Safe Procedure for Efficient Hydrodynamic Gene Transfer to Isolated Porcine Liver in Transplantation.

Although calcineurin inhibitors are very effective as immunosuppressants in organ transplantation, complete graft acceptance remains as a challenge. Transfer of genes with immunosuppressant functions could contribute to improving the clinical evolution of transplantation. In this sense, hydrodynamic injection has proven very efficacious for liver gene transfer. In the present work, the hIL-10 gene was hydrofected 'ex vivo' to pig livers during the bench surgery stage, to circumvent the cardiovascular limitations of the procedure, in a model of porcine orthotopic transplantation with a 10-day follow-up. We used IL-10 because human and porcine proteins can be differentially quantified and for its immunomodulatory pleiotropic functions. Safety (biochemical parameters and histology), expression efficacy (RNA transcription and blood protein expression), and acute inflammatory response (cytokines panel) of the procedure were evaluated. The procedure proved safe as no change in biochemical parameters was observed in treated animals, and human IL-10 was efficaciously expressed, with stationary plasma protein levels over 20 pg/mL during the follow-up. Most studied cytokines showed increments (interferon-α, IFN-α; interleukin-1ß, IL-1ß; tumor necrosis factor α, TNFα; interleukin-6, IL-6; interleukin-8, IL-8; interleukin-4, IL-4; and transforming growth factor-ß, TGF-ß) in treated animals, without deleterious effects on tissue. Collectively, the results support the potential clinical interest in this gene therapy model that would require further longer-term dose-response studies to be confirmed.

Functional Diversity in Radiolabeled Nanoceramics and Related Biomaterials for the Multimodal Imaging of Tumors.

Nanotechnology advances have the potential to assist toward the earlier detection of diseases, giving increased accuracy for diagnosis and helping to personalize treatments, especially in the case of noncommunicative diseases (NCDs) such as cancer. The main advantage of nanoparticles, the scaffolds underpinning nanomedicine, is their potential to present multifunctionality: synthetic nanoplatforms for nanomedicines can be tailored to support a range of biomedical imaging modalities of relevance for clinical practice, such as, for example, optical imaging, computed tomography (CT), magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and positron emission tomography (PET). A single nanoparticle has the potential to incorporate myriads of contrast agent units or imaging tracers, encapsulate, and/or be conjugated to different combinations of imaging tags, thus providing the means for multimodality diagnostic methods. These arrangements have been shown to provide significant improvements to the signal-to-noise ratios that may be obtained by molecular imaging techniques, for example, in PET diagnostic imaging with nanomaterials versus the cases when molecular species are involved as radiotracers. We surveyed some of the main discoveries in the simultaneous incorporation of nanoparticulate materials and imaging agents within highly kinetically stable radio-nanomaterials as potential tracers with (pre)clinical potential. Diversity in function and new developments toward synthesis, radiolabeling, and microscopy investigations are explored, and preclinical applications in molecular imaging are highlighted. The emphasis is on the biocompatible materials at the forefront of the main preclinical developments, e.g., nanoceramics and liposome-based constructs, which have driven the evolution of diagnostic radio-nanomedicines over the past decade.

Corrigendum: Nano-Theranostics for the Sensing, Imaging and Therapy of Prostate Cancers.

[This corrects the article DOI: 10.3389/fchem.2022.830133.].

Nano-Theranostics for the Sensing, Imaging and Therapy of Prostate Cancers.

We highlight hereby recent developments in the emerging field of theranostics, which encompasses the combination of therapeutics and diagnostics in a single entity aimed for an early-stage diagnosis, image-guided therapy as well as evaluation of therapeutic outcomes of relevance to prostate cancer (PCa). Prostate cancer is one of the most common malignancies in men and a frequent cause of male cancer death. As such, this overview is concerned with recent developments in imaging and sensing of relevance to prostate cancer diagnosis and therapeutic monitoring. A major advantage for the effective treatment of PCa is an early diagnosis that would provide information for an appropriate treatment. Several imaging techniques are being developed to diagnose and monitor different stages of cancer in general, and patient stratification is particularly relevant for PCa. Hybrid imaging techniques applicable for diagnosis combine complementary structural and morphological information to enhance resolution and sensitivity of imaging. The focus of this review is to sum up some of the most recent advances in the nanotechnological approaches to the sensing and treatment of prostate cancer (PCa). Targeted imaging using nanoparticles, radiotracers and biomarkers could result to a more specialised and personalised diagnosis and treatment of PCa. A myriad of reports has been published literature proposing methods to detect and treat PCa using nanoparticles but the number of techniques approved for clinical use is relatively small. Another facet of this report is on reviewing aspects of the role of functional nanoparticles in multimodality imaging therapy considering recent developments in simultaneous PET-MRI (Positron Emission Tomography-Magnetic Resonance Imaging) coupled with optical imaging in vitro and in vivo, whilst highlighting feasible case studies that hold promise for the next generation of dual modality medical imaging of PCa. It is envisaged that progress in the field of imaging and sensing domains, taken together, could benefit from the biomedical implementation of new synthetic platforms such as metal complexes and functional materials supported on organic molecular species, which can be conjugated to targeting biomolecules and encompass adaptable and versatile molecular architectures. Furthermore, we include hereby an overview of aspects of biosensing methods aimed to tackle PCa: prostate biomarkers such as Prostate Specific Antigen (PSA) have been incorporated into synthetic platforms and explored in the context of sensing and imaging applications in preclinical investigations for the early detection of PCa. Finally, some of the societal concerns around nanotechnology being used for the detection of PCa are considered and addressed together with the concerns about the toxicity of nanoparticles-these were aspects of recent lively debates that currently hamper the clinical advancements of nano-theranostics. The publications survey conducted for this review includes, to the best of our knowledge, some of the most recent relevant literature examples from the state-of-the-art. Highlighting these advances would be of interest to the biomedical research community aiming to advance the application of theranostics particularly in PCa diagnosis and treatment, but also to those interested in the development of new probes and methodologies for the simultaneous imaging and therapy monitoring employed for PCa targeting.

Biocompatible Probes Based on Rare-Earth Doped Strontium Aluminates with Long-Lasting Phosphorescent Properties for In Vitro Optical IMAGING.

In recent decades, the demand for biomedical imaging tools has grown very rapidly as a key feature for biomedical research and diagnostic applications. Particularly, fluorescence imaging has gained increased attention as a non-invasive, inexpensive technique that allows real-time imaging. However, tissue auto-fluorescence under external illumination, together with a weak tissue penetration of low wavelength excitation light, largely restricts the application of the technique. Accordingly, new types of fluorescent labels are currently being investigated and, in this search, phosphorescent nanoparticles promise great potential, as they combine the interesting size-dependent properties of nanoscale materials with a long-lasting phosphorescence-type emission that allows optical imaging well after excitation (so avoiding autofluorescence). In this work, core-shell structures consisting of SrAlO:Eu,Dy luminescent cores encapsulated within a biocompatible silica shell were prepared, showing a green persistent phosphorescence with an afterglow time of more than 1000 s. A high-energy ball milling procedure was used to reduce the size of the starting phosphors to a size suitable for cellular uptake, while the silica coating was produced by a reverse micelle methodology that eventually allows the excitation and emission light to pass efficiently through the shell. Confocal fluorescence microscopy using HeLa cancer cells confirmed the potential of the all-ceramic composites produced as feasible labels for in vitro optical imaging.

Hybrid Hierarchical Heterostructures of Nanoceramic Phosphors as Imaging Agents for Multiplexing and Living Cancer Cells Translocation.

Existing fluorescent labels used in life sciences are based on organic compounds with limited lifetime or on quantum dots which are either expensive or toxic and have low kinetic stability in biological environments. To address these challenges, luminescent nanomaterials have been conceived as hierarchical, core-shell structures with spherical morphology and highly controlled dimensions. These tailor-made nanophosphors incorporate Ln:YVO4 nanoparticles (Ln = Eu(III) and Er(III)) as 50 nm cores and display intense and narrow emission maxima centered at ∼565 nm. These cores can be encapsulated in silica shells with highly controlled dimensions as well as functionalized with chitosan or PEG5000 to reduce nonspecific interactions with biomolecules in living cells. Confocal fluorescence microscopy in living prostate cancer cells confirmed the potential of these platforms to overcome the disadvantages of commercial fluorophores and their feasibility as labels for multiplexing, biosensing, and imaging in life science assays.

Laparoscopic versus open hemihepatectomy: comprehensive comparison of complications and costs at 90 days using a propensity method.

Laparoscopic hemihepatectomy (LHH) may offer advantages over open hemihepatectomy (OHH) in blood loss, recovery, and hospital stay. The aim of this study is to evaluate our recent experience performing hemihepatectomy and compare complications and costs up to 90 days following laparoscopic versus open procedures. Retrospective evaluation of patients undergoing hemihepatectomy at our center 01/2010-12/2018 was performed. Patient, tumor, and surgical characteristics; 90-day complications; and costs were analyzed. Inverse probability of treatment weighting (IPTW) was used to balance covariates. A total of 141 hemihepatectomies were included: 96 OHH and 45 LHH. While operative times were longer for LHH, blood loss and transfusions were less. At 90 days, there were similar rates of liver-specific and surgical complications but fewer medical complications following LHH. Medical complications that arose with greater frequency following OHH were primarily pulmonary complications and urinary and central venous catheter infections. Complications at 90 days were lower following LHH (Clavien-Dindo grade ≥ III OHH 23%, LHH 11%, p = 0.130; Comprehensive Complication Index OHH 20.0 ± 16.1, LHH 10.9 ± 14.2, p = 0.001). While operating costs were higher, costs for hospital stay and readmissions were lower with LHH. Patients undergoing LHH experience a significant reduction in postoperative medical complications and costs, resulting in 90-day cost equity compared with OHH.

Shedding Light Onto the Nature of Iron Decorated Graphene and Graphite Oxide Nanohybrids for CO2 Conversion at Atmospheric Pressure.

We report on the design and testing of new graphite and graphene oxide-based extended π-conjugated synthetic scaffolds for applications in sustainable chemistry transformations. Nanoparticle-functionalised carbonaceous catalysts for new Fischer Tropsch and Reverse GasWater Shift (RGWS) transformations were prepared: functional graphene oxides emerged from graphite powders via an adapted Hummer's method and subsequently impregnated with uniform-sized nanoparticles. Then the resulting nanomaterials were imaged by TEM, SEM, EDX, AFM and characterised by IR, XPS and Raman spectroscopies prior to incorporation of Pd(II) promoters and further microscopic and spectroscopic analysis. Newly synthesised 2D and 3D layered nanostructures incorporating carbon-supported iron oxide nanoparticulate pre-catalysts were tested, upon hydrogen reduction in situ, for the conversion of CO2 to CO as well as for the selective formation of CH4 and longer chain hydrocarbons. The reduction reaction was also carried out and the catalytic species isolated and fully characterised. The catalytic activity of a graphene oxide-supported iron oxide pre-catalyst converted CO2 into hydrocarbons at different temperatures (305, 335, 370 and 405 °C), and its activity compared well with that of the analogues supported on graphite oxide, the 3-dimensional material precursor to the graphene oxide. Investigation into the use of graphene oxide as a framework for catalysis showed that it has promising activity with respect to reverse gas water shift (RWGS) reaction of CO2 to CO, even at the low levels of catalyst used and under the rather mild conditions employed at atmospheric pressure. Whilst the γ-Fe2O3 decorated graphene oxide-based pre-catalyst displays fairly constant activity up to 405 °C, it was found by GC-MS analysis to be unstable with respect to decomposition at higher temperatures. The addition of palladium as a promoter increased the activity of the iron functionalised graphite oxide in the RWGS. The activity of graphene oxide supported catalysts was found to be enhanced with respect to that of iron-functionalised graphite oxide with, or without palladium as a promoter, and comparable to that of Fe@carbon nanotube-based systems tested under analogous conditions. These results display a significant step forward for the catalytic activity estimations for the iron functionalised and rapidly processable and scalable graphene oxide. The hereby investigated phenomena are of particular relevance for the understanding of the intimate surface morphologies and the potential role of non-covalent interactions in the iron oxide-graphene oxide networks, which could inform the design of nano-materials with performance in future sustainable catalysis applications.

The Impact of Direct-acting Antivirals on Overall Mortality and Tumoral Recurrence in Patients With Hepatocellular Carcinoma Listed for Liver Transplantation: An International Multicenter Study.

BACKGROUND: There is a lack of data on the use of direct-acting antivirals (DAA) on the risk of death and tumoral recurrence in patients with hepatitis C virus (HCV) and hepatocellular carcinoma (HCC) listed for liver transplantation (LT). We aimed to assess the impact of antiviral treatment on mortality and HCC recurrence patients with HCC-HCV. METHODS: This was a retrospective multicenter study of patients with HCC-HCV listed for LT from 2005 to 2015. Patients were divided according to the antiviral treatment received after HCC diagnosis: DAA, interferon (IFN), or no antiviral. Intention-to-treat overall survival and HCC recurrence incidence were compared by the Kaplan-Meier method. Multivariable regression analysis was performed to identify risk factors for outcomes. RESULTS: A total of 1012 HCV-HCC patients were listed for LT during the study period. The median follow-up was 4.0 (interquartile range = 2.3-6.7) years. Mortality was 5.6 (95% confidence interval [CI], 4.3-7.2), 13.1 (95% CI, 11.0-15.7), and 6.2 (95% CI, 5.4-7.2) deaths per 100 person-year among patients treated with DAA, IFN, and antiviral naïve, respectively (P < 0.001). Of the 875 HCV-HCC transplant recipients, the 5-year recurrence-free survival was 93.4%, 84.8%, 73.9% for the pre-LT DAA, pre-LT IFN, and antiviral naïve groups, respectively (P < 0.001). After multivariable regression, the use of pre-LT DAA was not associated to risk of recurrence (hazard ratio = 0.44 [95% CI, 0.19-1.00]). Post-LT DAA was not related to increased risk of recurrence (hazard ratio = 0.62 [95% CI, 0.33-1.16]). CONCLUSIONS: In this multicenter intent-to-treat study, DAA therapy was not found to be a risk factor for mortality or HCC recurrence after adjusting for potential confounders.

Proteomic investigation on bio-corona of Au, Ag and Fe nanoparticles for the discovery of triple negative breast cancer serum protein biomarkers.

Nowadays, there are no targeted therapeutic modalities for triple negative breast cancer (TNBC). This disease is associated with poor prognosis and worst clinical outcome because of the aggressive nature of the tumor, delayed diagnosis, and non-specific symptoms in the early stages. Therefore, identification of novel specific TNBC serum biomarkers for screening and therapeutic purposes remains an urgent clinical requirement. New user-friendly and cheap methods for biomarker identification are needed, and nanotechnology offers new opportunities. When dispersed in blood, nanoparticles (NPs) are covered by a protein shell termed "protein corona" (PC). While alterations in protein patterns are challeging to detect by conventional blood analyses, PC acts as a "nano-concentrator" of serum proteins with affinity for NPs' surface. So, the characterization of PC could allow the detection of otherwise undetectable changes in protein concentration at an early stage of the disease or after chemotherapy or surgery. To explore this research idea, serum samples from 8 triple negative breast cancer (TNBC) patients and 8 patients without malignancy were allowed to interact with gold nanoparticles (AuNPs: 10.02 ±â€¯0.91 nm), silver nanoparticles (AgNPs: 9.73 ±â€¯1.70 nm) and magnetic nanoparticles (MNPs: (9.30 ±â€¯0.67 nm). Here, in order to identify biomarker candidates in serum of TNBC patients, these nanomaterials were combined with electrophoretic separation (SDS-PAGE) to performed qualitative and quantitative comparisons of the serum proteomes of TNBC patients (n = 8) and healthy controls (n = 8) by liquid chromatography tandem-mass spectrometry (LC-MS/MS) analysis. The results were validated through a sequential window acquisition of all theoretical mass spectra (SWATH) analysis, performed in total serum samples (patients and controls) using this approach as a multiple reaction monitoring (MRM) analysis. SIGNIFICANCE: It is well known that several proteins presented in human serum are important biomarkers for the diagnosis or prognosis of different diseases, as triple negative breast cancer (TNBC). Determining how nanomaterials as gold nanoparticles (AuNPs: 10.02 ±â€¯0.91 nm), silver nanoparticles (AgNPs: 9.73 ±â€¯1.70 nm) and magnetic nanoparticles (MNPs: (9.30 ±â€¯0.67 nm) interact with human serum will assist not only in understanding their effects on the biological system (biocompability and toxicity), but also to obtain information for developing novel nanomaterials with high specificity and selectivity towards proteins with an important biological function (prognostic and diagnostic protein biomarkers).

Synthesis, Radiolabelling and In Vitro Imaging of Multifunctional Nanoceramics.

Molecular imaging has become a powerful technique in preclinical and clinical research aiming towards the diagnosis of many diseases. In this work, we address the synthetic challenges in achieving lab-scale, batch-to-batch reproducible copper-64- and gallium-68-radiolabelled metal nanoparticles (MNPs) for cellular imaging purposes. Composite NPs incorporating magnetic iron oxide cores with luminescent quantum dots were simultaneously encapsulated within a thin silica shell, yielding water-dispersible, biocompatible and luminescent NPs. Scalable surface modification protocols to attach the radioisotopes 64Cu (t1/2=12.7 h) and 68Ga (t1/2=68 min) in high yields are reported, and are compatible with the time frame of radiolabelling. Confocal and fluorescence lifetime imaging studies confirm the uptake of the encapsulated imaging agents and their cytoplasmic localisation in prostate cancer (PC-3) cells. Cellular viability assays show that the biocompatibility of the system is improved when the fluorophores are encapsulated within a silica shell. The functional and biocompatible SiO2 matrix represents an ideal platform for the incorporation of 64Cu and 68Ga radioisotopes with high radiolabelling incorporation.

Encapsulation of Cadmium Selenide Nanocrystals in Biocompatible Nanotubes: DFT Calculations, X-ray Diffraction Investigations, and Confocal Fluorescence Imaging.

The encapsulation of CdSe nanocrystals within single-walled carbon nanotube (SWNT) cavities of varying dimensions at elevated temperatures under strictly air-tight conditions is described for the first time. The structures of CdSe nanocrystals under confinement inside SWNTs was established in a comprehensive study, combining both experimental and DFT theoretical investigations. The calculated binding energies show that all considered polymorphs [(3:3), (4:4), and (4:2)] may be obtained experimentally. The most thermodynamically stable structure (3:3) is directly compared to the experimentally observed CdSe structures inside carbon nanotubes. The gas-phase DFT-calculated energy difference between "free" 3:3 and 4:2 structures (whereby 3:3 models a novel tubular structure in which both Cd and Se form three coordination, as observed experimentally for HgTe inside SWNT, and 4:2 is a motif derived from the hexagonal CuI bulk structure in which both Cd and Se form 4 or 2 coordination) is surprisingly small, only 0.06 eV per formula unit. X-ray powder diffraction, Raman spectroscopy, high-resolution transmission electron microscopy, and energy-dispersive X-ray analyses led to the full characterization of the SWNTs filled with the CdSe nanocrystals, shedding light on the composition, structure, and electronic interactions of the new nanohybrid materials on an atomic level. A new emerging hybrid nanomaterial, simultaneously filled and beta-d-glucan coated, was obtained by using pristine nanotubes and bulk CdSe powder as starting materials. This displayed fluorescence in water dispersions and unexpected biocompatibility was found to be mediated by beta-d-glucan (a biopolymer extracted from barley) with respect to that of the individual inorganic material components. For the first time, such supramolecular nanostructures are investigated by life-science techniques applied to functional nanomaterial characterization, opening the door for future nano-biotechnological applications.

Benefits of laparoscopic liver resection in patients with hepatocellular carcinoma and portal hypertension: a case-matched study.

BACKGROUND: The advantages of laparoscopy over open liver resection in patients with cirrhosis have been widely demonstrated. On the other hand, information on the role of minimally invasive liver surgery in the presence of clinically significant portal hypertension (CSPH) is scarce. The aim of this study was to evaluate the role of laparoscopic liver resection in selected cirrhotic patients with CSPH. METHODS: A retrospective case-control study of cirrhotic patients with hepatocellular carcinoma who were treated with laparoscopic liver resection was conducted from December 2005 to April 2016. A total of 45 patients were included. Patients were divided into two groups according to the presence or absence of clinically significant portal hypertension. Fifteen cirrhotic patients with CSPH were matched with 30 patients without CSPH. RESULTS: Overall, there were no differences in intraoperative results. No conversion to open surgery occurred in the CSPH group, and 3 patients were converted in the Non-CSPH group (0 vs. 10% p = 0.57). Only 2 (7%) patients in the Non-CSPH group and 1 (7%) in the CSPH group had relevant complications (modified Clavien-Dindo classification III). Two patients in the Non-CSPH group and one in the CSPH group developed transient ascites (7 vs. 7%). Postoperative hospital stay was similar in both groups, with a median of 4 days in the CSPH group and 3 days in the Non-CSPH group (p = 0.37). The median follow-up of the entire cohort was 38 months (range 7-100). Overall survival rates at 1 and 3 years were 100 and 87%, respectively. There was no significant difference between the groups in terms of survival (p = 0.8). CONCLUSION: This initial study showed that laparoscopic resection in patients with CSPH can be performed safely in well-selected patients and expand the current surgical indications in patients with CSPH. Prospective trials with a larger sample size are necessary to confirm these results.

Hepatic resection: a safe and effective surgery. / Resección hepática mayor: una cirugía segura y eficaz.

INTRODUCTION: We analyze major liver resections performed in 10 years, with the objective of evaluating perioperative results. As secondary objectives, factors related to major complications and comparative analyses of 25-year periods are evaluated. METHODS: Retrospective analysis of patients undergoing major hepatic resection (3 or more segments) from January 2005 to December 2014, from pre, intra and postoperative data. The Clavien classification is used for postoperative morbidity. RESULTS: A total of 416 major hepatectomies were performed. Transfusions were performed in 38 patients (9.1%). A Pringle maneuver was used in 47.7% of the cases. Half of the patients had no complications, and only 96 patients (23%) had a major complication. Bile leakage was the most frequent complication (n=72, 17.3% of patients), especially due to malignant disease and biliary reconstruction, high risk ASA (III-IV) and prolonged surgical time. Thirteen patients met criteria for liver failure, of which 7died (5 associated a bacterial infection). The mean hospital stay was 12.5 days, with an 11,8% readmission rate. When comparing 25-year periods, at present more complex patients are operated on, with a lower incidence of transfusions and complications (ns). CONCLUSIONS: Liver surgery has increased significantly in recent years. Surgical management of the liver now allows safe and effective surgery, with a very low complication rate. The limit of resectability depends on the residual hepatic volume.

Analysis of the long-term results of living donor liver transplantation in adults. / Análisis de los resultados a largo plazo del trasplante hepático de donante vivo en adulto.

INTRODUCTION: Living donor liver transplantation (LDLT) is an alternative to conventional transplantation given its excellent results. The aim of this study is to evaluate long-term outcomes in LDLT recipients. METHODS: 100 consecutive THDV recipients from the Hospital Clínic of Barcelona from March 2000 to October 2015 were included. The main indication for transplantation was end-stage liver disease (58%) followed by hepatocellular carcinoma (41%). 95% of grafts consisted of the right liver of the donor and the 5% of the left liver. RESULTS: After a median follow-up of 65.5 months, patient and graft survival at 1, 3, and 5 years was 93%, 80% and 74% and 90%, 76%, and 71%, respectively. The overall re-transplant rate was 9%. The most common long-term complication was biliary stenosis (40%) with an average time of onset of 13.5±12 months, with repeated admissions and an average of 1.9±2 endoscopic procedures and 3.5±3 Radiological procedures per patient. The definitive treatment was radiological dilation in 40% of cases, surgical intervention in 22.5% and re-transplantation in 7.5%. CONCLUSIONS: Given the long-term results, LDLT is confirmed as an alternative to conventional transplantation. However, the high rate of late biliary complications involves repeated admissions and invasive treatments that, while not compromising survival, can affect the patient's quality of life.

Applications of "Hot" and "Cold" Bis(thiosemicarbazonato) Metal Complexes in Multimodal Imaging.

The applications of coordination chemistry to molecular imaging has become a matter of intense research over the past 10 years. In particular, the applications of bis(thiosemicarbazonato) metal complexes in molecular imaging have mainly been focused on compounds with aliphatic backbones due to the in vivo imaging success of hypoxic tumors with PET (positron emission tomography) using (64) CuATSM [copper (diacetyl-bis(N4-methylthiosemicarbazone))]. This compound entered clinical trials in the US and the UK during the first decade of the 21(st) century for imaging hypoxia in head and neck tumors. The replacement of the ligand backbone to aromatic groups, coupled with the exocyclic N's functionalization during the synthesis of bis(thiosemicarbazones) opens the possibility to use the corresponding metal complexes as multimodal imaging agents of use, both in vitro for optical detection, and in vivo when radiolabeled with several different metallic species. The greater kinetic stability of acenaphthenequinone bis(thiosemicarbazonato) metal complexes, with respect to that of the corresponding aliphatic ATSM complexes, allows the stabilization of a number of imaging probes, with special interest in "cold" and "hot" Cu(II) and Ga(III) derivatives for PET applications and (111) In(III) derivatives for SPECT (single-photon emission computed tomography) applications, whilst Zn(II) derivatives display optical imaging properties in cells, with enhanced fluorescence emission and lifetime with respect to the free ligands. Preliminary studies have shown that gallium-based acenaphthenequinone bis(thiosemicarbazonato) complexes are also hypoxia selective in vitro, thus increasing the interest in them as new generation imaging agents for in vitro and in vivo applications.

Klatskin tumor: Diagnosis, preoperative evaluation and surgical considerations.

Hiliar cholangiocarcinoma is the most common type of cholangiocarcinoma, an represent around 10% of all hepatobiliary tumors. It is an aggressive malignancy, resectable in around 47% of the patients at diagnosis. Complete resection is the most effective and only potentially curative therapy, with a survival rate of less than 12 months in unresectable cases. Axial computerized tomography and magnetic resonance are the most useful image techniques to determine the surgical resectability. Clinically, jaundice and pruritus are the most common symptoms at diagnosis;preoperative biliary drainage is recommended using endoscopic retrograde cholangiography or percutaneous transhepatic cholangiography. Surgery using extended liver resections with an en bloc resection of the liver with vascular reconstruction is the technique with the highest survival. Complete resection with histologically negative resection margins (R0), nodal involvement and metastases are the most important prognostic factors.

Metallic nanoparticles as synthetic building blocks for cancer diagnostics: from materials design to molecular imaging applications.

Metallic nanoparticles have been a matter of intense exploration within the last decade due to their potential to change the face of the medical world through their role as 'nanotheranostics'. Their envisaged capacity to act as synthetic platforms for a multimodal imaging approach to diagnosis and treatment of degenerative diseases, including cancer, remains a matter of lively debate. Certain synthetic metal-based nanomaterials, e.g. gold and iron oxide nanoparticles, are already in clinical use or under advanced preclinical investigations following in vitro and in vivo preclinical imaging success. We surveyed the recent publications landscape including those reported metallic nanoparticles having established applications in vivo, as well as some of the new metallic nanoparticles which, despite their potential as cancer nanodiagnostics, are currently awaiting in vivo evaluation. The objective of this review is to highlight the current metallic nanoparticles and/or alloys as well as their derivatives with multimodal imaging potential, focusing on their chemistry as a springboard to discussing their role in the future of nanomedicines design. We also highlight here some of the fundamentals of molecular and nano-imaging techniques of relevance to the metal-based colloids, alloys and metallic nanoparticles discerning their future prospects as cancer nanodiagnostics. The current approaches for metallic and alloy surface derivatisation, aiming to achieve functional and biocompatible materials for multimodal bioimaging applications, are discussed in order to bring about some new perspectives on the efficiency of metallic nanoparticles as synthetic scaffolds for imaging probe design and forecast their future use in medical imaging techniques (optical, CT, PET, SPECT and MRI).

Results of laparoscopic radiofrequency ablation for HCC. Could the location of the tumour influence a complete response to treatment? A single European centre experience.

INTRODUCTION: In selected patients, radiofrequency ablation (RFA) is a well-established treatment for hepatocellular carcinoma (HCC). However, subcapsular or lesions close to adjacent viscera preclude a percutaneous approach. In this setting laparoscopic-RFA (LRFA) is a potential alternative. The aim of this study was to analyse the safety and feasibility of LRFA in patients with HCC. PATIENTS AND METHODS: Retrospective study of patients with HCC meeting strict inclusion criteria who underwent LRFA at a single Institution from December 2000 to March 2013. RESULTS: Forty-one patients underwent 42 LRFA of 51 nodules. The median size of the nodule was 2.5 (range 1.2-4.7) cm. Thirty-one tumours were subcapsular and 17 located near the gallbladder. Major complications occurred in 17 patients. The initial complete response (ICR) rate was 94% and was lower among tumours located adjacent to the gallbladder. At the end of the follow-up period, the sustained complete response (SCR) rate was 70% and was lower in tumours adjacent to the gallbladder while increased for subcapsular tumours. The 1-, 3- and 5-year overall survival rate was 92.6%, 64.5% and 43%, respectively. CONCLUSION: LRFA of HCC is safe, feasible and achieves excellent results in selected patients. LRFA should be the first-line technique for subcapsular lesions as it minimizes the risk of tumoural seeding and improves ICR. Proximity to gallbladder interferes in treatment efficacy (lower rate of ICR and lower rate of SCR).

Robot-assisted renal artery aneurysm repair with a saphenous vein Y-graft interposition.

BACKGROUND: Renal artery aneurysms (RAA) treatment includes both surgical repair and endovascular techniques, mostly depending on the location of aneurysm. For complex RAA located at renal artery bifurcation or distally, open surgical repair represents the gold standard of treatment. However, the transperitoneal open access to the renal artery requires a wide laparotomy--hence the attempt to be minimally invasive with the first reports of laparoscopic approach. Even if it represents a possibility, laparoscopy has not yet gained widespread acceptance for the technical difficulties in performing vascular anastomosis. We herein describe the repair of a complex RAA using the Da Vinci Surgical System. METHODS: A 41-year-old woman had an accidentally discovered saccular aneurysm of the right renal artery with a maximum diameter of 20 mm, with one in and four out. A laparoscopic robot-assisted approach was planned. Intraoperatively, we confirm the strategy to group the four output branches in two different patches. Thus, a Y-shaped autologous saphenous graft was prepared and introduced through a trocar. For the three anastomoses, a polytetrafluoroethylene running suture was preferred. RESULTS: The total operation time was 350 min, and the estimated surgical blood loss was about 200 ml. Warm ischemia time was 58 min for the posterior branch and 24 min for the second declamping. The patient resumed a regular diet on postoperative day 2, and the hospital stay lasted 4 days. No intraoperative or postoperative morbidity was noted. A CT scan performed 2 months later revealed the patency of all the reconstructed branches. CONCLUSIONS: The experience of our group counts five other renal aneurysm repair performed with a robot-assisted technique. The presence of five different arterial branches involved in the reconstruction makes this procedure difficult. Robot-assisted laparoscopic technique represents a valid alternative to open surgery in complex cases.