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Investigation of glucocorticoid and dissociated glucocorticoid activity in hepatoma cell lines with specific reference to regulation of the corticosteroid binding globulin (CBG) proximal promoter'Allie-Reid, Fatima 12 1900 (has links)
Thesis (PhD)--Stellenbosch University, 2003. / ENGLISH ABSTRACT: This study investigated the effect of several hormones on the rat corticosteroid binding
globulin proximal promotor and for the first time showed that modulation occurs at the
promotor level and can be correlated with changes in corticosteroid binding globulin
mRNA and protein levels. The effect of various physical and psychological stressors on
rat liver corticosteroid binding globulin mRNA levels was also tested and it was shown
that voluntary running had no effect on rat corticosteroid binding globulin levels but
that involuntary swimming and immobilization decreased rat corticosteroid binding
globulin mRNA levels. Glucocorticoid responsiveness of the corticosteroid binding
globulin promoter was investigated further by using truncated contructs of the
corticosteroid binding globulin proximal promoter. Glucocorticoid responsiveness was
delineated to between -296 and -145bp from the transcription start site an area that
contains putative binding sites for D-site binding protein, hepatic nuclear factor-3 and
CAAT/enhancer binding protein suggesting that these transcription factors may be
involved in glucocorticoid responsiveness of the corticosteroid binding globulin
proximal promoter.
The dissociative glucocorticoid activity of medroxyprogesterone acetate and Compound
A, both putative dissociated glucocorticoids, was compared to standard glucocorticoids
by examining transactivation of glucocorticoid response element-containing reporter
constructs and transrepression of corticosteroid binding globulin gene expression in
hepatic cell lines. Results showed that medroxyprogesterone acetate, but not Compound
A, trans activates only in the presence, but not in the absence, of co-transfected
glucocorticoid receptor. Medroxyprogesterone acetate down modulated dexamethasone
transactivation while the modulatory effect of Compound A depends on the order of addition of Compound A. If added together Compound A has no effect on
dexamethasone transactivation, however, if Compound A was added before
dexamethasone, Compound A significantly decreased dexamethasone transactivation.
Both medroxyprogesterone acetate and Compound A, like glucocorticoids,
transrepressed the rat corticosteroid binding globulin proximal promoter. The potency
of repression was similar but Compound A repressed with a higher efficacy than
medroxyprogesterone acetate. We conclude that Compound A is a completely
dissociated glucocorticoid in contrast to medroxyprogesterone acetate that displays only
partial dissociation, which is dependent on glucocorticoid receptor levels. / AFRIKAANSE OPSOMMING: Tydens hierdie ondersoek is die effek van verskeie hormone op die rot kortikosteroied
bindings globulien proksimale promoter ondersoek en vir die eerste keer is getoon dat
modulering plaasvind op promoter-vlak en dat repressie korrileer met die verandering in
kortikosteroied bindings globulien mRNA-en proteinvlakke. Die effek van verskeie
fisiese en fisiologiese stressors op rotlewer kortikosteroied bindings globulien-mRNAvlakke
is ook getoets en daar is getoon dat willekeurige hardloop geen effek op rot
kortikosteroied bindings globulien-mRNA-vlakke het nie maar dat gedwonge swem en
immobilisering rot kortikosteroied bindings globulien-mRNA-vlakke verlaag.
Glukokortikoied responsiewiteit van die kortikosteroied bindings globulien proksimale
promoter is verder ondersoek deur verkorte konstrukte van die kortikosteroied bindings
globulien te toets. Glukokotikoied responsiewiteit is afgebaken tot tussen -296 en -
145bp vanaf die transkripsie beginplek 'n area wat beweerde bindings setels vir D-setel
bindings protein, hepatosiet faktoor-3 en CCAAT-bindings protein-2 bevat en dus
suggereer dat hierdie transkripsie faktore betrokke mag wees met glukokortikoied
effekte op die kortikosteroied bindings globulien-proksimale promoter.
Die dissosiatiewe glukokortikoied aktiwiteit van medroksiprogesteroon asetaat en
Verbinding A, beide beweerde dissosiatiewe glukokortikoiede, relatief tot standaard
glukokortikoiede is vergelyk deur transaktivering van glukokortikoied reseptor
e1elment-bevattende konstrukte en onderdrukking van kortikosteroied bindings
globulien geen ekspressie in lewersellyne te bestudeer. Medroksiprogesteroon asetaat,
maar nie Verbinding A nie, transaktiveer slegs in die teenwoordigheid, maar nie in die
afwesigheid, van ko-getransfekteerde glukokortikoied reseptore. Medroksiprogesteroon
asetaat moduleer deksametasoon transaktivering afwaarts terwyl die modulerende effek van Verbinding A afhanklik van die orde van Verbinding A byvoeging is. Indien saam
bygevoeg het Verbinding A geen effek op deksametasoon transaktivering nie, maar
indien Verbinding A voor deksametasoon bygevoeg word verlaag Verbinding A
deksametasoon transaktivering. Beide medroksiprogesteroon asetaat and Verbinding A,
soos glukokortikoiede, onderdruk die rot kortikosteroied bindings globulien-proksimale
promoter. Die sterkte van onderdrukking is dieselfde maar Verbinding A onderdruk met
'n hoër effektiwiteit as medroksiprogesteroon asetaat. Ons toon dat Verbinding A 'n
totale dissosiatiewe glukokortikoied is in teenstelling met medroksiprogesteroon asetaat,
wat slegs gedeeltelik dissosiatief is afhangende van glukokortikoied reseptor-vlakke.
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The haematological findings in cryptogenetic splenomegaly with and without cirrhosis and in primary carcinoma of the liverTodd, David, 達安輝 January 1958 (has links)
published_or_final_version / Medicine / Master / Doctor of Medicine
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Pathology of hepatitis B-associated chronic liver disease and hepatocellular carcinoma in Hong KongWu, Pui-chee., 胡沛之. January 1984 (has links)
published_or_final_version / Medicine / Master / Doctor of Medicine
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The future of radiofrequency ablation is looking BETA : short and long term studies of bimodal electric tissue ablation (BETA) in a porcine model.Dobbins, Christopher January 2008 (has links)
Introduction: Radiofrequency ablation (RFA) is a popular method of treating unresectable liver tumours by the use of a high frequency, alternating electrical current that heats and destroys tumour cells. The size of the ablation is limited by localised charring of adjacent tissue that prevents further conduction of the radiofrequency current. In the clinical setting, this results in increased rates of local recurrence in tumours that are greater than 3 cm in diameter as multiple, overlapping ablations need to be performed to treat the one tumour. To overcome this problem, a modified form of RFA called Bimodal Electric Tissue Ablation (BETA) has been created. BETA adds a direct electrical current to the alternating radiofrequency current, thus establishing its bimodal character. When direct currents are used in biological tissues, water is transferred from anode to cathode by a process called electro-osmosis. By attaching the cathode to the radiofrequency electrode, water is attracted to the area thus preventing tissue desiccation and charring. The BETA circuit has been constructed and tested using a porcine model. The aims of the studies are to confirm that larger ablations can be produced with the BETA system and that it is safe to use in an animal model. Three studies have been performed to test these aims in porcine liver. Methods: The first study was designed to compare sizes of the ablation produced between standard RFA and the BETA circuit. This was followed by a long-term study to assess associated changes to liver function and pathological changes within the liver as well as identifying any other treatment related morbidity. The third study assessed the difference in ablation size and safety aspects when the positive electrode of the direct current circuitry was moved from small surface area under the skin to a large surface area on the skin. Results: Ablations with significantly larger diameters are created with the BETA circuit using a multi-tine needle (49.55 mm versus 27.78 mm, p<0.001). This finding was confirmed in the third experiment using a straight needle (25 mm versus 15.33 mm, p<0.001). Ablations produced by the BETA circuit induce coagulative necrosis within the treated liver and the injury heals by fibrosis in a manner similar to other thermal therapies. Significant rises in some serum liver enzymes are seen within 24 hours of treatment but these return to normal within 4 days. An electrolytic type injury can be produced at the site of the positive electrode. By increasing the surface area of this electrode, the risk of tissue damage is decreased but ablations are significantly smaller (18 mm versus 25 mm, p<0.001). Conclusions: The BETA circuit consistently produces significantly larger ablations than RFA. The treatment appears safe but positioning of the positive electrode of the direct current requires careful consideration. Injuries produced behave like other thermal therapies with coagulative necrosis followed by fibrotic healing. As larger ablations are consistently produced, it is hypothesised that with further refinements, tumours greater than 3 cm in diameter could be treated with lower rates of recurrence. / Thesis (M.S.) -- University of Adelaide, School of Medicine, 2008
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Temperature modulated aflatoxin B1 hepatic disposition, and formation and persistence of DNA adducts in rainbow troutZhang, Quan, 1957- 07 May 1992 (has links)
Graduation date: 1992
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The future of radiofrequency ablation is looking BETA : short and long term studies of bimodal electric tissue ablation (BETA) in a porcine model.Dobbins, Christopher January 2008 (has links)
Introduction: Radiofrequency ablation (RFA) is a popular method of treating unresectable liver tumours by the use of a high frequency, alternating electrical current that heats and destroys tumour cells. The size of the ablation is limited by localised charring of adjacent tissue that prevents further conduction of the radiofrequency current. In the clinical setting, this results in increased rates of local recurrence in tumours that are greater than 3 cm in diameter as multiple, overlapping ablations need to be performed to treat the one tumour. To overcome this problem, a modified form of RFA called Bimodal Electric Tissue Ablation (BETA) has been created. BETA adds a direct electrical current to the alternating radiofrequency current, thus establishing its bimodal character. When direct currents are used in biological tissues, water is transferred from anode to cathode by a process called electro-osmosis. By attaching the cathode to the radiofrequency electrode, water is attracted to the area thus preventing tissue desiccation and charring. The BETA circuit has been constructed and tested using a porcine model. The aims of the studies are to confirm that larger ablations can be produced with the BETA system and that it is safe to use in an animal model. Three studies have been performed to test these aims in porcine liver. Methods: The first study was designed to compare sizes of the ablation produced between standard RFA and the BETA circuit. This was followed by a long-term study to assess associated changes to liver function and pathological changes within the liver as well as identifying any other treatment related morbidity. The third study assessed the difference in ablation size and safety aspects when the positive electrode of the direct current circuitry was moved from small surface area under the skin to a large surface area on the skin. Results: Ablations with significantly larger diameters are created with the BETA circuit using a multi-tine needle (49.55 mm versus 27.78 mm, p<0.001). This finding was confirmed in the third experiment using a straight needle (25 mm versus 15.33 mm, p<0.001). Ablations produced by the BETA circuit induce coagulative necrosis within the treated liver and the injury heals by fibrosis in a manner similar to other thermal therapies. Significant rises in some serum liver enzymes are seen within 24 hours of treatment but these return to normal within 4 days. An electrolytic type injury can be produced at the site of the positive electrode. By increasing the surface area of this electrode, the risk of tissue damage is decreased but ablations are significantly smaller (18 mm versus 25 mm, p<0.001). Conclusions: The BETA circuit consistently produces significantly larger ablations than RFA. The treatment appears safe but positioning of the positive electrode of the direct current requires careful consideration. Injuries produced behave like other thermal therapies with coagulative necrosis followed by fibrotic healing. As larger ablations are consistently produced, it is hypothesised that with further refinements, tumours greater than 3 cm in diameter could be treated with lower rates of recurrence. / Thesis (M.S.) -- University of Adelaide, School of Medicine, 2008
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TUMORES HEPÁTICOS MALIGNOS PRIMÁRIOS DE CÃES DA REGIÃO CENTRAL DO RIO GRANDE DO SUL (1965-2012) / PRIMARY CANINE MALIGNANT HEPATIC TUMORS IN RIO GRANDE DO SUL, BRAZIL (1965-2012)Flores, Mariana Martins 25 February 2013 (has links)
Conselho Nacional de Desenvolvimento Científico e Tecnológico / Primary hepatic malignant tumors (PHMT) represent an important cause of death of
dogs at the Laboratório de Patologia Veterinária of the Universidade Federal de Santa Maria
(LPV-UFSM). Based in this information, the prevalence and epidemiological and
immunohistochemical aspects of PHMT were reviewed in dogs necropsied in a 48-year
period (1965-2012). Out of those7,373 dogs, 64 died due to PHMT, which corresponds to
0.9% of the dogs dying from any cause in the period; 7.8% of dogs which deaths were caused
by tumors in general; and 33.5% of all dogs dying from hepatic tumors (primary and
metastatic). Out of the 64 cases of PHMT, 51 were reviewed histologically and evaluated by
immunohistochemistry; from these cases, 46 were carcinomas (36 cholangiocarcinomas, 9
hepatocellular carcinomas and one hepatocholangiocarcinoma) and five were sarcomas (5
hemangiosarcomas). In those dogs in which the age was possible determined, 64.7%
(cholangiocarcinomas) and 77.8% (hepatocellular carcinomas) were old. At necropsy
examination cholangiocarcinomas were characterized mainly by a multinodular pattern
(83.3%) while hepatocellular carcinomas occurred both as massive (44.4%) or multinodular
(44.4%) distribution. Extra-hepatic metastasis occurred respectively in 77.8% and 33.3% of
the cases of cholangiocarcinomas and hepatocellular carcinomas; metastatic
cholangiocarcinomas affected mainly the lungs (52.8%), lymph nodes (50%) and peritoneum
(19.4%). Ascites (22.2%) and icterus (22.2%) were observed frequently associated to both
tumors. Histologically, most part of the cholangiocarcinomas (86.1%) and of the
hepatocellular carcinomas (55.6%) presented respectively a tubular or trabecular type.
Immunohistochemistry revealed that the majority (63.9%) of cholangiocarcinomas was
positive for CK7 and none was marked for Hep Par 1. The majority (55.6%) of the
hepatocellular carcinomas revealed positive reaction for Hep Par 1 and none was marked for
CK7. The results presented here demonstrated a very high prevalence of PHMT, especially
cholangiocarcinomas, in the dog. The necropsy, histological and immunohistochemical
findings reported might be useful to help veterinary pathologists in the diagnosis of this
common form of cancer in dogs of the Rio Grande do Sul, Brazil. / Os tumores hepáticos malignos primários (THMP) representam uma importante causa
de morte de cães na rotina do Laboratório de Patologia Veterinária da Universidade Federal
de Santa Maria (LPV-UFSM). Diante disso, a prevalência e os aspectos epidemiológicos,
anatomopatológicos e imuno-histoquímicos dos THMP em cães foram estudados. De 7.373
cães necropsiados entre 1965 e 2012 (48 anos), 64 morreram de THMP. Esse número
corresponde a 0,9% das causas de morte de cães, 7,8% das causas de morte de cães por
tumores em geral e 33,5% das causas de morte de cães por tumores hepáticos. Desses 64
casos de THMP, 51 foram revistos histologicamente e avaliados imuno-histoquimicamente,
dos quais 46 eram carcinomas (colangiocarcinomas [n=36], carcinomas hepatocelulares [n=9]
e hepatocolangiocarcinoma [n=1]) e cinco eram sarcomas (hemangiossarcomas [n=5]). Dos
cães com colangiocarcinomas e carcinomas hepatocelulares em que a idade estava disponível
nos protocolos, 64,7% e 77,8% eram idosos, respectivamente. Na necropsia,
colangiocarcinomas caracterizaram-se principalmente por ocorrerem em um padrão
multinodular (83,3%), enquanto carcinomas hepatocelulares ocorreram tanto de forma
massiva (44,4%) quanto multinodular (44,4%). Metástases extra-hepáticas foram vistas em
77,8% e 33,3% dos casos de colangiocarcinomas e carcinoma hepatocelulares,
respectivamente, e em relação aos colangiocarcinomas afetaram principalmente pulmões
(52,8%), linfonodos (50%) e peritônio (19,4%). Ascite (22,2%) e icterícia (22,2%) foram
achados associados ocasionalmente com ambos os tumores. Na histologia, a maior parte dos
colangiocarcinomas (86,1%) e dos carcinomas hepatocelulares (55,6%) tinha padrão tubular e
trabecular, respectivamente. Na imuno-histoquímica, a maioria (63,9%) dos
colangiocarcinomas demonstrou imunomarcação para CK7 e nenhum imunomarcou para Hep
Par 1. A maioria (55,6%) dos carcinomas hepatocelulares demonstrou imunomarcação para
Hep Par 1 e nenhum imunomarcou para CK7. Os resultados aqui apresentados demonstram
uma alta prevalência de THMP, principalmente colangiocarcinomas, e servem para auxiliar,
através dos achados de necropsia, histologia e imuno-histoquímica, patologistas veterinários
no diagnóstico dessa forma tão comum de câncer em cães da Região Central do RS, Brasil.
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Spiral-CT zur Diagnostik fokaler LeberläsionenKopka, Lars 17 July 2001 (has links)
Zur Optimierung der Diagnostik fokaler Leberläsionen mittels Spiral-CT, einschließlich der Mehrschicht-Technik, wurden methodische Aspekte evaluiert und experimentelle Untersuchungen durchgeführt. Die erzielten Ergebnisse konnten anschließend in klinischen Studien überprüft werden. Es stellte sich dabei heraus, daß die diagnostische Aussagekraft der Spiral-CT der Leber erheblich von den angewendeten Untersuchungsparametern wie Schichtdicke, Pitchfaktor, Rekonstruktionsintervall und Röhrenstrom abhängig ist. Diese sollten optimal aufeinander abgestimmt werden, um ein möglichst hohes Kontrast-zu Rausch Verhältnis von Läsionen zum umgebenden Leberparenchym zu erreichen. Ein weiterer wesentlicher methodischer Aspekt war die intravenöse Gabe eines jodhaltigen Kontrastmittels. Hier zeigte sich insbesondere die zeitliche Anpassung des Kontrastmittelbolus an den Start der CT-Untersuchung als bedeutsam. Es wurden diesbezüglich verschiedene Verfahren entwickelt und überprüft. Dabei erwies sich in experimentellen und klinischen Untersuchungen eine spezielle CT-Software zum semiautomatischen Bolustracking als besonders erfolgreich und stellt den derzeitig anerkannten Referenzstandard dar. Die Untersuchung der Leber in mehreren Perfusionsphasen, der sog. arteriellen und der portalvenösen Phase war bei Patienten mit hypervaskularisierten Tumoren besonders sensitiv und spezifisch, wohingegen sich bei hypovaskularierten Leberläsionen die alleinige portalvenöse Phase als ausreichend erwiesen hatte. Auf die Nativuntersuchung kann bei der Leberdiagnostik generell verzichtet werden. Die Spiral-CT erwies sich nach entsprechenden Optimierungsschritten, insbesondere nach Etablierung der Mehrschicht-Spiral-CT, als ein hervorragendes Verfahren für die Diagnostik fokaler Leberläsionen. / Different methodological aspects and experimental studies were performed for the optimization of the diagnostics of focal liver lesions with helical CT including the multi-slice technique. The obtained results were evaluated in successive clinical examinations. The diagnostic impact of helical CT was substantially influenced by various CT scan parameters such as slice thickness, pitch factor, reconstruction interval and tube current. These parameters should be ideally adapted for a sufficiently high contrast-to-noise ratio of liver lesions in respect to the surrounding parenchyma. The intravenous administration of iodinated contrast material was another important feature. Especially the tailoring of the contrast material bolus to the start of the CT scan was essential. Different techniques were developed and evaluated for this reason. In experimental and clinical studies a specially developed CT software for a semiautomatic bolus-tracking proved to be successful and represents the current standard of reference. The examination of the liver in different perfusion phases, eg. arterial and portal venous phase, was very sensitive and specific in patients with hypervascular liver tumors while the portalvenous phase alone was sufficient for hypovascular liver lesions. The unenhanced CT series could be omitted in all instances. Helical CT, especially after introduction of the multi-slice technique proved to be a very effective diagnostic tool for the evaluation of focal liver lesions.
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Procesų, įtakojančių radiodažninės abliacijos kepenų audinyje rezultatus, tyrimas / The investigation of the processes influencing the results of radiofrequency ablation in the liver tissueVanagas, Tomas 01 June 2011 (has links)
Vienas iš būdų padėti pacientams, sergantiems kepenų navikais, yra lokalus naviko sunaikinimas radiodažnine abliacija. Pagrindine šio metodo problema išlieka aukštas naviko atkryčio dažnis. Disertacijos tikslas yra ištirti procesus, vykstančius radiodažnine abliacija paveiktame kepenų audinyje, išsiaiškinti šių procesų mechanizmus bei hipertermijos sąlygojamus pakitimus audinio, ląstelės ir subląsteliniame lygmenyje. Retrospektyviu tyrimu įvertintas pacientų, kuriems KMUK Chirurgijos klinikoje buvo atlikta kepenų navikų radiodažninė abliacija, navikų atkryčio dažnis, jo atsiradimo laikas ir veiksniai, galintys sąlygoti atkrytį. Eksperimentiškai įvertinti fizikiniai veiksniai, sąlygojantys šilumos plitimą kepenų audinyje, jų įtaka kepenų audinio pažeidimo mąstui ir tolygumui. Nustatyti morfologiniai ir biocheminiai pakitimai, vykstantys pereinamojoje kepenų audinio pažeidimo zonoje, bei šių pakitimų atsiradimo laikas. Ištirti pereinamosios kepenų audinio pažeidimo zonos hepatocitų mitochondrijų funkcijų pokyčiai ir apoptozės proceso vyksmui reikalingų energetinių resursų susidarymas, eksperimentiškai modeliuojant šios zonos temperatūrinius kitimus. Tyrimo naujumą lemia tai, kad darbe nustatyta jog apoptozės procesas pereinamoje radiodažninio pažeidimo zonoje gali būti nustatomas praėjus valandai po terminio pažeidimo. Eksperimentuose su hepatocitų mitochondrijomis nustatėme iki šiol neaprašytą neigiamą hipertermijos poveikį kepenų ląstelių mitochondrijų funkciniams rodikliams. / Radiofrequency ablation is one of the most widely accepted method for the local ablation of liver tumors. One of the negative aspects of this method is a high local recurrence rate, which is associated with the worse survival. The aim of the dissertation was to explore the processes in radiofrequency ablation affected liver tissue, ascertain the mechanisms of these processes and hyperthermia induced changes in the liver tissue, cells and subcellular level. The liver tumor recurrence rate, time and factors that could determine the recurrence were estimated using retrospective analysis of data. The physical parameters determining the spreading of the heat in liver tissue in experimental model and the influence of these parameters on extent and homogeneity of the damage were determined. The morphological and biochemical changes in the remote from the heat source zone were determined and the time of these changes was detected. The changes of liver cells mitochondria functions and the intracellular formation of energy resources necessary for these processes in subcellular level (apoptosis) were investigated simulating temperature changes in experimental model. The scientific novelty was governed by the data those support the activation of apoptotic pathway in the early period after exposure to hyperthermia. Our experimental study revealed yet unpublished data of the adverse effects of hyperthermia on the key functional parameters of the mitochondria.
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Modélisation d'un système de navigation chirurgicale pour le traitement par radio-fréquences des tumeurs du foie / Development of a Computer Assisted System aimed at RFA Liver SurgeryMundeleer, Laurent L 24 September 2009 (has links)
Radiofrequency ablation (RFA) is a minimally invasive treatment for either hepatocellular carcinoma or metastasis liver carcinoma. In order to resect large lesions, the surgeon has to perform multiple time-consuming destruction cycles and reposition the RFA needle for each of them. The critical step in handling a successful ablation and preventing local recurrence is the correct positioning of the needle. For small tumors, the surgeon places the middle of the active needle tip in the center of the tumor under intra-operative ultrasound guidance. When one application is not enough to cover the entire tumor, the surgeon needs to repeat the treatment after repositioning of the needle, but US guidance is obstructed by the opacity stemming from the first RFA application. In this case the surgeon can only rely on anatomical knowledge and the repositioning of the RFA needle becomes a subjective task limiting the treatment accuracy. We have developed a computer assisted surgery guidance application for this repositioning procedure. Our software application handles the complete process from preoperative image analysis to tool tracking in the operating room. Our framework is mostly used for this RFA procedure, but is also suitable for any other medical or surgery application.
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