RESUMEN
Electrokinetic convection-enhanced delivery (ECED) utilizes an external electric field to drive the delivery of molecules and bioactive substances to local regions of the brain through electroosmosis and electrophoresis, without the need for an applied pressure. We characterize the implementation of ECED to direct a neutrally charged fluorophore (3 kDa) from a doped biocompatible acrylic acid/acrylamide hydrogel placed on the cortical surface. We compare fluorophore infusion profiles using ECED (time = 30 min, current = 50 µA) and diffusion-only control trials, for ex vivo (N = 18) and in vivo (N = 12) experiments. The linear intensity profile of infusion to the brain is significantly higher in ECED compared to control trials, both for in vivo and ex vivo. The linear distance of infusion, area of infusion, and the displacement of peak fluorescence intensity along the direction of infusion in ECED trials compared to control trials are significantly larger for in vivo trials, but not for ex vivo trials. These results demonstrate the effectiveness of ECED to direct a solute from a surface hydrogel towards inside the brain parenchyma based predominantly on the electroosmotic vector.
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Encéfalo , Convección , Sistemas de Liberación de Medicamentos , Hidrogeles , Hidrogeles/química , Encéfalo/metabolismo , Animales , Sistemas de Liberación de Medicamentos/instrumentación , Sistemas de Liberación de Medicamentos/métodos , Colorantes Fluorescentes/química , Colorantes Fluorescentes/administración & dosificación , Masculino , RatasRESUMEN
Indocyanine green is an FDA-approved fluorescent imaging dye used for determining cardiac output, hepatic function, liver blood flow, and retinal perfusion. It has been investigated preclinically in photoacoustic imaging and photothermal therapy (PTT); however, ICG photodegradation limits its biomedical applications. An aggregated form of ICG, known as J-aggregate (IJA), exhibits superior photoacoustic signals and thermal stability than the monomeric ICG. Nevertheless, IJA still suffers from low stability in the biological milieu, and short in vivo blood circulation. To address these limitations, a range of nanocarriers have been developed to enhance IJA stability and performance. This review focuses on IJA potentials and limitations, besides the recent development of IJA-loaded nanocarriers, particularly for cancer imaging and therapy.
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Verde de Indocianina , Nanomedicina Teranóstica , Verde de Indocianina/administración & dosificación , Humanos , Animales , Nanomedicina Teranóstica/métodos , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Neoplasias/diagnóstico por imagen , Nanopartículas , Colorantes Fluorescentes/química , Colorantes Fluorescentes/administración & dosificación , Técnicas Fotoacústicas/métodos , Portadores de Fármacos/químicaRESUMEN
5-Aminolevulinic Acid (5-ALA) is the only fluorophore approved by the FDA as an intraoperative optical imaging agent for fluorescence-guided surgery in patients with glioblastoma. The dosing regimen is based on rodent tests where a maximum signal occurs around 6 h after drug administration. Here, we construct a computational framework to simulate the transport of 5-ALA through the stomach, blood, and brain, and the subsequent conversion to the fluorescent agent protoporphyrin IX at the tumor site. The framework combines compartmental models with spatially-resolved partial differential equations, enabling one to address questions regarding quantity and timing of 5-ALA administration before surgery. Numerical tests in two spatial dimensions indicate that, for tumors exceeding the detection threshold, the time to peak fluorescent concentration is 2-7 h, broadly consistent with the current surgical guidelines. Moreover, the framework enables one to examine the specific effects of tumor size and location on the required dose and timing of 5-ALA administration before glioblastoma surgery.
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Ácido Aminolevulínico , Neoplasias Encefálicas , Simulación por Computador , Glioblastoma , Conceptos Matemáticos , Modelos Biológicos , Protoporfirinas , Cirugía Asistida por Computador , Glioblastoma/cirugía , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Glioblastoma/diagnóstico por imagen , Ácido Aminolevulínico/administración & dosificación , Humanos , Neoplasias Encefálicas/cirugía , Protoporfirinas/administración & dosificación , Protoporfirinas/metabolismo , Cirugía Asistida por Computador/métodos , Animales , Fármacos Fotosensibilizantes/administración & dosificación , Imagen Óptica/métodos , Colorantes Fluorescentes/administración & dosificaciónRESUMEN
Antitumor agents often lack effective penetration and accumulation to achieve high therapeutic efficacy in treating solid tumors. Nanomotor-based nanomaterials offer a potential solution to address this obstacle. Among them, nitric oxide (NO) based nanomotors have garnered attention for their potential applications in nanomedicine. However, there widespread clinical adoption has been hindered by their complex preparation processes. To address this limitation, we have developed a NO-driven nanomotor utilizing a convenient and scalable nanogel preparation procedure. These nanomotors, loaded with the fluorescent probe / sonosensitizer chlorin e6 (Ce6), were specifically engineered for sonodynamic therapy. Through comprehensive in vitro investigations using both 2D and 3D cell models, as well as in vivo analysis of Ce6 fluorescent signal distribution in solid tumor models, we observed that the self-propulsion of these nanomotors significantly enhances cellular uptake and tumor penetration, particularly in solid tumors. This phenomenon enables efficient access to challenging tumor regions and, in some cases, results in complete tumor coverage. Notably, our nanomotors have demonstrated long-term in vivo biosafety. This study presents an effective approach to enhancing drug penetration and improving therapeutic efficacy in tumor treatment, with potential clinical relevance for future applications.
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Clorofilidas , Nanogeles , Neoplasias , Óxido Nítrico , Porfirinas , Animales , Óxido Nítrico/administración & dosificación , Óxido Nítrico/metabolismo , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Neoplasias/metabolismo , Porfirinas/administración & dosificación , Porfirinas/farmacocinética , Línea Celular Tumoral , Nanogeles/química , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinética , Polietilenglicoles/química , Ratones Desnudos , Polietileneimina/química , Ratones Endogámicos BALB C , Colorantes Fluorescentes/química , Colorantes Fluorescentes/administración & dosificación , Femenino , Ratones , Terapia por Ultrasonido/métodos , Nanoestructuras/administración & dosificaciónRESUMEN
Cyanine derivatives are organic dyes widely used for optical imaging. However, their potential in longitudinal optoacoustic imaging and photothermal therapy remains limited due to challenges such as poor chemical stability, poor photostability, and low photothermal conversion. In this study, we present a new structural modification for cyanine dyes by introducing a strongly electron-withdrawing group (barbiturate), resulting in a new series of barbiturate-cyanine dyes (BC810, BC885, and BC1010) with suppressed fluorescence and enhanced stability. Furthermore, the introduction of BC1010 into block copolymers (PEG114-b-PCL60) induces aggregation-caused quenching, further boosting the photothermal performance. The photophysical properties of nanoparticles (BC1010-NPs) include their remarkably broad absorption range from 900 to 1200 nm for optoacoustic imaging, allowing imaging applications in NIR-I and NIR-II windows. The combined effect of these strategies, including improved photostability, enhanced nonradiative relaxation, and aggregation-caused quenching, enables the detection of optoacoustic signals with high sensitivity and effective photothermal treatment of in vivo tumor models when BC1010-NPs are administered before irradiation with a 1064 nm laser. This research introduces a barbiturate-functionalized cyanine derivative with optimal properties for efficient optoacoustics-guided theranostic applications. This new compound holds significant potential for biomedical use, facilitating advancements in optoacoustic-guided diagnostic and therapeutic approaches.
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Barbitúricos , Carbocianinas , Nanopartículas , Técnicas Fotoacústicas , Fototerapia , Animales , Técnicas Fotoacústicas/métodos , Carbocianinas/química , Carbocianinas/administración & dosificación , Nanopartículas/química , Barbitúricos/química , Barbitúricos/administración & dosificación , Fototerapia/métodos , Humanos , Ratones Endogámicos BALB C , Femenino , Ratones Desnudos , Línea Celular Tumoral , Colorantes Fluorescentes/química , Colorantes Fluorescentes/administración & dosificación , Ratones , Terapia Fototérmica/métodos , Neoplasias/terapiaRESUMEN
Measurement of glomerular filtration rate (GFR) is crucial in assessing kidney function status. Estimating GFR using clearance methodologies is cumbersome, as plasma and urinary concentrations and timed urine collections are required. Recently, a transcutaneous sensor has been developed whereby the rate of renal washout of a fluorescent marker administered intravenously allows calculation of GFR. The challenge is to ensure that the values of GFR obtained using the washout approach are in accord with those obtained conventionally.
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Tasa de Filtración Glomerular , Humanos , Colorantes Fluorescentes/administración & dosificación , Riñón/fisiopatología , Riñón/fisiología , Pruebas de Función Renal/métodos , Pruebas de Función Renal/normasRESUMEN
Lipid conjugates have advanced the field of lipid-based nanomedicine by promoting active-targeting (ligand, peptide, antibody), stability (PEGylation), controlled release (lipoid prodrug), and probe-based tracking (fluorophore). Recent findings indicate lipid conjugates dissociating from nanomedicine upon encountering a biological environment. Yet, implications for (pre)clinical outcomes remain unclear. In this study, using the zebrafish model (Danio rerio), we investigated the fate of liposome-incorporated lipid fluorophore conjugates (LFCs) after intravenous (IV) administration. LFCs having a bilayer mismatch and relatively polar fluorophore revealed counter-predictive outcomes for Caelyx/Doxil (clearance vs. circulating) and AmBisome-like liposomes (scavenger endothelial cell vs. macrophage uptake). Findings on LFC (mis)match for Caelyx/Doxil-like liposomes were supported by translational intravital imaging studies in mice. Importantly, contradicting observations suggest to originate from LFC dissociation in vivo, which was investigated by Asymmetric Flow Field-Flow Fractionation (AF4) upon liposome-serum incubation in situ. Our data suggests that LFCs matching with the liposome bilayer composition - that did not dissociate upon serum incubation - revealed improved predictive outcomes for liposome biodistribution profiles. Altogether, this study highlights the critical importance of fatty acid tail length and headgroup moiety when selecting lipid conjugates for lipid-based nanomedicine.
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Lípidos , Liposomas , Nanomedicina , Pez Cebra , Animales , Nanomedicina/métodos , Lípidos/química , Colorantes Fluorescentes/química , Colorantes Fluorescentes/administración & dosificación , Colorantes Fluorescentes/farmacocinética , Ratones , Polietilenglicoles/química , Polietilenglicoles/farmacocinética , Doxorrubicina/análogos & derivadosAsunto(s)
Hepatectomía , Laparoscopía , Neoplasias Hepáticas , Humanos , Laparoscopía/métodos , Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/diagnóstico por imagen , Cirugía Asistida por Computador/métodos , Fluorescencia , Pronóstico , Colorantes Fluorescentes/administración & dosificaciónRESUMEN
This study was the first attempt to visualize pulmonary retention of nanocarriers (NCs) with the use of the P2 probe, a new water-initiated aggregation-caused fluorescent-quenching (ACQ) dye, for the development of NCs with long-lasting retention in the respiratory system (RS). Flash nanoprecipitation was used to fabricate mucopenetrating NCs (MP/NCs) and mucoadhesive NCs (MA/NCs). Both NCs were labeled with the P2 probe, and their distribution and retention in RS were visualized after intratracheal administration to rats. MP/NCs and MA/NCs had a mean diameter below 200 nm and ζ-potential of 0 and 48 mV, respectively. MA/NCs showed three times stronger interactions with mucin than MP/NCs, resulting in significantly lower diffusiveness in mucus. The P2 probe exhibited an ACQ effect with negligible rekindling in simulated lung fluid, and the spectroscopic data suggested applicability to reliable imaging of insufflated NCs. In confocal laser scanning microscopic and in vivo imaging system images of the rat RS, MA/NCs were locally deposited in the respiratory tract and transported toward the pharynx by mucocilliary clearance (MCC). In contrast, MP/NCs diffused in the respiratory mucus were less subject to the influence of MCC. Based on the results from the bioimaging study using the P2 probe, MP/NCs could offer enhanced pulmonary retention of drugs compared with MA/NCs.
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Portadores de Fármacos , Nanopartículas , Animales , Ratas , Nanopartículas/química , Portadores de Fármacos/química , Masculino , Ratas Sprague-Dawley , Sistema Respiratorio/metabolismo , Sistema Respiratorio/efectos de los fármacos , Colorantes Fluorescentes/química , Colorantes Fluorescentes/administración & dosificaciónRESUMEN
BACKGROUND: For patients with peritoneal carcinomatosis, extent of disease and completeness of cytoreductive surgery (CRS) are major prognostic factors for long-term survival. Assessment of these factors could be improved using imaging agents. Pegsitacianine is a pH-sensitive polymeric micelle conjugated to the fluorophore indocyanine green. The micelle disassembles in acidic microenvironments, such as tumors, resulting in localized fluorescence unmasking. We assessed the utility of pegsitacianine in detecting residual disease following CRS. PATIENTS AND METHODS: NCT04950166 was a phase II, non-randomized, open-label, multicenter US study. Patients eligible for CRS were administered an intravenous dose of pegsitacianine at 1 mg/kg 24-72 h before surgery. Following CRS, the peritoneal cavity was reexamined under near-infrared (NIR) illumination to evaluate for fluorescent tissue. Fluorescent tissue identified was excised and evaluated by histopathology. The primary outcome was the rate of clinically significant events (CSE), defined as detection of histologically confirmed residual disease excised with pegsitacianine or a revision in the assessment of completeness of CRS. Secondary outcomes included acceptable safety and pegsitacianine performance. RESULTS: A total of 53 patients were screened, 50 enrolled, and 40 were evaluable for CSE across six primary tumor types. Residual disease was detected with pegsitacianine in 20 of 40 (50%) patients. Pegsitacianine showed high sensitivity and was well tolerated with no serious adverse events (SAEs). Transient treatment-related, non-anaphylactic infusion reactions occurred in 28% of patients. CONCLUSIONS: Pegsitacianine was well tolerated and facilitated the recognition of occult residual disease following CRS. The high rate of residual disease detected suggests that the use of pegsitacianine augmented surgeon assessment and performance during CRS.
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Procedimientos Quirúrgicos de Citorreducción , Verde de Indocianina , Neoplasia Residual , Neoplasias Peritoneales , Humanos , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/diagnóstico por imagen , Femenino , Persona de Mediana Edad , Masculino , Verde de Indocianina/administración & dosificación , Anciano , Concentración de Iones de Hidrógeno , Pronóstico , Adulto , Estudios de Seguimiento , Colorantes Fluorescentes/administración & dosificaciónRESUMEN
The widespread use of video-assisted thoracoscopic surgery (VATS) has triggered the rapid expansion in the field of computed tomography (CT)-guided preoperative localization and near-infrared (NIR) fluorescence image-guided surgery. However, its broader application has been hindered by the absence of ideal imaging contrasts that are biocompatible, minimally invasive, highly resolvable, and perfectly localized within the diseased tissue. To achieve this goal, we synthesize a dextran-based fluorescent and iodinated hydrogel, which can be injected into the tissue and imaged with both CT and NIR fluorescence modalities. By finely tuning the physical parameters such as gelation time and composition of iodinated oil (X-ray contrast agent) and indocyanine green (ICG, NIR fluorescence dye), we optimize the hydrogel for prolonged localization at the injected site without losing the dual-imaging capability. We validate the effectiveness of the developed injectable dual-imaging platform by performing image-guided resection of pulmonary nodules on tumor-bearing rabbits, which are preoperatively localized with the hydrogel. The injectable dual-imaging marker, therefore, can emerge as a powerful tool for surgical guidance.
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Colorantes Fluorescentes , Hidrogeles , Verde de Indocianina , Hidrogeles/química , Hidrogeles/administración & dosificación , Animales , Verde de Indocianina/administración & dosificación , Verde de Indocianina/química , Conejos , Colorantes Fluorescentes/química , Colorantes Fluorescentes/administración & dosificación , Cirugía Asistida por Computador , Imagen Óptica , Tomografía Computarizada por Rayos X , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/diagnóstico por imagen , Dextranos/química , Dextranos/administración & dosificación , Nódulos Pulmonares Múltiples/diagnóstico por imagen , Nódulos Pulmonares Múltiples/cirugía , Inyecciones , HumanosRESUMEN
The lymphatic system is active in several processes that regulate human diseases, among which cancer progression stands out. Thus, various drug delivery systems have been investigated to promote lymphatic drug targeting for cancer therapy; mainly, nanosized particles in the 10-150 nm range quickly achieve lymphatic vessels after an interstitial administration. Herein, a strategy to boost the lymphotropic delivery of Rose Bengal (RB), a hydrosoluble chemotherapeutic, is proposed, and it is based on the loading into Transfersomes (RBTF) and their intradermal deposition in vivo by microneedles. RBTF of 96.27 ± 13.96 nm (PDI = 0.29 ± 0.02) were prepared by a green reverse-phase evaporation technique, and they showed an RB encapsulation efficiency of 98.54 ± 0.09%. In vitro, RBTF remained physically stable under physiological conditions and avoided the release of RB. In vivo, intravenous injection of RBTF prolonged RB half-life of 50 min in healthy rats compared to RB intravenous injection; the RB half-life in rat body was further increased after intradermal injection reaching 24 h, regardless of the formulation used. Regarding lymphatic targeting, RBTF administered intravenously provided an RB accumulation in the lymph nodes of 12.3 ± 0.14 ng/mL after 2 h, whereas no RB accumulation was observed after RB intravenous injection. Intradermally administered RBTF resulted in the highest RB amount detected in lymph nodes after 2 h from the injection (84.2 ± 25.10 ng/mL), which was even visible to the naked eye based on the pink colouration of the drug. In the case of intradermally administered RB, RB in lymph node was detected only at 24 h (13.3 ± 1.41 ng/mL). In conclusion, RBTF proved an efficient carrier for RB delivery, enhancing its pharmacokinetics and promoting lymph-targeted delivery. Thus, RBTF represents a promising nanomedicine product for potentially facing the medical need for novel strategies for cancer therapy.
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Sistemas de Liberación de Medicamentos , Agujas , Rosa Bengala , Animales , Rosa Bengala/administración & dosificación , Rosa Bengala/farmacocinética , Inyecciones Intradérmicas , Masculino , Ratas Sprague-Dawley , Ganglios Linfáticos/metabolismo , Ratas , Microinyecciones , Colorantes Fluorescentes/administración & dosificación , Colorantes Fluorescentes/farmacocinéticaRESUMEN
BACKGROUND: This study analyzed the effectiveness and safety of ultra-low dose fluorescein sodium (FL)-guided malignant glioma resection and its potential to predict the pathological characteristics of glioma. METHODS: Sixty patients who underwent FL-guided glioma resection were randomly divided into test (1 mg/kg) and control (5 mg/kg) groups. A retrospective analysis included 30 patients with gliomas who did not undergo FL-guided surgery; these patients were included as a blank control group. Surgical outcomes, Karnofsky performance scores (KPS), and progression-free survival (PFS) at 6 months postoperatively were compared between the 3 groups. The sensitivity and specificity of FL and the relationship between the intensity of FL and Glial fibrillary acidic protein (GFAP) or Ki-67 expression were compared. RESULTS: The total tumor resection rates in the test, control, and blank control groups were 90% (27/30), 86.7% (26/30), and 60% (18/30), respectively. There were significant differences (P < 0.05) in the extent of resection, KPS, and PFS at 6 months after surgery between the test and control groups and the blank control group; however, no significant differences (P > 0.05) were observed between the test and control groups. The intensity of FL and the Ki67 positivity rate (P < 0.05) were directly proportional, but this relationship was not observed with GFAP. CONCLUSIONS: Ultra-low-dose FL-guided resection of malignant gliomas is safe and effective. The Ki67 positivity rate was directly proportional to the intensity of FL, indicating its potential to predict gliomas during pathological examination.
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Neoplasias Encefálicas , Fluoresceína , Glioma , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Encefálicas/cirugía , Fluoresceína/administración & dosificación , Colorantes Fluorescentes/administración & dosificación , Proteína Ácida Fibrilar de la Glía/metabolismo , Glioma/cirugía , Antígeno Ki-67/metabolismo , Antígeno Ki-67/análisis , Procedimientos Neuroquirúrgicos/métodos , Estudios Retrospectivos , Cirugía Asistida por Computador/métodos , Resultado del TratamientoRESUMEN
OBJECTIVE: FFA is a well-established investigation for the diagnosis of optic nerve abnormalities, requiring an intravenous cannula and extended imaging acquisition time. Cannulation can present a challenge in paediatric patients and whilst oral FFA has been used for decades, it has been limited by imaging technology and unconfirmed image acquisition timings. For years, we have used a modern ultra-widefield retinal camera, and established imaging time-points to demonstrate dynamic optic nerve head changes upon ingestion of fluorescein and collected a database of oFFA images for various presentations. METHODS: Using an established protocol, optic nerve colour images were obtained, followed by oral administration of fluorescein dye. The optic nerves are then imaged at established intervals. An interpretation of oFFA tutorial was delivered to consultant ophthalmologists and trainees. Subsequently, these groups were assessed using a series of fifteen cases with the sensitivity and specificity of the test determined. RESULTS: Our study presents a series of images and descriptions for common optic nerve abnormalities in paediatric populations. In the interpretation part of the study, overall sensitivity of 76.8% in the consultant group vs 63.3% in the combined consultant + trainees and specificity of 87.5% vs 68.4% in the combined group. CONCLUSIONS: This is the first study that describes characteristic features of several common, and serious, optic nerve abnormalities specifically for oFFA interpretation in a paediatric population. It also highlights the rapid accumulation of oFFA interpretation skills in non-specialist consultant and trainee ophthalmologists such as to obtain a high diagnostic accuracy with high sensitivity and specificity.
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Angiografía con Fluoresceína , Enfermedades del Nervio Óptico , Humanos , Niño , Angiografía con Fluoresceína/métodos , Masculino , Femenino , Preescolar , Enfermedades del Nervio Óptico/diagnóstico , Enfermedades del Nervio Óptico/diagnóstico por imagen , Fluoresceína/administración & dosificación , Administración Oral , Adolescente , Lactante , Disco Óptico/diagnóstico por imagen , Sensibilidad y Especificidad , Colorantes Fluorescentes/administración & dosificación , Nervio Óptico/diagnóstico por imagen , Nervio Óptico/anomalíasRESUMEN
BACKGROUND: Segmentectomy is a type of limited resection surgery indicated for patients with very early-stage lung cancer or compromised function because it can improve quality of life with minimal removal of normal tissue. For segmentectomy, an accurate detection of the tumor with simultaneous identification of the lung intersegment plane is critical. However, it is not easy to identify both during surgery. Here, the authors report dual-channel image-guided lung cancer surgery using renally clearable and physiochemically stable targeted fluorophores to visualize the tumor and intersegmental plane distinctly with different colors; cRGD-ZW800 (800 nm channel) targets tumors specifically, and ZW700 (700 nm channel) simultaneously helps discriminate segmental planes. METHODS: The near-infrared (NIR) fluorophores with 700 nm and with 800 nm channels were developed and evaluated the feasibility of dual-channel fluorescence imaging of lung tumors and intersegmental lines simultaneously in mouse, rabbit, and canine animal models. Expression levels of integrin αvß3, which is targeted by cRGD-ZW800-PEG, were retrospectively studied in the lung tissue of 61 patients who underwent lung cancer surgery. RESULTS: cRGD-ZW800-PEG has clinically useful optical properties and outperforms the FDA-approved NIR fluorophore indocyanine green and serum unstable cRGD-ZW800-1 in multiple animal models of lung cancer. Combined with the blood-pooling agent ZW700-1C, cRGD-ZW800-PEG permits dual-channel NIR fluorescence imaging for intraoperative identification of lung segment lines and tumor margins with different colors simultaneously and accurately. CONCLUSION: This dual-channel image-guided surgery enables complete tumor resection with adequate negative margins that can reduce the recurrence rate and increase the survival rate of lung cancer patients.
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Neoplasias Pulmonares , Márgenes de Escisión , Animales , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Ratones , Humanos , Perros , Conejos , Neumonectomía/métodos , Imagen Óptica/métodos , Femenino , Cirugía Asistida por Computador/métodos , Colorantes Fluorescentes/administración & dosificación , Masculino , Estudios Retrospectivos , Espectroscopía Infrarroja Corta/métodos , Persona de Mediana Edad , AncianoRESUMEN
BACKGROUND/AIM: Radiofrequency ablation (RFA) is used to treat primary and metastatic tumors in the liver. However, local recurrence after RFA is frequent and subsequent salvage hepatectomy is often ineffective due to difficulty in visualization of tumor margins. PATIENTS AND METHODS: In the present retrospective clinical trial, seven patients from the Department of General and Gastro-enterological Surgery, Showa University School of Medicine underwent salvage hepatectomy for recurrent hepatocellular carcinoma (HCC) (n=2), colorectal liver metastasis (n=4) and lung-carcinoid liver metastasis (n=1), after RFA, between 2011 and 2020. Tumors were labeled with indocyanine green (ICG) and resected under fluorescence guidance. Resected specimens were evaluated under fluorescence microscopy as well as by standard histopathological techniques. RESULTS: Pathological findings revealed negative tumor margins in all patients after fluorescence-guided surgery. Six of seven resected tumors had a fluorescent rim, including both HCC and liver metastasis. Fluorescence microscopy demonstrated that viable cancer tumor cells were located only on the inside of the fluorescent rim, and no malignant cells were detected within the fluorescent rim surrounding the tumor. Fluorescence microscopy showed that the tumor margin was secured if the fluorescence signal was completely resected. CONCLUSION: The present results demonstrate that ICG labeling of liver tumors recurring after RFA enabled complete resection under fluorescence guidance. The present study is the first clinical study to demonstrate that tumor types that generally cannot be completely resected with bright light are fully resectable under fluorescence guidance.
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Carcinoma Hepatocelular/cirugía , Colorantes Fluorescentes/administración & dosificación , Hepatectomía , Verde de Indocianina/administración & dosificación , Neoplasias Hepáticas/cirugía , Recurrencia Local de Neoplasia/cirugía , Ablación por Radiofrecuencia , Cirugía Asistida por Computador , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/patología , Femenino , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Masculino , Márgenes de Escisión , Microscopía Fluorescente , Recurrencia Local de Neoplasia/patología , Imagen Óptica , Reoperación , Estudios RetrospectivosRESUMEN
Corneal injuries can occur secondary to traumatic, chemical, inflammatory, metabolic, autoimmune, and iatrogenic causes. Ocular infection may frequently occur concurrent to corneal injury; however, antimicrobial agents are excluded from this present review. While practitioners may primarily rely on clinical examination techniques to assess these injuries, several pharmacological agents, such as fluorescein, lissamine green, and rose bengal, can be used to formulate a diagnosis and develop effective treatment strategies. Practitioners may choose from several analgesic medications to help with patient comfort without risking further injury or delaying ocular healing. Atropine, cyclopentolate, scopolamine, and homatropine are among the most frequently used medications for this purpose. Additional topical analgesic agents may be used judiciously to augment patient comfort to facilitate diagnosis. Steroidal anti-inflammatory agents are frequently used as part of the therapeutic regimen. A variety of commonly used agents, including prednisolone acetate, loteprednol, difluprednate, dexamethasone, fluorometholone, and methylprednisolone are discussed. While these medications are effective for controlling ocular inflammation, side effects, such as elevated intraocular pressure and cataract formation, must be monitored by clinicians. Non-steroidal medications, such as ketorolac, bromfenac, nepafenac, and diclofenac, are additionally used for their efficacy in controlling ocular inflammation without incurring side effects seen with steroids. However, these agents have their own respective side effects, warranting close monitoring by clinicians. Additionally, ophthalmologists routinely employ several agents in an off-label manner for supplementary control of inflammation and treatment of corneal injuries. Patients with corneal injuries not infrequently have significant ocular surface disease, either as a concurrent pathology or as an exacerbation of previously existing disease. Several agents used in the management of ocular surface disease have also been found to be useful as part of the therapeutic armamentarium for treatment of corneal injuries. For example, several antibiotics, such as doxycycline and macrolides, have been used for their anti-inflammatory effects on specific cytokines that are upregulated during acute injuries. There has been a recent wave of interest in amniotic membrane therapies (AMTs), including topical, cryopreserved and dehydrated variants. AMT is particularly effective in ocular injuries with violation of corneal surface integrity due to its ability to promote re-epithelialization of the corneal epithelium. Blood-based therapies, including autologous serum tears, plasma-enriched growth factor eyedrops and autologous blood drops, have additionally been explored in small case series for effectiveness in challenging and recalcitrant cases. Protection of the ocular surface is also a vital component in the treatment of corneal injuries. Temporary protective methods, such as bandage contact lenses and mechanical closure of the eyelids (tarsorrhaphy) can be particularly helpful in selective cases. Glue therapies, including biologic and non-biologic variants, can also be used in cases of severe injury and risk of corneal perforation. Finally, there are a variety of recently introduced and in-development agents that may be used as adjuvant therapies in challenging patient populations. Neurotrophic corneal disease may occur as a result of severe or chronic injury. In such cases, recombinant human nerve growth factor (cenegermin), topical insulin, and several other novel agents may be an alternate and effective option for clinicians to consider.
Asunto(s)
Corticoesteroides/uso terapéutico , Antibacterianos/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Lesiones de la Cornea/diagnóstico , Lesiones de la Cornea/tratamiento farmacológico , Adhesivos/uso terapéutico , Corticoesteroides/administración & dosificación , Corticoesteroides/efectos adversos , Amnios , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/efectos adversos , Córnea/efectos de los fármacos , Colorantes Fluorescentes/administración & dosificación , Humanos , Midriáticos/uso terapéutico , Gravedad del PacienteRESUMEN
Most protocols for lymphatic imaging of the lower limb conventionally inject tracer materials only into the interdigital space; however, recent studies indicate that there are four independent lymphatic vessel groups (anteromedial, anterolateral, posteromedial, and posterolateral) in the lower limb. Thus, three additional injection sites are needed for lymphatic imaging of the entire lower limb. We aimed to validate a multiple injection designed protocol and demonstrate its clinical benefits. Overall, 206 lower limbs undergoing indocyanine green fluorescent lymphography with the new injection protocol were registered retrospectively. To assess the influence of predictor variables on the degree of severity, multivariable logistic regression models were used with individual known risk factors. Using a generalized linear model, the area under the curve (AUC) of the conventional clinical model, comprising known severity risk factors, was compared with that of the modified model that included defects in the posterolateral and posteromedial groups. Multivariable logistic regression models showed a significant difference for the posteromedial and posterolateral groups. The AUC of the modified model was significantly improved compared to that of the conventional clinical model. Finding defects in the posteromedial and posterolateral groups is a significant criterion for judging lymphedema severity and introducing a new lymphedema severity classification.
Asunto(s)
Colorantes Fluorescentes/administración & dosificación , Verde de Indocianina/administración & dosificación , Extremidad Inferior/diagnóstico por imagen , Vasos Linfáticos/diagnóstico por imagen , Linfedema/diagnóstico por imagen , Linfografía , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inyecciones Subcutáneas , Linfedema/clasificación , Masculino , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
Purpose: After the lateral geniculate nucleus, the superior colliculus is the richest target of retinal projections in primates. Hubel et al. used tritium autoradiography to show that axon terminals emanating from one eye form irregular columns in the stratum griseum superficiale. Unlabeled gaps were thought to be filled by the other eye, but this assumption was never tested directly. Methods: Experiments were performed in two normal macaques. In monkey 1, [3H]proline was injected into the left eye and the pattern of radiolabeling was examined in serial cross-sections through the entire superior colliculus. In monkey 2, cholera toxin subunit B conjugated to Alexa 488 was injected into the right eye and cholera toxin subunit B - Alexa 594 was injected into the left eye. The two fluorescent labels were compared in a reconstruction of the superior colliculus prepared from serial sections. Results: In monkey 1, irregular columns of axon terminals were present in the superficial grey. The projection from the peripheral retina was stronger than the projection from the macula. In monkey 2, the two fluorescent Alexa tracers mainly interdigitated: a conspicuous gap in one label was usually filled by a clump of the other label. There was also partial laminar segregation of ocular inputs. In the far peripheral field representation, the contralateral eye's input generally terminated closer to the tectal surface. In the midperiphery the eyes switched, bringing the ipsilateral input nearer the surface. Conclusions: Direct retinal input to the macaque superior colliculus is segregated into alternating columns and strata, despite the fact that tectal cells respond robustly to stimulation of either eye.