48 research outputs found

    Intraoperative molecular fluorescence imaging of pancreatic cancer by targeting vascular endothelial growth factor: a multicenter feasibility dose-escalation study

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    Tumor visualization with near-infrared fluorescence (NIRF) imaging might aid exploration and resection of pancreatic cancer by visualizing the tumor in real time. Conjugation of the near-infrared fluorophore IRDye800CW to the monoclonal antibody bevacizumab enables targeting of vascular endothelial growth factor A. The aim of this study was to determine whether intraoperative tumor-specific imaging of pancreatic cancer with the fluorescent tracer bevacizumab-800CW is feasible and safe. Methods: In this multicenter dose-escalation phase I trial, patients in whom pancreatic ductal adenocarcinoma (PDAC) was suspected were administered bevacizumab-800CW (4.5, 10, or 25 mg) 3 d before surgery. Safety monitoring encompassed allergic or anaphylactic reactions and serious adverse events attributed to bevacizumab-800CW. Intraoperative NIRF imaging was performed immediately after laparotomy, just before and after resection of the specimen. Postoperatively, fluorescence signals on the axial slices and formalin-fixed paraffin-embedded tissue blocks from the resected specimens were correlated with histology. Subsequently, tumor-to-background ratios (TBR) were calculated. Results: Ten patients with clinically suspected PDAC were enrolled in the study. Four of the resected specimens were confirmed PDACs; other malignancies were distal cholangiocarcinoma, ampullary carcinoma, and neuroendocrine tumors. No serious adverse events were related to bevacizumab-800CW. In vivo tumor visualization with NIRF imaging differed per tumor type and was nonconclusive. Ex vivo TBRs were 1.3, 1.5, and 2.5 for the 4.5-, 10-, and 25-mg groups, respectively. Conclusion: NIRF-guided surgery in patients with suspected PDAC using bevacizumab-IRDye800CW is feasible and safe. However, suboptimal TBRs were obtained because no clear distinction between pancreatic cancer from normal or inflamed pancreatic tissue was achieved. Therefore, a more tumor-specific tracer than bevacizumab-IRDye800CWfor PDAC is preferred.Surgical oncolog

    Layer-by-layer technique to developing functional nanolaminate films with antifungal activity

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    The layer-by-layer (LbL) deposition method was used to build up alternating layers (five) of different polyelectrolyte solutions (alginate, zein-carvacrol nanocapsules, chitosan and chitosan-carvacrol emulsions) on an aminolysed/charged polyethylene terephthalate (A/C PET) film. These nanolaminated films were characterised by contact angle measurements and through the determination of water vapour (WVTR) and oxygen (O2TR) transmission rates. The effect of active nanolaminated films against the Alternaria sp. and Rhizopus stolonifer was also evaluated. This procedure allowed developing optically transparent nanolaminated films with tuneable water vapour and gas properties and antifungal activity. The water and oxygen transmission rate values for the multilayer films were lower than those previously reported for the neat alginate or chitosan films. The presence of carvacrol and zein nanocapsules significantly decreased the water transmission rate (up to 40 %) of the nanolaminated films. However, the O2TR behaved differently and was only improved (up to 45 %) when carvacrol was encapsulated, i.e. nanolaminated films prepared by alternating alginate with nanocapsules of zein-carvacrol layers showed better oxygen barrier properties than those prepared as an emulsion of chitosan and carvacrol. These films containing zein-carvacrol nanocapsules also showed the highest antifungal activity (30 %), which did not significantly differ from those obtained with the highest amount of carvacrol, probably due to the controlled release of the active agent (carvacrol) from the zein-carvacrol nanocapsules. Thus, this work shows that nanolaminated films prepared with alternating layers of alginate and zein-carvacrol nanocapsules can be considered to improve the shelf-life of foodstuffs.The authors acknowledge financial support from FP7 IP project BECOBIOCAP^. M. J. Fabra is recipients of a Juan de la Cierva contract from the Spanish Ministry of Economy and Competitivity. Maria L. Flores-López thanks Mexican Science and Technology Council (CONACyT, Mexico) for PhD fellowship support (CONACyT Grant Number 215499/310847). The author Miguel A. Cerqueira is a recipient of a fellowship (SFRH/BPD/72753/2010) supported by Fundação para a Ciência e Tecnologia, POPH-QREN and FSE (FCT, Portugal). The authors also thank the FCT Strategic Project of UID/ BIO/04469/2013 unit, the project RECI/BBB-EBI/0179/2012 (FCOMP- 01-0124-FEDER-027462) and the project BBioInd - Biotechnology and Bioengineering for improved Industrial and Agro-Food processes,^ REF. NORTE-07-0124-FEDER-000028 Co-funded by the Programa Operacional Regional do Norte (ON.2–O Novo Norte), QREN, FEDER. The support of EU Cost Action FA0904 is gratefully acknowledged

    Targeted next-generation sequencing has incremental value in the diagnostic work-up of patients with suspect pancreatic masses: a multi-center prospective cross sectional study

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    BackgroundThe diagnostic process of patients with suspect pancreatic lesions is often lengthy and prone to repeated diagnostic procedures due to inconclusive results. Targeted Next-Generation Sequencing (NGS) performed on cytological material obtained with fine needle aspiration (FNA) or biliary duct brushing can speed up this process. Here, we study the incremental value of NGS for establishing the correct diagnosis, and subsequent treatment plan in patients with inconclusive diagnosis after regular diagnostic work-up for suspect pancreatic lesions.Methods In this prospective cross-sectional cohort study, patients were screened for inclusion in four hospitals. NGS was performed with AmpliSeq Cancer Hotspot Panel v2 and v4b in patients with inconclusive cytology results or with an uncertain diagnosis. Diagnostic results were evaluated by the oncology pancreatic multidisciplinary team. The added value of NGS was determined by comparing diagnosis (malignancy, cystic lesion or benign condition) and proposed treatment plan (exploration/resection, neoadjuvant chemotherapy, follow-up, palliation or repeated FNA) before and after integration of NGS results. Final histopathological analysis or a 6-month follow-up period were used as the reference standard in case of surgical intervention or non-invasive treatment, respectively.Results In 50 of the 53 included patients, cytology material was sufficient for NGS analysis. Diagnosis before and after integration of NGS results differed in 24% of the patients. The treatment plan was changed in 32% and the diagnosis was substantiated by the NGS data in 44%. Repetition of FNA/brushing was prevented in 14% of patients. All changes in treatment plan were correctly made after integration of NGS. Integration of NGS increased overall diagnostic accuracy from 68% to 94%.Interpretation This study demonstrates the incremental diagnostic value of NGS in patients with an initial inconclusive diagnosis. Integration of NGS results can prevent repeated EUS/FNA, and can also rigorously change the final diagnosis and treatment plan.Surgical oncolog

    Application of project management methodologies in the execution of medical gases installations to improve synergy within South African hospitals

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    Abstract: This minor dissertation studies the application of project management methodologies in the execution of medical gases installations within South African hospitals. This was done in order to improve synergy during the execution of the medical gases installation with the rest of the hospital build programme. Medical gases installation in general as a gas reticulation system is made up of a combination of equipment that together or as individually are used to transmit medical gases for medicinal use in hospitals. These are gases that are regarded as life supporting within the hospital operations. They are not only used for healing or curing diseases but are used to support processes/machines that perform such functions. The installations are expected to be designed, installed and commissioned to meet the minimum requirements of SANS 7396-1/2, SANS 10260, EIGA guides and SANS 347-PER. South African National Standards (SANS) 7396 part 1 deals with the pipeline system for compressed medical gases and vacuum and part 2 deals with Anaesthetic gas scavenging disposal system. SANS 10260 deals with the supply and storage of cryogenic gases in South Africa, HTM and EIGA describes the general scientific considerations of gas behaviour and what to consider during designing of a safe gas system. The supplied gas is produced as a cryogenic gas in a liquid form from atmospheric air through an air separation unit process of distillation. It is however packaged in a vapour form in cylinders or directly in a bulk liquid storage tank and using a vaporizer is converted into vapour. According to SANS requirements, three sources of supply are required for each gas reticulation supply system in a hospital. Medical gases installations by their nature are projects and should follow project management doctrines in order to execute them in a manner that is acceptable and satisfies customer requirements. According to PMBOK, a project is not a fixed endeavour that gets to be undertaken, it is a short term activity that is aimed to create a unique product, service or end result. As this principle applies with the type of installations carried out in supplying and installing reticulation systems that transmit medical gases to the hospitals point of use such as theatres, ICU’s, wards etc. As result of the nature of the medical gases reticulation system, the study aims to bring to the sector project management principles to ensure this critical task is always executed safely and within acceptable best practice.M.Phil. (Engineering Management
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