In vivo- und in vitro-Untersuchungen zur Immunantwort und Parasitenentwicklung bei Infektionen mit dem Darmparasiten Cryptosporidium parvum

Cryptosporidium parvum ist ein intrazellulärer protozoischer Darmparasit (Apikomplexa), der weltweit zu den bedeutendsten Erregern von Diarrhöen beim Menschen und einer Reihe von Nutztieren zählt. Vor allem immunkompromittierte Personen wie zum Beispiel AIDS-Patienten erleiden schwere, chronische bis lebensbedrohende Erkrankungen. Da nach wie vor keine effektive Therapie gegen eine Kryptosporidiose in Form eines spezifisch wirkenden Chemotherapeutikums oder einer Vakzine existiert, ist es notwendig, die Immunantwort des Wirtes gegen den Parasiten und dessen Bindung, Invasion und die intrazelluläre Entwicklung in den Epithelzellen eingehend zu studieren, um neue Ansatzpunkte zu entwickeln. Wohingegen Menschen zeitlebens suszeptibel für eine Infektion mit C. parvum sind, entwickeln Mäuse eine natürliche Resistenz und können als adulte Tiere nicht mehr infiziert werden. Daher sind Mausmodelle der Kryptosporidiose auf neonatale oder immunsupprimierte und immundefiziente adulte Mäuse beschränkt. Bei der Überwindung einer C. parvum-Infektion sind Effektoren der natürlichen und adaptiven Immunität beteiligt. Die zentrale Rolle spielen CD4+-T-Zellen, sowie Interferon-gamma und Interleukin-12. Im Rahmen dieser Arbeit wurden Infektionen in IFN-gamma (GKO)- und IL-12 p40 (IL12KO)-Knockout-Mäusen (C57BL/6) etabliert, für die bereits gezeigt wurde, dass sie eine Suszeptibilität gegenüber einer Erstinfektion besitzen. Erstmals wurden die beiden Infektionsmodelle parallel unter denselben Bedingungen analysiert, um Rückschlüsse auf die Funktion und die Bedeutung der beiden Th1-Zytokine IFN-gamma und IL-12 bei der Auseinandersetzung mit dem Parasiten und der Überwindung einer Infektion ziehen zu können. Es wurden deutliche Unterschiede im Infektionsverlauf, bei der Höhe und Dauer der Parasitenausscheidung und der induzierten systemischen und mukosalen Antikörperantwort beobachtet. Zum ersten Mal konnte gezeigt werden, dass neben IL12KO auch GKO in der Lage sind, eine erste Infektion zu überwinden und eine Resistenz gegenüber einer erneuten Konfrontation mit dem Parasiten zu entwickeln. Alle Ergebnisse deuten darauf hin, dass die Etablierung einer protektiven Immunität gegen eine Kryptosporidiose generell unabhängig von der Anwesenheit der Zytokine IFN-gamma und IL-12 ist, der Verlust von IFN-gamma jedoch schwerer wiegt. Bei GKO-Mäusen persistierte der Parasit in Form einer niedriggradigen chronischen Infektion. Die beiden Infektionsmodelle stellten sich als ideales System für die Etablierung einer effektiven Immunisierungsstrategie heraus. Intranasale Immunisierungen, welche neben einer systemischen auch eine mukosale Immunantwort induzieren können, schienen einen richtigen Ansatz darzustellen. Intraperitoneale und subkutane Immunisierungen führten zwar zur Ausbildung einer starken spezifischen IgG-Antwort im Serum, diese war jedoch nicht in der Lage, einen Schutz vor einer Infektion zu vermitteln. Neben den in vivo Untersuchungen wurde des Weiteren auch die intrazelluläre Entwicklung von C. parvum in einem in vitro Kultursystem verfolgt. Zum ersten Mal wurde die Genexpression von vier Oberflächenproteinen der invasiven Zoitenstadien und eines Oozystenwandproteins parallel durch RT-PCR analysiert. Es konnte gezeigt werden, dass alle untersuchten Gene während der intrazellulären Entwicklung differentiell exprimiert werden, was eine unterschiedliche Funktion der Proteine während des Entwicklungszyklus nahe legt. Das Expressionsmuster der verschiedenen Gene charakterisiert bestimmte Abschnitte innerhalb des Entwicklungszyklus. Dabei wurden Marker für die Invasion (CP17) sowie für die asexuelle (GP900) und sexuelle Replikation (COWP) identifiziert.

Fistola Artero-venosa Radio-Cefalica Distale per Emodialisi nel paziente anziano: Valutazione dei risultati ottenuti con l'utilizzo della Tecnica Microchirurgica

PREMESSA: Le linee guida raccomandano la fistola AV radio-cefalica autogena (RCAVF)come prima scelta per l'emodialisi. Preoccupazione è stata sollevata che questo potrebbe non essere appropriato nei pazienti anziani. METODO: Noi abbiamo seguito in modo prospettico 126 pazienti per tre anni. Dopo sistematica valutazione clinica ed ecografica, la RCAVF è stata creata utilizzando un microscopio operatore. La pervietà è stata valutata subito, a 1 settimana, a 1 mese e a 1 anno. I risultati sono stati registrati e stratificati in 2 gruppi: <70a e > 70a. RISULTATI: La RCAVF è stata creata nel 75% dei <70a e nel 70% dei >70a. L'incidenza di insuccesso immediato è stata 11% (<70a) e 13% (>70a). La pervietà primaria e secondaria ad 1 anno è stata 67% e 84% (<70a), 63% e 80% (>70a). CONCLUSIONI: La microchirurgia ha permesso la creazione di RCVAF in >70a con un rischio accettabile di fallimento e lievi differenze rispetto a <70a. L'età non deve precludere una creazione di RCAVF.

Evaluation of Microbial Contamination in Bivalve Mollusks: Epidemiology and Diagnosis

Shellfish are filter-feeding organisms that can accumulate many bacteria and viruses. Considering that depuration procedures are not effective in removal of certain microorganisms, shellfish-borne diseases are frequent in many parts of the world, and their control must rely primarily on investigation of prevalence of human pathogens in shellfish and water environment. However, the diffusion of enteric viruses and Vibrio bacteria is not known in many geographical areas, for example in Sardinia, Italy. A survey aimed at investigating the prevalence of Norovirus (NoV), hepatitis A virus (HAV), V. parahaemolyticus, V. cholerae and V. vulnificus was carried out, analyzing both local and imported purified, non-purified and retail shellfish from North Italy and Sardinia. Shellfish from both areas were found contaminated by NoVs, HAV and Vibrio, including retail and purified animals. Molecular analysis evidenced different NoV genogroups and genotypes, including bovine NoVs, as well as pathogenic Vibrio strains, underlining the risk for shellfish consumers. However, also other approaches are needed to control the diffusion of shellfish-borne diseases. It was originally thought that enteric viruses are passively accumulated by shellfish. Recently, it was proven that NoVs bind to specific carbohydrate ligands in oysters, and various NoV strains are characterized by a different bioaccumulation pattern. To deepen the knowledge on this argument, a study was carried out, analyzing bioaccumulation of up to 8 different NoV strains in four different species of shellfish. Different bioaccumulation patterns were observed for each shellfish species and NoV strain used, potentially important in setting up effective shellfish purification protocols. Finally, a novel study of evaluation of viral contamination in shellfish from the French Atlantic coast was carried out following the passage of Xynthia tempest over Western Europe which caused massive destruction. Different enteric viruses were found over a one month period, evidencing the potential of these events of contaminating shellfish.

New synthetic bile acid analogue agonists of FXR and TGR5 receptors: Analytical methodologies for the study of their physico-chemical properties, pharmacokinetic activity and metabolism.

This thesis reports an integrated analytical approach for the study of physicochemical and biological properties of new synthetic bile acid (BA) analogues agonists of FXR and TGR5 receptors. Structure-activity data were compared with those previous obtained using the same experimental protocols on synthetic and natural occurring BA. The new synthetic BA analogues are classified in different groups according also to their potency as a FXR and TGR5 agonists: unconjugated and steroid modified BA and side chain modified BA including taurine or glycine conjugates and pseudo-conjugates (sulphonate and sulphate analogues). In order to investigate the relationship between structure and activity the synthetic analogues where admitted to a physicochemical characterization and to a preliminary screening for their pharmacokinetic and metabolism using a bile fistula rat model. Sensitive and accurate analytical methods have been developed for the quali-quantitative analysis of BA in biological fluids and sample used for physicochemical studies. Combined High Performance Liquid Chromatography Electrospray tandem mass spectrometry with efficient chromatographic separation of all studied BA and their metabolites have been optimized and validated. Analytical strategies for the identification of the BA and their minor metabolites have been developed. Taurine and glycine conjugates were identified in MS/MS by monitoring the specific ion transitions in multiple reaction monitoring (MRM) mode while all other metabolites (sulphate, glucuronic acid, dehydroxylated, decarboxylated or oxo) were monitored in a selected-ion reaction (SIR) mode with a negative ESI interface by the following ions. Accurate and precise data where achieved regarding the main physicochemical properties including solubility, detergency, lipophilicity and albumin binding . These studies have shown that minor structural modification greatly affect the pharmacokinetics and metabolism of the new analogues in respect to the natural BA and on turn their site of action, particularly where their receptor are located in the enterohepatic circulation.

Ricerca di Escherichia coli produttori di verocitotossine e definizione di obiettivi di performance nella produzione primaria di alimenti di origine animale

La presenza di Escherichia coli produttori di verocitotossine (VTEC o STEC) rappresenta una tra le più importanti cause di malattia alimentare attualmente presenti in Europa. La sua presenza negli allevamenti di animali destinati alla produzione di alimenti rappresenta un importante rischio per la salute del consumatore. In conseguenza di comuni contaminazioni che si realizzano nel corso della macellazione, della mungitura i VTEC possono essere presenti nelle carni e nel latte e rappresentano un grave rischio se la preparazione per il consumo o i processi di lavorazione non comportano trattamenti in grado d’inattivarli (es. carni crude o poco cotte, latte non pastorizzato, formaggi freschi a latte crudo). La contaminazione dei campi coltivati conseguente alla dispersione di letame o attraverso acque contaminate può veicolare questi stipiti che sono normalmente albergati nell’intestino di ruminanti (domestici e selvatici) e anche prodotti vegetali consumati crudi, succhi e perfino sementi sono stati implicati in gravi episodi di malattia con gravi manifestazioni enteriche e complicazioni in grado di causare quadri patologici gravi e anche la morte. Stipiti di VTEC patogeni ingeriti con gli alimenti possono causare sintomi gastroenterici, con diarrea acquosa o emorragica (nel 50% dei casi), crampi addominali, febbre lieve e in una percentuale più bassa nausea e vomito. In alcuni casi (circa 5-10%) l’infezione gastroenterica si complica con manifestazioni tossiemiche caratterizzate da Sindrome Emolitico Uremica (SEU o HUS) con anemia emolitica, insufficienza renale grave e coinvolgimento neurologico o con una porpora trombotica trombocitopenica. Il tasso di mortalità dei pazienti che presentano l’infezione da E. coli è inferiore all’1%. I dati forniti dall’ECDC sulle infezioni alimentari nel periodo 2006-2010 hanno evidenziato un trend in leggero aumento del numero di infezioni a partire dal 2007. L’obiettivo degli studi condotti è quello di valutare la prevalenza ed il comportamento dei VTEC per una analisi del rischio più approfondita.

The C-4-Dicarboxylate carriers DcuB and DctA of Escherichia coli: function as cosensors and topology

Das fakultativ anaerobe Enterobakterium Escherichia coli nutzt C4-Dicarboxylate sowohl unter aeroben als auch anaeroben Bedingungen als Kohlenstoff- und Energiequelle. Die Aufnahme der C4-Dicarboxylaten und die Energiekonservierung mittels Fumaratatmung wird durch das Zweikomponentensystem DcuSR reguliert. Die Sensorhistidinkinase DcuS und der nachgeschaltete Responseregulator DcuR aktivieren bei Verfügbarkeit von C4-Dicarboxylaten die Expression der Gene für den Succinat Transporter DctA, den anaeroben Fumarat/Succinat Antiporter DcuB, die Fumarase B sowie die Fumaratreduktase FrdABCD. Die Transportproteine DctA und DcuB wiederum regulieren die Expression der DcuSR-abhängigen Gene negativ. Fehlen von DctA oder DcuB resultiert bereits ohne Effektor in einer maximalen Expression von dctA bzw. dcuB. Durch gerichtete und ungerichtete Mutagenese wurde gezeigt, dass die Transportfunktion des Carriers DcuB unabhängig von seiner regulatorischen Funktion ist. DcuB kann daher als Cosensor des DcuSR Systems angesehen werden.rnUnter Verwendung von Reportergenfusionen von C-terminal verkürzten Konstrukten von DcuB mit der Alkalischen Phosphatase und der β-Galactosidase wurde die Topologie des Multitransmembranproteins DcuB bestimmt. Zusätzlich wurde die Zugänglichkeit bestimmter Aminosäurereste durch chemische Modifikation mit membran-durchlässigen und membran-undurchlässigen Thiolreagenzien untersucht. Die erhaltenen Ergebnisse deuten auf die Existenz eines tief in die Membran reichenden, hydrophilen Kanal hin, welcher zum Periplasma hin geöffnet ist. Mit Hilfe der Topologie-Studien, des Hydropathie-Blots und der Sekundärstruktur-Vorhersage wurde ein Modell des Carriers erstellt. DcuB besitzt kurze, periplasmatisch liegende Proteinenden, die durch 12 Transmembranhelices und zwei große hydrophile Schleifen jeweils zwischen TM VII/VIII und TM XI/XII verbunden sind. Die regulatorisch relevanten Reste K353, T396 und D398 befinden sich innerhalb von TM XI sowie auf der angrenzenden cytoplasmatischen Schleife XI-XII. Unter Berücksichtigung der strukturellen und funktionellen Aspekte wurde ein Regulationsmodell erstellt, welches die gemeinsam durch DcuB und DcuS kontrollierte C4-Dicarboxylat-abhängige Genexpression darstellt. rnDer Effekt von DctA und DcuSR auf die Expression einer dctA´-´lacZ Reportergenfusion und auf die aerobe C4-Dicarboxylat-Aufnahme wurde untersucht. In-vivo FRET-Messungen weisen auf eine direkte Wechselwirkung zwischen dem Carrier DctA und dem Sensor DcuS hin. Dieses Ergebnis stützt die Theorie der Regulation von DcuS durch C4-Dicarboxylate und durch die Cosensoren DctA bzw. DcuB mittels direkter Protein-Protein Interaktion.rn

Nuove tecniche per il trattamento della malattia paranale di Crohn

Studio prospettico su 75 pazienti con malattia paranale di Crohn che ha come obiettivo quello di confrontare i risultati tra le nuove terapie medico-chirurgiche emergenti. La prima procedura è comune a tutti i pazienti e consiste in un intervento di incisione degli ascessi, fistulectomia e posizionamento di setoni di drenaggio nei tramiti fistolosi per il controllo della sepsi.Successivamente i pazienti vengono divisi in cinque gruppi e sottoposti ai trattamenti per la chiusura dei tramiti fistolosi: terapia sistemica con Infliximab,terapia sistemica con Adalimumab,confezionamento di Flap endoanale, instillazione di colla di fibrina o posizionamento di protesi biologiche. Abbiamo osservato una chiusura completa dei tramiti fistolosi nel 60% dei pazienti trattati con Infliximab, 53% di quelli trattati con Adalimumab, 40% di quelli in terapia con colla di fibrina, 80% di quelli sottoposti a Flap endoanale e 60% di quelli trattati con protesi biologiche. Gli ottimi risultati raggiunti in con le diverse metodiche di trattamento chirurgico locale rappresentano una valida alternativa alla terapia con farmaci biologici. Tali nuove metodiche risultano anzi fondamentali per il trattamento di quei pazienti che dopo una terapia con farmaci biologici non hanno raggiunto una completa risoluzione del quadro (rescue therapy). Terapia biologica e nuove tecniche chirurgiche risultano pertanto complementari, la prima contribuendo al miglioramento della qualità della mucosa del canale anale e del retto basso sulla quale risulta quindi più agevole agire con le seconde con una percentuale di successo sempre maggiore.

Semi-synthetic bile acids as novel drug candidate in liver diseases: physico-chemical characterization and HPLC-ES-MS/MS methods for their quali-quantitative analysis in different experimental animal models

The physico-chemical characterization, structure-pharmacokinetic and metabolism studies of new semi synthetic analogues of natural bile acids (BAs) drug candidates have been performed. Recent studies discovered a role of BAs as agonists of FXR and TGR5 receptor, thus opening new therapeutic target for the treatment of liver diseases or metabolic disorders. Up to twenty new semisynthetic analogues have been synthesized and studied in order to find promising novel drugs candidates. In order to define the BAs structure-activity relationship, their main physico-chemical properties (solubility, detergency, lipophilicity and affinity with serum albumin) have been measured with validated analytical methodologies. Their metabolism and biodistribution has been studied in “bile fistula rat”, model where each BA is acutely administered through duodenal and femoral infusion and bile collected at different time interval allowing to define the relationship between structure and intestinal absorption and hepatic uptake ,metabolism and systemic spill-over. One of the studied analogues, 6α-ethyl-3α7α-dihydroxy-5β-cholanic acid, analogue of CDCA (INT 747, Obeticholic Acid (OCA)), recently under approval for the treatment of cholestatic liver diseases, requires additional studies to ensure its safety and lack of toxicity when administered to patients with a strong liver impairment. For this purpose, CCl4 inhalation to rat causing hepatic decompensation (cirrhosis) animal model has been developed and used to define the difference of OCA biodistribution in respect to control animals trying to define whether peripheral tissues might be also exposed as a result of toxic plasma levels of OCA, evaluating also the endogenous BAs biodistribution. An accurate and sensitive HPLC-ES-MS/MS method is developed to identify and quantify all BAs in biological matrices (bile, plasma, urine, liver, kidney, intestinal content and tissue) for which a sample pretreatment have been optimized.

Investigation of different shellac grades and improvement of release from air suspension coated pellets

Shellac is the purified product of the natural polymer Lac. Shellac types, from different origins and with different ages, all purified by the solvent extraction process were compared in this study. Their physicochemical properties acid value, glass transition temperatures, color numbers and molecular sizes were determined. Metoprolol tartrate pellets were coated by air suspension coating with these different grades of shellac. Two coating levels 20% w/w and 25% w/w were applied and then subjected to in vitro dissolution testing. Enteric resistance was achieved for all tested brands for the two coating levels. At pH 6.8, 7.2 and 7.4, significant variations were obvious between the brands. rnMoreover the molecular size of shellac has a pronounced effect in that shellac types with larger molecular size show a higher and faster release than others, while the one with the smaller molecular size show the opposite effect on the release of metoprolol.rnIn this study commercially available ready for use aqueous shellac solutions (SSB AQUAGOLD), which are based on shellac SSB 57 (Dewaxed Orange Shellac, Bysakhi-Ber type refined in a solvent extraction process), with different manufacturing dates were used. rnTo improve the enteric coating properties of films from aqueous shellac solutions, different aqueous polymeric solutions of hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), carboyxmethyl cellulose (CMC), gum arabic and polysaccharides (Pullulan®) were used. These water soluble polymers will act as pore formers to enhance drug release from pellets coated with the combination of shellac and these polymers. The influence of these polymers on the gloss of the shellac films, mechanical properties of the films and drug release from metoprolol tartrate pellets were studied.rnThe potential of ethanol to alter the rate of drug release from shellac coated pellets was assessed by using a modified in vitro dose dumping in alcohol (DDA) method and the test concluded that shellac coated dosage forms can be co-administered with alcohol beverages containing ≤ 5% with no effect of alcohol on the shellac coat.rnPellets coated with shellac sodium salts, showed higher release rates than pellets coated with shellac as ammonium salt forms. rn

Fistole retto-vaginali Crohn-relate trattate mediante trasposizione del muscolo gracile: risultati a lungo termine e qualità della vita

OBIETTIVO: Le fistole retto-vaginali Crohn-relate hanno un impatto significativo sulla qualità della vita. Quando il canale anale è alterato da ulcerazioni e stenosi o in pazienti con difetti estesi del perineo, la chirurgia locale produce risultati insoddisfacenti. Lo scopo di questo studio è quello di valutare l'efficacia della trasposizione del muscolo gracile nelle fistole retto-vaginali Crohn-relate e determinare i suoi effetti sulla qualità della vita. MATERIALI E METODI: Da gennaio 2012 a ottobre 2014 sono state trattate 10 pazienti; sono state raccolte alcune variabili (età, BMI, il fumo, CDAI, setone perioperatorio, precedenti procedure, uso di immunomodulatori e steroidi). Tutte le pazienti sono state sottoposte ad ileostomia temporanea prima della graciloplastica. La percentuale di successo è stata misurata come numero di pazienti con fistola guarita dopo la chiusura della stomia. Sono stati utilizzati tre questionari prima della graciloplastica e 3 mesi dopo la chiusura della stomia al fine di valutare la qualità della vita (SF-36), l’ incontinenza fecale e la funzione sessuale. RISULTATI: La fistola retto-vaginale è stata chiusa in 9 pazienti su 10 dopo graciloplastica, con un follow-up medio di chiusura della stomia di 19 mesi (range 4 -34). È stata documentata una recidiva di RVF. Il tempo operatorio era 90-150 minuti (media, 120). La degenza postoperatoria era 7-16 giorni (media 10). Complicanze postoperatorie precoci includevano deiscenza delle suture perineali in 2 casi. Le complicanze a lungo termine includevano disestesia della cicatrice perineale. Nei dati post-operatori abbiamo riportato un miglioramento della qualità di vita, della funzione sessuale e della continenza fecale. CONCLUSIONI: La chiusura della fistola retto-vaginale utilizzando la trasposizione del muscolo gracile è associata a morbidità minima e un alto tasso di successo.

Refractory Hematuria in an Oliguric Patient After Pancreas Transplantation with Exocrine Pancreas Bladder Drainage

A 52-yr-old man presented with hematuria and clot retention. He had undergone simultaneous pancreas-kidney transplantation with exocrine pancreas bladder drainage 16 yr ago. The patient suffered from progressive transplant kidney failure with gradually decreasing urine output and needed hemodialysis every other day. Gross hematuria persisted after removal of all blood clots. Cystoscopy showed multiple small, flat ulcers of the bladder mucosa. Some bled discretely and were coagulated cautiously. However, hematuria was refractory to multiple urological interventions, which eventually necessitated an enteric diversion of the exocrine pancreas. Hematuria ceased following an uneventful postoperative course.

Primary tuberculosis of the TMJ: presentation of a case and literature review

Tuberculosis (TB) is a frequent health problem. The prevalence of extrapulmonary TB has increased in the last couple of years. Head and neck tuberculosis forms nearly 10% of all extrapulmonary manifestations of the disease. TB of the temporomandibular joint (TMJ) is rare; only a few cases have been reported. The clinical appearance of TB infection of the TMJ has been described as unspecific, resembling arthritis, osteomyelitis, cancer or any kind of chronic joint diseases. This article describes a 22-year-old woman with pain and left preauricular swelling. Magnetic resonance imaging and computed tomography showed an expansive process with destruction of the left condyle and condylar fossa. A fine needle aspiration examination of the swelling showed non-specific granulomatous inflammation. In the following days, a preauricular fistula developed, of which a swab and biopsy specimens were taken. Histological and microbiological examinations revealed an infection with Mycobacterium tuberculosis. The initial antituberculosis treatment consisted of a combination of four antibiotics and could be reduced to two antibiotics in the course of treatment. The treatment was completed successfully after 9 months.

The alphavbeta6 integrin is a highly specific immunohistochemical marker for cholangiocarcinoma

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are common primary hepatic malignancies. Their immunohistological differentiation using specific markers is pivotal for treatment and prognosis. We found alphavbeta6 integrin strongly upregulated in biliary fibrosis, but its expression in primary and secondary liver tumours is unknown. Here, we aimed to evaluate the diagnostic applicability of alphavbeta6 integrin in differentiating primary liver cancers.

A modified DRIL procedure by flow reversal of an aborted distal cephalic vein for critical hand ischaemia

Treatment of dialysis access-related hand ischaemia with preservation of the access remains an issue. We report the case of a patient presenting critical hand ischaemia 2 years after proximalisation of a distal radio-cephalic fistula with preservation of the original access. After valvulotomy, the distal cephalic vein was used as in situ bypass and directly anastomosed to the distal brachial artery, providing a direct flow to the hand. This procedure relieved the hand ischaemia without sacrificing the functioning fistula. Six months later, the fistula and bypass were still patent, showing that flow reversal of a previous fistula can be an efficient strategy to correct dialysis access-related hand ischaemia in selected cases.

A navigation system for open liver surgery: design, workflow and first clinical applications

The surgical treatment of liver tumours relies on precise localization of the lesions and detailed knowledge of the patient-specific vascular and biliary anatomy. Detailed three-dimensional (3D) anatomical information facilitates complete tumour removal while preserving a sufficient amount of functional liver tissue.