular, highly proliferative Nestin-positive cells are preferentially located near blood vessels. These cells do not express GLUT1 and are Hif-1a positive. In contrast, GLUT1-positive cells are negative for Nestin, demonstrate low proliferation, and are preferentially located at the zones of pseudopalisading necrosis, furthest from blood vessels. In addition, GLUT1-positive cells show reduced Hif-1a expression compared to Nestin-positive cells. Our novel approach provides a means to identify, characterize, and monitor the changing nature of GBM before and after various treatment modalities with the ultimate aim of revealing selective vulnerabilities in order to retard or cure this neoplasm.

Monitoring Liver Stiffness Changes during Controlled Hyperthermia and Microwave Ablation Using Point Shear-Wave Elastography.

HomeRadiology: Imaging CancerVol. 1, No. 2 Previous Research HighlightsFree AccessMonitoring Liver Stiffness Changes during Controlled Hyperthermia and Microwave Ablation Using Point Shear-Wave ElastographyLuke WilkinsLuke WilkinsLuke WilkinsPublished Online:Nov 29 2019https://doi.org/10.1148/rycan.2019194013MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked InEmail Take-Away Points■ Major focus: To investigate the changes in liver stiffness following controlled hyperthermia and microwave ablation in an ex vivo bovine model using point shear-wave elastography.■ Key result: Point shear-wave elastography can provide an elasticity threshold predictive of coagulative necrosis development during microwave ablation in an ex vivo liver model.■ Impact: While there are current limitations, there are opportunities for incorporation of more advanced, real-time imaging techniques to more accurately predict zones of coagulative necrosis in tumor ablation.Noninvasive monitoring of thermal ablation can greatly decrease the risk of complications while ensuring treatment efficacy. While some thermal ablation systems have the capacity to provide real-time temperature feedback, it is typically restricted to the temperature at the device level and does not provide information on tissue temperature within the remainder of the treatment cavity. Crocetti et al explore the use of elastography as a potential method to provide real-time temperature monitoring.There are several US elastographic techniques. In point shear-wave elastography (pSWE), an acoustic radiation force is induced within the tissue. The disturbance created within the tissue moves through the tissue as a shear wave. By monitoring the corresponding tissue displacements created by the shear wave under B-mode imaging, inferences can be made regarding the stiffness of the underlying tissue. This is important for thermal ablation as it is well-known that coagulation (protein denaturation and tissue dehydration) occurs at 60°C. However, the effect of thermal-induced changes in the mechanical properties of the liver tissue has not yet been fully investigated. This article sought to investigate the changes in liver stiffness in controlled hyperthermia and microwave ablation (MWA) in an ex vivo animal model.The authors used five samples of ex vivo bovine liver that were uniformly heated to temperatures ranging from 40 to 100°C. B-mode US imaging and pSWE were then performed simultaneously. In addition, MWA was performed in 11 liver samples at 60 W. Shear wave velocity (SWV) was then measured in the regions of interest (ROIs) at 10–40 mm from the antenna. Histopathologic examination was performed to correlate mean values of SWV to treatment associated changes (within, border, or outside necrotic area). The article reports that a steep transition in liver stiffness was observed at 63.0°C ± 2.4. Through this first phase of experiments, the authors determined that the mean SWV at 60°C was 2.5 m/sec (defined as Avg60). For the next set of experiments, the threshold was defined as Avg60 + 0.5 m/sec or 3 m/sec. Eight of nine experiments showed that following stoppage of ablation when the predetermined ROI reached threshold SWV of 3 m/sec, the ROI was within the necrotic area at histologic examination. While this is notable, there was no correlation between SWV values for outside, border, and within necrosis. This markedly limits current clinical applicability of this technology. Future research may allow more accurate methods for detecting changes in tissue stiffness that would be able to predict tissue still outside the necrotic zone.Highlighted ArticleCrocetti L, Calcagni F, Gherarducci G, et al. Monitoring of thermal-induced changes in liver stiffness during controlled hyperthermia and microwave ablation in an ex vivo bovine model using point shear wave elastography. Cardiovasc Interv Radiol 2019;42(5):744–750. doi: https://doi.org/10.1007/s00270-018-02152-yHighlighted ArticleCrocetti L, Calcagni F, Gherarducci G, et al. Monitoring of thermal-induced changes in liver stiffness during controlled hyperthermia and microwave ablation in an ex vivo bovine model using point shear wave elastography. Cardiovasc Interv Radiol 2019;42(5):744–750. doi: https://doi.org/10.1007/s00270-018-02152-y Crossref, Medline, Google ScholarArticle HistoryPublished online: Nov 29 2019 FiguresReferencesRelatedDetailsCited ByRecommended Articles Elastography in Chronic Liver Disease: Modalities, Techniques, Limitations, and Future DirectionsRadioGraphics2016Volume: 36Issue: 7pp. 1987-2006US Elastography in Hepatic Fibrosis—Radiology In TrainingRadiology2021Volume: 299Issue: 2pp. 264-271Quantitative Elastography Methods in Liver Disease: Current Evidence and Future DirectionsRadiology2018Volume: 286Issue: 3pp. 738-763US Time-Harmonic Elastography: Detection of Liver Fibrosis in Adolescents with Extreme Obesity with Nonalcoholic Fatty Liver DiseaseRadiology2018Volume: 288Issue: 1pp. 99-106Update to the Society of Radiologists in Ultrasound Liver Elastography Consensus StatementRadiology2020Volume: 296Issue: 2pp. 263-274See More RSNA Education Exhibits Ultrasound Elastography Methods: Physical Principles, Techniques, and IndicationsDigital Posters2018Spleen Elastography and Portal Hypertension: An Overview and the Nitty-GrittiesDigital Posters2018Ultrasound Elastography in Children: How We Do it and What is it Helpful For?Digital Posters2019 RSNA Case Collection Hepatic AdenomatosisRSNA Case Collection2021 Cholecystitis and CholedocholithiasisRSNA Case Collection2020Radioembolization of Liver Metastasis RSNA Case Collection2020 Vol. 1, No. 2 Metrics Downloaded 178 times Altmetric Score PDF download

3134 Rare Complication of Delayed Bleeding After Polypectomy

INTRODUCTION: Colonoscopic polypectomies have been the mainstay in polyp removal since the 1970s and are associated with a much better morbidity and mortality than surgery. However, clinically evident bleeding can occur in 0.2-1.0% of cases. Herein lies a case report of postpolypectomy bleeding following a routine esophagogastroduodenoscopy and colonoscopy. We also discuss the risk factors and management of these patients. CASE DESCRIPTION/METHODS: Patient is a 77 year old male who present to the Emergency Department from home after an elective EGD and colonoscopy earlier that day. The patient was found to have a deep antral polyp and required cautery. A sigmoid polyp was also found, and was removed. After the elective procedure earlier in the day, the patient denied any signs overt bleeding. However, upon returning home he felt very weak. The patient had a bloody bowel movement at home and became pale and diaphoretic. Patient was taken to Emergency Department and found to be hypotensive at 60/40 mmHg and had a witnessed episode of hematemesis. Hemoglobin on admission was 8.0 g/dL. Protonix drip was started yet despite a 1L bolus of saline and 2 units of RBCs in ED, patient remained unstable. His AIMS65 score was 3 which was indicative of a 10.3% mortality. Patient was on coumadin for afib but it was held 5 days prior to procedures. Overnight patient had a 3 more bloody bowel movements and 5 more units of RBCs given, however he remained hypotensie and required ICU monitoring and norepinephrine. Emergent EGD revealed no active bleeding but a large 2 cm clean based ulcer where antral polypectomy occurred earlier. No intervention was done due to lack of active bleeding and size of ulcer. By day 9 patient had hemodynamically stabilized and biopsy from initial endoscopy resulted as hyperplastic histology concerning for mild dysplasia. DISCUSSION: Bleeding can occur immediately following a polypectomy or can be delayed from hours to weeks. Delayed PPB can occur due to sloughing of eschar or scab that covered a blood vessel, or an increasing zone of necrosis induced by the thermal energy used to resect the polyp and cauterize the site. Rates of delayed PPB range from 0.02-2.0% with a variety of risk factors. The larger the polyp, the higher the risk of PPB with some reports indicating an increase incidence of 9-13% for every 1 mm in polyp diameter. Patients should have any antiplatelet therapy held, with the exclusion of aspirin, prior to these procedures. NSAIDs should be avoided up to two weeks after polypectomies.

Numerical simulation of cryosurgery in biological tissue with developed circulatory system

This paper is devoted to the modeling of the cryogenic impact on biological tissue with a developed circulatory system: large blood vessels, dense distributed small vessels and capillaries penetrating the tissue. The case of cryogenic destruction of a cancer tumor localized near a large artery is considered. The paper presents a direct numerical simulation of the temperature distribution evolution in biological tissue including the calculation of blood flow parameters in a vessel. The mathematical model is based on the Pennes bioheat transfer model with enthalpy modification and the quasi-one-dimensional hemodynamic model of blood flow in arteries, taking into account local changes in the elastic properties of the vessel walls due to strong cooling of adjacent tissue. A numerical algorithm based on explicit finite-volume approximation of the heat transfer model and the hybrid characteristic scheme (after splitting the equation with respect to physical processes) for numerical solution of hyperbolic systems is developed in order to simulate cryosurgery for the tumor near the artery. The main focus of the paper is a numerical study of the circulatory system parameters’ influence on the shape of the final distribution of the cellular necrosis zone. We study the dependence of the necrosis front penetration depth on the perfusion power which characterizes the density of capillary distribution, the peak and background rates of blood flow in the artery, the diameter of the blood vessel and the thickness of its walls.

Ethylmethylhydroxypyridine succinate, acetylcysteine and choline alphoscerate improve mitochondrial function under condition of cerebral ischemia in rat

The study was devoted to see the effect of ethylmethylhydroxypyridine succinate, acetylcysteine and choline alphoscerate on the mitochondrial function under condition of experimental cerebral ischemia in rat. An integrated approach was used with the assessment of changes in the respirometric and antiapoptotic functions of mitochondria. It was found that the application of the objects under study contributed to a decrease in the intensity of glycolysis and the restoration of aerobic glucose metabolism with an increase in ATP synthesis, as well as a decrease in the dissociation of reactions in mitochondrial complexes I, II, IV and V. In addition, the introduction of the studied drugs reduced the intensity of caspase-dependent and caspase-independent apoptosis reactions, which, together with the restoration of mitochondrial respiratory function, contributed to the decrease in the size of the necrosis zone of the brain.
 Video Clip of Methodology:
 Rat middle cerebral artery occlusion: 8 min 7 sec Full Screen Alternate

Metaphyseal Core Decompression of the Distal Radius for Early Lunate Necrosis.

Background: Metaphyseal core decompression of the distal radius (MCD) is clinically effective in early lunate necrosis without changing individual wrist mechanics. Its concept is based on the induction of physiologic mechanisms known as physiologic fracture healing response. However, this biological concept does not yet have its place in the historically developed mechanical concepts about Kienböck's disease and requires more detailed clarifications to understand when a change of individual wrist mechanics might be unnecessary. Methods: Thirteen consecutive cases, Lichtman stage I (n = 1) or II (n = 12), confirmed by conventional MRI, were treated by MCD. Time off work, changes in magnetic resonance imaging of the lunate, as well as clinical outcome using modified Mayo wrist score were evaluated at final follow-up. Results: Return to work was at six (1-10) weeks after surgery. MRI controls at short-term generally demonstrated stop of progression and signs of bone healing. Independently from ulna variance complete signal normalization was observed in six and a distinct, yet incomplete decrease of lunate bone marrow edema and zones of fat necrosis was confirmed in further six cases after a mean of 21 (13-51) weeks. One patient had radiographic controls only, stating normal healing at 56 months. After a mean follow-up of 37 (12-70) months the clinical outcomes were excellent in eleven and good in two cases (mean 95% in modified Mayo wrist score). Conclusions: In stage I and II lunate necrosis MCD stops disease progression, it improves clinical symptoms and induces normalization of lunate bone signal alterations in MRI. Findings suggest that stage I and II lunate necrosis can be effectively treated without alterations of individual wrist mechanics. Future studies are necessary to readjust common concepts regarding Kienböck's disease, especially focusing on conservative therapy.

Evaluation of the qualitative and quantitative composition of or al microbiota in patients with medial osteonecrosis of the jaw

Aim. To determine the qualitative and quantitative composition of the oral microbiota in patients with medial osteonecrosis of the jaw (MOJ). Materials and methods. Microbiota was evaluated in 15 patients with medial osteonecrosis of the jaw. An assessment was made of 12 groups of optional and obligate-anaerobic microorganisms. Evaluation of the qualitative and quantitative composition of oral microbiota in patients with MOJ was performed by real-time polymerase chain reaction (PCR-RT). Results. The aerobic-anaerobic microbiota composition in patients with MOJ in the oral fluid and separated from the fistula is presented. The values of the total bacterial mass (TBM) and all anaerobic microorganisms in the oral fluid in patients with MOJ before treatment were higher by 1-3 orders of magnitude than in healthy individuals. In the jaw, separated from the fistula in the zone of necrosis of the jaw, these parameters were higher by 2-4 orders than in the oral fluid. Prior to surgery, a course of antibiotic therapy was conducted for 7 days. As a result of the therapy, the parameters of anaerobic microflora in the oral fluid decreased. The use of cefazolin was more effective than lincomycin. In 1 year after surgical treatment, the index of TBM and the indices of anaerobic microorganisms did not differ from those of healthy individuals. Conclusion. Patients with medical osteonecrosis of the jaw have a high level of anaerobic pathogens in the oral microbiota. The course of antibiotic therapy and surgical intervention are effective methods of treatment of MOJ, as they lead to effective sanation, and allow further endoprosthetics.

К вопросу о механизме патогенеза пелиоза печени

Цель исследования - иммуногистохимическая характеристика пелиоза печени. Методика. Образцы опухолей печени (n=4) изучали с использованием гистологического, гистохимического (импрегнация AgNO3) и иммуногистохимического методов. В качестве первичных антител использовали антитела к Collagen III, Collagen IV, α-SMA, Ki67, CD31, CD34, β-catenin, CD10 и pCEA (Novocastra, UK). Вторичные антитела - универсальные (HiDef Detectionтм HRP Polymer system, «Cell Marque», США). Интенсивность иммуногистохимической окраски оценивали в баллах: «1+» - 1-(10% клеток), «2+» - (11-50% клеток), «3+» - (≥51% клеток). Результаты представляли в процентах от общего числа иммунопозитивных клеток. Результаты. Гистологическое исследование показало, что стенка кисты представлена склерозированной волокнистой тканью с выраженной мононуклеарной инфильтрацией. В перипортальных трактах отчетливо выражены скопления гемосидерина и обширные зоны ступенчатого некроза. В прилежащей печеночной паренхиме определялись мультифокальные, синусоидальные эктазии с кровяным и/или плазменным содержимым, охватывающие все 3 зоны печеночной дольки. При гистохимическом исследовании в этих образованиях выявлялись ретикулярные волокна без признаков деструкции. При иммунногистохимическом исследовании вдоль синусоидов и выстилки полостей было обнаружено увеличение экспрессии Collagen III, Collagen IV (96.6±0.2% и 97.2±0.3% соответственно) и α-SMA (94%±0,5). Степень экспрессии на CD31 (87.3±0.6%) и CD34 (86.3±0.2%) в эндотелии уменьшалась в направлении от триад к центральной вене. Индекс экспрессии Ki-67 был увеличен в макрофагах (28.3±0.2%) и лимфоцитах (12.3±0.7%) синусоидов. Иммунонегативные реакции на β-catenin, CD10 и pCEA исключали опухолевый рост при пелиозе печени. Заключение. Активный синтез белков экстрацеллюлярного матрикса и пролиферация иммунокомпетентных клеток являются ключевыми процессами в патогенезе пелиоза печени на фоне разрушения эндотелиальных коммуникаций. Использованные методы могут быть полезны в дифференциальной диагностике пелиоза и опухолевых процессов в печени. Aim. Characterization of peliosis hepatis using immunohistochemical methods. Methods. The study was performed on archive autopsy samples from patients (n=4) with peliosis hepatis using histological, histochemical (AgNO3 impregnation), and immunohistochemical methods. Murine monoclonal antibodies, anticollagen type III, anticollagen type IV, anti-α-smooth muscle actin, anti-CD31, anti-CD34, and anti-Ki-67 (Novocastra, UK), were used as primary antibodies, and all-purpose antibodies (HiDef Detection ™ HRP Polymer system, Cell Marque:, USA) were used as secondary antibodies. Intensity of immunohistochemical staining was expressed as scores: 1+ = 1-10% of cells, 2+ = 11-50% of cells, and 3+ = ≥51% of cells. Results. The cyst wall consisted of sclerotic fibrous tissue with pronounced mononuclear infiltration, accumulation of hemosiderin in periportal tracts, and zones of piecemeal necrosis. Multifocal, sinusoidal ectasias filled with blood and/or plasma components encompassing all three zones of the hepatic lobe were observed in the adjacent hepatic parenchyma. Histochemical study revealed reticular fibers without signs of destruction in these formations. Immunohistochemical analysis found increased expression of collagen III (96.6±0.2%), collagen IV (97.2±0.3%), and α-SMA (94%±0.5) along sinusoids and cavity lining. The endothelial expression of CD31 (87.3±0.6%) and CD34 (86.3±0.2%) decreased on going from the hepatic triad to the central vein. The expression index, Ki-67, was increased in sinusoid macrophages (28.3±0.2%) and lymphocytes (12.3±0.7%). Reactions to β-catenin, CD10 and pCEA were immune-negative, which excluded tumor growth. Conclusion. The study suggested that the active synthesis of extracellular matrix proteins and the immune cell proliferation are key processes in the pathogenesis of peliosis hepatis during destruction of endothelial communications in hepatic lobes.

Systemic and cardiac susceptibility of immune compromised mice to doxorubicin

BackgroundAnthracycline chemotherapy is an effective and widely used treatment for solid tumors and hematological malignancies regardless of its known cardiotoxicity. The mechanisms of the cardiotoxicity are not fully understood and methods to protect the heart during or following anthracycline chemotherapy are currently unclear. In order to examine the efficacy of human cell based therapy in anthracycline-induced injury, we characterized a mouse model using an immune compromised strain of mice capable of accepting human cells.MethodsImmune compromised mice (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) were repeatedly exposed to pharmaceutical grade doxorubicin (0.5 mg/kg – 4 mg/kg). Cardiotoxicity was assessed by echocardiography and μCT imaging of the coronary vascular bed as well as by flow cytometry and by histological assessments of anthracycline-induced cardiac tissue damage.ResultsThe immune compromised mice were highly susceptible to doxorubicin treatment. Doxorubicin induced both systemic and cardiac toxicities. Gastrointestinal and hepatic injury occurred at 4 mg/kg and 1.5 mg/kg dosing while mice receiving 0.5 mg/kg weekly only displayed hepatic damage. Repeated exposure to 0.5 mg/kg anthracyclines resulted in cardiac toxicity. Flow cytometric analysis of hearts indicated a loss in endothelial and cardiac progenitor cells after doxorubicin treatment. This endothelial loss is corroborated by the lack of small vessels detected by μCT in the hearts of mice exposed to doxorubicin. Histological assessment shows no overt cardiomyocyte injury but livers from mice treated with doxorubicin show marked hepatic plate atrophy with intracytoplasmic and canalicular cholestasis, rare pericentral hepatocellular necrosis and significant zone 3 iron accumulation, likely an indication of metabolic injury due to doxorubicin toxicity.ConclusionsImmune compromised mice are sensitive to doxorubicin therapy resulting in systemic complications in addition to cardiovascular toxicity. Anthracycline-induced cardiotoxicity is observed at very low doses in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice.

Oral administration of ammonium metavanadate and potassium dichromate distorts the inflammatory reaction induced by turpentine oil injection in male rats

Heavy metal pollution is rapidly increasing in the environment. It has been shown that exposure to vanadium and chromium is able to alter the immune response. Nevertheless, the mechanisms by which these metal pollutants mediate their immunomodulatory effects are not completely understood. Herein, we examined the effect of ammonium metavanadate and potassium dichromate on the development of an inflammatory response caused by subcutaneous injection of turpentine oil. We demonstrated that pretreatment of rats with ammonium metavanadate and potassium dichromate for two weeks prior to initiation of the inflammatory response resulted in a wider zone of necrosis surrounding the site of inflammation. The acute inflammatory process in the combined model was characterized by elevated serum levels of IL-10 and decreased serum levels of IL-6 as compared to rats not treated with ammonium metavanadate and potassium dichromate. Ammonium metavanadate and potassium dichromate administration induced a decrease in the proportion of splenic His48HighCD11b/c+ myeloid cells accompanied by a reduced infiltration of the wound with neutrophils. Further analysis showed decreased proportions of CD3+CD4+IFNγ+ and CD3+CD4+IL-4+ T cells in the rats with combined model as compared to inflamed rats not treated with ammonium metavanadate and potassium dichromate. The data suggest that consumption of vanadium and chromium compounds disrupts the inflammatory response through an altered balance of pro- and anti-inflammatory cytokines and inhibition of effector T cell activation and neutrophil expansion.

Osteonecrosis of the femoral head: pathophysiology and current concepts of treatment.

Osteonecrosis of the femoral head is a disabling pathology affecting a young population (average age at treatment, 33 to 38 years) and is the most important cause of total hip arthroplasty in this population. It reflects the endpoint of various disease processes that result in a decrease of the femoral head blood flow.The physiopathology reflects an alteration of the vascularization of the fine blood vessels irrigating the anterior and superior part of the femoral head. This zone of necrosis is the source of the loss of joint congruence that leads to premature wear of the hip.Several different types of medication have been developed to reverse the process of ischemia and/or restore the vascularization of the femoral head. There is no consensus yet on a particular treatment.The surgical treatments aim to preserve the joint as far as the diagnosis could be made before the appearance of a zone of necrosis and the loss of joint congruence. They consist of bone marrow decompressions, osteotomies around the hip, vascular or non-vascular grafts.Future therapies include the use of biologically active molecules as well as implants impregnated with biologically active tissue.Cite this article: EFORT Open Rev 2019;4:85-97. DOI: 10.1302/2058-5241.4.180036

Abstract No. 617 Nonthermal ablation of pancreatic cancer in a pig model, using vascular-targeted photodynamic therapy (VTP)

To examine whether pancreatic cancer in a pig model can be safely ablated using vascular-targeted photodynamic therapy (VTP), a nonthermal ablation modality that combines an intravascular photosensitizer (WST11) and percutaneous laser fibers. Pancreatic tumors (n=8) were induced in 5 Oncopigs (transgenic swine with Cre-inducible p53 and Kras mutations) using an adenoviral vector carrying the Cre recombinase gene. Non-thermal ablation of the tumors was performed using VTP: Intravenous infusion of WST11 (4 mg/kg, 10 min) was followed by near-infrared illumination (753 nm, 20 min) of the tumor through three optical fibers with 1-cm spacing, placed percutaneously into the tumor under CT guidance. Contrast-enhanced CT was performed immediately after, and at 7-days post ablation. Ablation sizes on CT were compared using a t test. Necropsy was performed 7 days post-ablation and lesions were examined histologically. There were no complications after ablation of pancreatic tumors (4 pancreatic head tumors, and 4 pancreatic tail tumors), based on imaging, laboratory results, and clinical evaluation. The average diameters of the ablation zones on contrast-enhanced CT increased from 1.2±0.1 cm at 200 mW/cm to 2.1±0.2 cm at 300 mW/cm (p<0.01). Pathology showed a zone of coagulative necrosis, hemorrhage, and occluded blood vessels. All vessels outside the ablation zone remained patent. VTP can be safely applied for reproducıble ablation of pancreatic tumors, while sparing large blood vessels outside the ablation zone. Preservation of nearby blood vessels could potentially enable ablation of unresectable pancreatic cancer with vascular involvement.

Histologic findings associated with laser interstitial thermotherapy for glioblastoma multiforme

BackgroundLaser-interstitial thermal therapy (LITT) has been supported by some authors as an ablative treatment of glioblastoma multiforme (GBM). Although the effects of LITT have been modeled in vivo, the histologic effects in a clinical circumstance have not been described. We analyzed tissue from a patient who underwent LITT as primary treatment for GBM.Case presentationA 62-year-old male was diagnosed with a left temporal GBM and underwent LITT at an outside institution. Despite corticosteroid therapy, the patient was referred with increasing headache and acalculia associated with progressive peritumoral edema two weeks after LITT procedure. En bloc resection of the enhancing lesion and adjacent temporal lobe was performed with steroid-independent symptom resolution (follow-up, > 2 years). Histologic analysis revealed three distinct histologic zones concentrically radiating from the center of the treatment site. An acellular central region of necrosis (Zone 1) was surrounded by a rim of granulation tissue with macrophages (CD68) (Zone 2; mean thickness, 1.3 ± 0.3 mm [±S.D.]). Viable tumor cells (identified by Ki-67, p53 and Olig2 immunohistochemistry) were found (Zone 3) immediately adjacent to granulation tissue. The histologic volume of thermal tissue ablation/granulation was consistent with preoperative (pre-resection) magnetic resonance (MR)-imaging.ConclusionThese findings are the first in vivo in humans to reveal that LITT causes a defined pattern of tissue necrosis, concentric destruction of tumor and tissue with viable tumor cells just beyond the zones of central necrosis and granulation. Furthermore, MR-imaging appears to be an accurate surrogate of tissue/tumor ablation in the early period (2 weeks) post-LITT treatment. Surgery is an effective strategy for patients with post-LITT swelling which does not respond to steroids.

Comparison of different 4D CT-Perfusion algorithms to visualize lesions after microwave ablation in an in vivo porcine model

Background: Accurate lesion visualization after microwave ablation (MWA) remains a challenge. Computed tomography perfusion (CTP) has been proposed to improve visualization, but it was shown that different perfusion-models delivered different results on the same data set.Purpose: Comparison of different perfusion algorithms and identification of the algorithm enables for the best imaging of lesion after hepatic MWA.Materials and methods: 10 MWA with consecutive CTP were performed in healthy pigs. Parameter-maps were generated using a single-input-dual-compartment-model with Patlak’s algorithm (PM), a dual-input-maximum-slope-model (DIMS), a dual-input-one-compartment-model (DIOC), a single-(SIDC) and dual-input-deconvolution-model (DIDC). Parameter-maps for hepatic arterial (AF) and portal venous blood flow (PF), mean transit time, hepatic blood volume (HBV) and capillary permeability were compared regarding the values of the normal liver tissue (NLT), lesion, contrast- and signal-to-noise ratios (SNR, CNR) and inter- and intrarater-reliability using the intraclass correlation coefficient, Bland-Altman plots and linear regression.Results: Perfusion values differed between algorithms with especially large fluctuations for the DIOC. A reliable differentiation of lesion margin appears feasible with parameter-maps of PF and HBV for most algorithms, except for the DIOC due to large fluctuations in PF. All algorithms allowed for a demarcation of the central necrotic zone based on hepatic AF and HBV. The DIDC showed the highest CNR and the best inter- and intrarater reliability.Conclusion: The DIDC appears to be the most feasible model to visualize margins and necrosis zones after microwave ablation, but due to high computational demand, a single input deconvolution algorithm might be preferable in clinical practice.

The Spectrum of Morphologic Alterations Associated With Infarction in Endometrial Polyps: A Report of 41 Cases.

The authors describe the clinicopathologic features of a group of endometrial polyps that exhibited large areas of infarction, to highlight the spectrum of morphologic alterations that may occur in this setting, including moderate cytologic atypia in a subset. Forty-one infarcted endometrial polyps, classified as such based on the presence therein of confluent zones of stromal necrosis and/or sharply demarcated zones of paucicellular to acellular stromal hyalinization, were assembled from multiple institutions. All were diagnosed in biopsies, polypectomies, or curettages. The morphologic profile of the epithelium associated with the infarcted zones was compared with those of a control group of 40 consecutive noninfarcted polyps. The patients with infarcted polyps ranged in age from 23 to 94 yr and were significantly older than the control group patients (mean ages, 60.8 vs. 49 yr respectively; P=0.02). The most common architectural alteration in infarcted polyps was a distinctive cellular tufting or pseudopapillary change, possibly representing an exuberant iteration of papillary syncytial change, which was seen in 39% of cases. Among the features that were significantly more prevalent in infarcted polyps than the control group were grade 2 pleomorphism (i.e., a 2-3-fold variation in nuclear size and/or shape) (37% vs. 2.5%, respectively; P=0.00029), cellular syncytia (44% vs. 15%; P=0.069), vesicular chromatin greater than background glands (56% vs. 7.5%; P <0.0001), hobnail cells (27% vs. 0%; P=0.0004), clear cells (12% vs. 0%; P=0.055), and eosinophilic cells (56% vs. 15%; P=0.000115). The 2 groups were not significantly different regarding mitotic index and a variety of other morphologic variables. Irrespective of morphology, epithelia within the infarcted zones at least focally showed a core immunophenotype (p53-wild type, p16-diffusely positive; low proliferative index) that was essentially identical to the phenotype displayed by foci of papillary syncytial metaplasia unassociated with polyps in a 10-case comparison group. None of the 34 patients with follow-up information has subsequently been diagnosed with a uterine neoplasm. In summary, infarcted endometrial polyps frequently display a spectrum of cytoarchitecturally atypical epithelial changes. These pseudoneoplastic alterations are most likely degenerative and/or metaplastic in nature.

Determinants of Levels of Cardiac Troponin I in Post-Mortem Blood Sample in Sudden Cardiac Death-An Autopsy Based Study

Cardiac Troponin I (cTnI) is a very sensitive biochemical marker for the diagnosis of myocardial infarction (MI) in Sudden Cardiac Death (SCD). cTnI has nearly absolute myocardial tissue specificity, thereby reflecting even microscopic zones of myocardial necrosis. The aim of this study is to find out the gross and microscopic changes in heart and determinants of elevated levels of cTnI in cases of SCD. This cross sectional study was conducted in 50 cases of SCD brought for medicolegal autopsy at Government Medical College, Thiruvananthapuram. Heart was examined for gross and microscopic changes and blood level of cTnI. The mean value of cTnI was 3.4 (sd – 7.8) ng/dl. Age (>50 years), male sex, BMI (>25), previous history of CAD, family history, diabetes mellitus and hypertension were the determinants of level of cTnI in the postmortem blood. Common morphological findings observed in heart were haemorrhage, hypereosinophilia and oedema. From this study it can be concluded that cTnI assay can be used as a valuable supportive measure for postmortem diagnosis of SCD.

Antihypoxic and anti-ischemic properties of the North Caucasus flora plant extract

Nowdays it is established that ischemic brain damage like ischemic stroke is one of the leading cause of death and disability in the population that assumes relevance development of anti-ischemic drugs. The work studied the anti-hypoxic and anti-ischemic effect of 7 plant extracts. Antihypoxic activity was assessed on models of hypobaric, hypercapnic, histotoxic, hematotoxic hypoxia. Anti-ischemic activity of test-extracts was studied on the focal cerebral ischemia model. Administration of Tagetes patula, Gaillardia pulchella, Sorbaria sorbifolia, Grossularia reclinata, Ribes nigrum, Rubus caesius and Lysimachia punctata extracts contributed to the necrosis zone reduction by 56.6% (p<0.05); 37.3% (p<0.05); 73.2% (p<0.05); 49.4% (p<0.05); 42.5% (p<0.05); 85.5% (p<0.05); 44.2% (p<0.05) and also restored aerobic metabolism in brain tissue. Test - objects increased of the animal lifespan under hypoxia conditions. Based on the data obtained, it is assumed that further studies of North Caucasus flora plant extracts as cerebro-protective agents are promising.

Pathological anatomy of reparative processes in the resected kidney treated with α-tocopherol acetate in experiment

Violation of the integrity of the kidney parenchyma during organ-preserving surgery is always accompanied by functional impairment in that part of the organ. This is due to mechanical damage to the nephron and the development of aseptic necrosis in the area of the resection, followed by development of an ischemic zone that expands during the repair process due to disrupted parenchymal cell metabolism and pressure from regenerating connective tissue.&#x0D; Objective. To investigate the effect of α-tocopherol acetate on repair processes in the kidney parenchyma after an organ-preserving operation in a rat model.&#x0D; Materials and methods. An experimental study was performed on 60 white laboratory rats that underwent resection of the lower pole of the left kidney. Postoperatively, a study group (n = 30) underwent intramuscular injections of a 10% α-tocopherol acetate oil solution, 0.2 ml 2 times a day for 5 days. A control group (n = 30) were left untreated.&#x0D; Results. Compared with the control group, animals in the study group had a narrower zone of total necrosis and less pronounced inflammation and vascular stasis on days 7, 14, and 28 after the operation.&#x0D; Conclusion. Use of the natural antioxidant α-tocopherol acetate in the postoperative period of organ-preserving kidney surgery may accelerate reparative processes in the damaged parenchyma.

Possibilities of use of arc-type discharge low-temperature air plasma of atmospheric pressure for burn wound treatment

Results of experimental assessment of efficiency of use of low-temperature air plasma of the arc category of atmospheric pressure at treatment of burns of skin of the III degree in small laboratory animals are given. It is established that use of low-temperature air plasma of the arc-type discharge of atmospheric pressure allows to accelerate terms of final healing of wounds for 49% (p0,05), to reduce development frequency in them purulent inflammation by 45,5% (p0,01). Positive influence of air and plasma processing on dynamics of the area of a hem which after single influence by 35 days is reduced for 67% is revealed (p0,01). The analysis of a histologic picture confirms acceleration of formation of an extracellular matrix and epitelization against the background of impact of an air and plasma stream on wounds. Processing of a wound of low-temperature air plasma of the arc category of atmospheric pressure after an early surgical escharotomy allows to form on a wound surface a so-called nanofilm of a layer the coagulated proteins of wound exudate and cellular fragments which has selective vapor permeability, reduces an rate of wounds pathogenic infection, prevents drying and as a result, allows to reduce the frequency of development of purulent complications and extent of zones of a secondary necrosis. Influence of a stream of low-temperature air plasma of the arc-type discharge of atmospheric pressure allows to optimize significantly processes of reparative regeneration in a zone of a deep burn of skin at a stage of preparation for their surgical treatment.

Performance of noninvasive laser Doppler flowmetry and laser speckle contrast imaging methods in diagnosis of Buerger disease

Buerger disease (BD) is a nonatherosclerotic, inflammatory, segmental vascular occlusive disease, which affects small and medium-sized arteries and veins and is triggered by substantial tobacco exposure. Angiographic findings consistent with BD are required for diagnosis. Laser Doppler flowmetry (LDF) and laser speckle contrast imaging (LSCI) could represent potential noninvasive alternative techniques to angiography. We report the case of a 49-year-old smoker who developed an ischemic ulcer in the distal segment of the second finger of the left hand. He had no medical history. In our vascular center, LDF and LSCI are conducted routinely for digital artery disease diagnosis. LDF was indicative of digital obstructive artery disease (DOAD). Postocclusive reactive hyperemia, assessed by LCSI, demonstrated no skin blood flow (SBF) perfusion in the distal phalanx of the thumb, index, middle, and auricular fingers. Angiography confirmed BD, showing distally located multisegmental vessel occlusion and corkscrew collaterals in this patient's hands. Ilomedine treatment was initiated and smoking cessation was definitive. Recently, the patient had an improvement in clinical condition despite the persistence of a small zone of necrosis of the left index finger 28 days post-treatment. Our observation suggests that where suspicion of BD is based on clinical criteria, combining LDF and LSCI could represent a noninvasive, safe means of reaching BD diagnosis. Further clinical trials are necessary to confirm this novel observation.