Quantitative Phase Imaging as Sensitive Screening Method for Nanoparticle-Induced Cytotoxicity Assessment.

The assessment of nanoparticle cytotoxicity is challenging due to the lack of customized and standardized guidelines for nanoparticle testing. Nanoparticles, with their unique properties, can interfere with biochemical test methods, so multiple tests are required to fully assess their cellular effects. For a more reliable and comprehensive assessment, it is therefore imperative to include methods in nanoparticle testing routines that are not affected by particles and allow for the efficient integration of additional molecular techniques into the workflow. Digital holographic microscopy (DHM), an interferometric variant of quantitative phase imaging (QPI), has been demonstrated as a promising method for the label-free assessment of the cytotoxic potential of nanoparticles. Due to minimal interactions with the sample, DHM allows for further downstream analyses. In this study, we investigated the capabilities of DHM in a multimodal approach to assess cytotoxicity by directly comparing DHM-detected effects on the same cell population with two downstream biochemical assays. Therefore, the dry mass increase in RAW 264.7 macrophages and NIH-3T3 fibroblast populations measured by quantitative DHM phase contrast after incubation with poly(alkyl cyanoacrylate) nanoparticles for 24 h was compared to the cytotoxic control digitonin, and cell culture medium control. Viability was then determined using a metabolic activity assay (WST-8). Moreover, to determine cell death, supernatants were analyzed for the release of the enzyme lactate dehydrogenase (LDH assay). In a comparative analysis, in which the average half-maximal effective concentration (EC50) of the nanocarriers on the cells was determined, DHM was more sensitive to the effect of the nanoparticles on the used cell lines compared to the biochemical assays.

Durable 3D murine ex vivo retina glaucoma models for optical coherence tomography.

Durable and standardized phantoms with optical properties similar to native healthy and disease-like biological tissues are essential tools for the development, performance testing, calibration and comparison of label-free high-resolution optical coherence tomography (HR-OCT) systems. Available phantoms are based on artificial materials and reflect thus only partially ocular properties. To address this limitation, we have performed investigations on the establishment of durable tissue phantoms from ex vivo mouse retina for enhanced reproduction of in vivo structure and complexity. In a proof-of-concept study, we explored the establishment of durable 3D models from dissected mouse eyes that reproduce the properties of normal retina structures and tissue with glaucoma-like layer thickness alterations. We explored different sectioning and preparation procedures for embedding normal and N-methyl-D-aspartate (NMDA)-treated mouse retina in transparent gel matrices and epoxy resins, to generate durable three-dimensional tissue models. Sample quality and reproducibility were quantified by thickness determination of the generated layered structures utilizing computer-assisted segmentation of OCT B-scans that were acquired with a commercial HR-OCT system at a central wavelength of 905 nm and analyzed with custom build software. Our results show that the generated 3D models feature thin biological layers close to current OCT resolution limits and glaucoma-like tissue alterations that are suitable for reliable HR-OCT performance characterization. The comparison of data from resin-embedded tissue with native murine retina in gels demonstrates that by utilization of appropriate preparation protocols, highly stable samples with layered structures equivalent to native tissues can be fabricated. The experimental data demonstrate our concept as a promising approach toward the fabrication of durable biological 3D models suitable for high-resolution OCT system performance characterization supporting the development of optimized instruments for ophthalmology applications.

Single capture bright field and off-axis digital holographic microscopy: publisher's note.

This publisher's note contains corrections to Opt. Lett.48, 876 (2023)10.1364/OL.478674.

Single capture bright field and off-axis digital holographic microscopy.

We report on a single capture approach for simultaneous incoherent bright field (BF) and laser-based quantitative phase imaging (QPI). Common-path digital holographic microscopy (DHM) is implemented in parallel with BF imaging within the optical path of a commercial optical microscope to achieve spatially multiplexed recording of white light images and digital off-axis holograms, which are subsequently numerically demultiplexed. The performance of the proposed multimodal concept is firstly determined by investigations on microspheres. Then, the application for label-free dual-mode QPI and BF imaging of living pancreatic tumor cells is demonstrated.

Interlaboratory evaluation of a digital holographic microscopy-based assay for label-free in vitro cytotoxicity testing of polymeric nanocarriers.

State-of-the-art in vitro test systems for nanomaterial toxicity assessment are based on dyes and several staining steps which can be affected by nanomaterial interference. Digital holographic microscopy (DHM), an interferometry-based variant of quantitative phase imaging (QPI), facilitates reliable proliferation quantification of native cell populations and the extraction of morphological features in a fast and label- and interference-free manner by biophysical parameters. DHM therefore has been identified as versatile tool for cytotoxicity testing in biomedical nanotechnology. In a comparative study performed at two collaborating laboratories, we investigated the interlaboratory variability and performance of DHM in nanomaterial toxicity testing, utilizing complementary standard operating procedures (SOPs). Two identical custom-built off-axis DHM systems, developed for usage in biomedical laboratories, equipped with stage-top incubation chambers were applied at different locations in Europe. Temporal dry mass development, 12-h dry mass increments and morphology changes of A549 human lung epithelial cell populations upon incubation with two variants of poly(alkyl cyanoacrylate) (PACA) nanoparticles were observed in comparison to digitonin and cell culture medium controls. Digitonin as cytotoxicity control, as well as empty and cabazitaxel-loaded PACA nanocarriers, similarly impacted 12-h dry mass development and increments as well as morphology of A549 cells at both participating laboratories. The obtained DHM data reflected the cytotoxic potential of the tested nanomaterials and are in agreement with corresponding literature on biophysical and chemical assays. Our results confirm DHM as label-free cytotoxicity assay for polymeric nanocarriers as well as the repeatability and reproducibility of the technology. In summary, the evaluated DHM assay could be efficiently implemented at different locations and facilitates interlaboratory in vitro toxicity testing of nanoparticles with prospects for application in regulatory science.

Label-Free Digital Holographic Microscopy for In Vitro Cytotoxic Effect Quantification of Organic Nanoparticles.

Cytotoxicity quantification of nanoparticles is commonly performed by biochemical assays to evaluate their biocompatibility and safety. We explored quantitative phase imaging (QPI) with digital holographic microscopy (DHM) as a time-resolved in vitro assay to quantify effects caused by three different types of organic nanoparticles in development for medical use. Label-free proliferation quantification of native cell populations facilitates cytotoxicity testing in biomedical nanotechnology. Therefore, DHM quantitative phase images from measurements on nanomaterial and control agent incubated cells were acquired over 24 h, from which the temporal course of the cellular dry mass was calculated within the observed field of view. The impact of LipImage™ 815 lipidots® nanoparticles, as well as empty and cabazitaxel-loaded poly(alkyl cyanoacrylate) nanoparticles on the dry mass development of four different cell lines (RAW 264.7, NIH-3T3, NRK-52E, and RLE-6TN), was observed vs. digitonin as cytotoxicity control and cells in culture medium. The acquired QPI data were compared to a colorimetric cell viability assay (WST-8) to explore the use of the DHM assay with standard biochemical analysis methods downstream. Our results show that QPI with DHM is highly suitable to identify harmful or low-toxic nanomaterials. The presented DHM assay can be implemented with commercial microscopes. The capability for imaging of native cells and the compatibility with common 96-well plates allows high-throughput systems and future embedding into existing experimental routines for in vitro cytotoxicity assessment.

Uma proposta para parametrização de ações especializadas em saúde bucal / A proposal for parametrization of actions on secondary oral health care / A proposal for parametrization of actions on secondary oral health care

Introdução A definição de parâmetros assistenciais é de relevância para a execução de ações de saúde pública. Objetivo Descrever um percurso para elaboração de parâmetros de produção e de cobertura para endodontia e periodontia. Método Parâmetros de cobertura foram calculados a partir das necessidades normativas identificadas no levantamento epidemiológico de saúde bucal em Minas Gerais. Parâmetros de produção per capita foram calculados a partir das necessidades normativas, dos dados de produção do SIA/SUS e da capacidade instalada nos serviços. A análise foi desenvolvida no módulo Complex Samples do Programa SPSS. Resultados 6,2% (IC 95% 5,2%-7,3%) e 2,9% (IC 95% 2,2%-3,9%) dos indivíduos apresentavam, pelo menos, uma necessidade de tratamento endodôntico e periodontal, respectivamente. Em relação à produção, tanto a capacidade potencial de produção dos serviços especializados quanto a produção média registrada no SIA/SUS são muito inferiores às necessidades normativas globais da população. Conclusão A endodontia apresentou cobertura populacional e média de procedimentos maiores do que a periodontia. Os parâmetros de cobertura populacional podem ser utilizados para a organização dos serviços.

Background The definition of care parameters is relevant to the implementation of public health actions. Objective Describe a methodologic route for the elaboration of parameters on population coverage and production in endodontics and periodontics. Method Coverage parameters were calculated from the normative needs identified in the epidemiological survey of oral health in Minas Gerais. Production parameters were calculated based on normative requirements, SIA/SUS production data and installed capacity in the services. The analysis was developed in the Complex Samples module of the SPSS Program. Results 6.2% (95% CI 5.2%-7.3%) and 2.9% (CI 95% 2.2%-3.9%) needed endodontic and periodontal treatment, respectively. Both the potential production capacity of the specialized services and the average production recorded in the SIA/SUS were much lower than the overall normative needs of the population. Conclusion Endodontics presented a population coverage and average of procedures greater than that of periodontics. Population coverage parameters can be used to organize services.

Synchronization in pairs of rotating active biomotors.

Although synchronization is a well-known physical phenomenon, experimental studies of its emergence in living bacterial cells are still scarce. The difficulty in generating a controlled scenario to detect synchronization has limited the experimental outcomes so far. We present a realization based on holographic optical tweezers in which adhered pairs of self-propelled bacteria rotate in a plane. The separation distance between the bacteria determines the strength of the hydrodynamic coupling. Despite the noisy environment and autonomous dynamics of the living bacteria, we find evidence of phase locking and frequency entrainment in their rotation. The observation of higher order frequency synchronization is also discussed.

Massive ordering and alignment of cylindrical micro-objects by photovoltaic optoelectronic tweezers.

Optical tools for manipulation and trapping of micro- and nano-objects are a fundamental issue for many applications in nano- and biotechnology. This work reports on the use of one such method, known as photovoltaic optoelectronics tweezers, to orientate and organize cylindrical microcrystals, specifically elongated zeolite L, on the surface of Fe-doped LiNbO3 crystal plates. Patterns of aligned zeolites have been achieved through the forces and torques generated by the bulk photovoltaic effect. The alignment patterns with zeolites parallel or perpendicular to the substrate surface are highly dependent on the features of light distribution and crystal configuration. Moreover, dielectrophoretic chains of zeolites with lengths up to 100 µm have often been observed. The experimental results of zeolite trapping and alignment have been discussed and compared together with theoretical simulations of the evanescent photovoltaic electric field and the dielectrophoretic potential. They demonstrate the remarkable capabilities of the optoelectronic photovoltaic method to orientate and pattern anisotropic microcrystals. The combined action of patterning and alignment offers a unique tool to prepare functional nanostructures with potential applications in a variety of fields such as nonlinear optics or plasmonics.

Biolens behavior of RBCs under optically-induced mechanical stress.

In this work, the optical behavior of Red Blood Cells (RBCs) under an optically-induced mechanical stress was studied. Exploiting the new findings concerning the optical lens-like behavior of RBCs, the variations of the wavefront refracted by optically-deformed RBCs were further investigated. Experimental analysis have been performed through the combination of digital holography and numerical analysis based on Zernike polynomials, while the biological lens is deformed under the action of multiple dynamic optical tweezers. Detailed wavefront analysis provides comprehensive information about the aberrations induced by the applied mechanical stress. By this approach it was shown that the optical properties of RBCs in their discocyte form can be affected in a different way depending on the geometry of the deformation. In analogy to classical optical testing procedures, optical parameters can be correlated to a particular mechanical deformation. This could open new routes for analyzing cell elasticity by examining optical parameters instead of direct but with low resolution strain analysis, thanks to the high sensitivity of the interferometric tool. Future application of this approach could lead to early detection and diagnosis of blood diseases through a single-step wavefront analysis for evaluating different cells elasticity. © 2017 International Society for Advancement of Cytometry.

Spatiotemporally Resolved Tracking of Bacterial Responses to ROS-Mediated Damage at the Single-Cell Level with Quantitative Functional Microscopy.

Herein we report on the implementation of photofunctional microparticles in combination with optical tweezers for the investigation of bacterial responses to oxidative stress by means of quantitative functional microscopy. A combination of a strongly hydrophobic axially substituted Si(IV) phthalocyanine adsorbed onto silica microparticles was developed, and the structural and photophysical characterization was carried out. The microparticles are able to produce reactive oxygen species under the fluorescence microscope upon irradiation with red light, and the behavior of individual bacteria can be consequently investigated in situ and in real time at the single cell level. For this purpose, a methodology was introduced to monitor phototriggered changes with spatiotemporal resolution. The defined distance between the photoactive particles and individual bacteria can be fixed under the microscope before the photosensitization process is started, and the photoinduced damage can be monitored by tracing the time-dependent fluorescence turn-on of a suitable marker. The results showed a distance-dependent photoinduced death time, defined as the onset of the incorporation of propidium iodide. Our methodology constitutes a new tool for the in vitro design and evaluation of photosensitizers for the treatment of cancer and infectious diseases with the aid of functional optical microscopy, as it enables a quantitative response evaluation of living systems toward oxidative stress. More generally, it provides a way to understand the response of an ensemble of living entities to reactive oxygen species by analyzing the behavior of a set of individual organisms.

Optical assembly of bio-hybrid micro-robots.

The combination of micro synthetic structures with bacterial flagella motors represents an actual trend for the construction of self-propelled micro-robots. The development of methods for fabrication of these bacteria-based robots is a first crucial step towards the realization of functional miniature and autonomous moving robots. We present a novel scheme based on optical trapping to fabricate living micro-robots. By using holographic optical tweezers that allow three-dimensional manipulation in real time, we are able to arrange the building blocks that constitute the micro-robot in a defined way. We demonstrate exemplarily that our method enables the controlled assembly of living micro-robots consisting of a rod-shaped prokaryotic bacterium and a single elongated zeolite L crystal, which are used as model of the biological and abiotic components, respectively. We present different proof-of-principle approaches for the site-selective attachment of the bacteria on the particle surface. The propulsion of the optically assembled micro-robot demonstrates the potential of the proposed method as a powerful strategy for the fabrication of bio-hybrid micro-robots.

Parametrização de procedimentos e de cobertura nas áreas de endodontia, periodontia e exodontia para as populações adolescente, adulta e idosa de Minas Gerais / Parameterization of procedures and coverage in endodontics, periodontics and surgery in adolescents, adults and elderly people in Minas Gerais, Brazil

A melhoria nas condições econômicas e sociais alcançadas nestes últimos anos no Brasil e a implantação do Programa Brasil Sorridente trouxeram um avanço significativo das condições de saúde bucal em todas as faixas etárias da população brasileira. Entretanto os agravos em saúde bucal continuam com prevalência acima do preconizado pela Organização Mundial da Saúde. Para um constante avanço da saúde bucal é necessário o conhecimento da realidade epidemiológica localmente para subsidiar o planejamento e melhorar a vigilância em saúde. O emprego de indicadores e parâmetros é fundamental para alcançarmos as metas propostas, o aperfeiçoamento do processo de gestão e consequentemente a melhoria na prestação dos serviços em saúde bucal. O processo de pactuação de metas e os parâmetros propostos são frágeis e de pouca confiabilidade. Necessitando de serem revistos e redimensionados, tanto na atenção básica quanto na atenção especializada. Este estudo propõe o redimensionamento dos parâmetros de cobertura e produção nas áreas de endodontia, periodontia e exodontia nas faixas etárias de 15 a 19, 35 a 44 e 65 a 74 anos da população do Estado de Minas Gerais. Trata-se de um estudo exploratório, quantitativo e descritivo. Os parâmetros foram calculados tendo como base as necessidades da população encontradas no levantamento epidemiológico SB-Minas Gerais e os dados de produtividade encontrados no SIA/SUS, entre os anos de 2010 e 2013. Este estudo identificou que os parâmetros de cobertura e produtividade mais altos foram identificados para as exodontias, exceto entre os adolescentes para os quais os parâmetros de endodontia obtiveram valores mais altos. Menores valores dos parâmetros foram identificados entre idosos nas áreas de endodontia e exodontias. Portanto o presente estudo vem reafirmar a importância de se ter como referência, dados epidemiológicos de origem local, como forma de se conferir maior adequação a este processo de parametrização

The improvement in economic and social conditions achieved in recent years in Brazil and the Smiling Brazil Program deployment, there was a significant advance oral health conditions in all age groups of the population. However the aggravations in oral health continue with high prevalence and with targets above the recommended by the World Health Organization. For a constant advancement of oral health knowledge is required of the epidemiological reality locally to support the planning and improve health surveillance. The use of indicators and parameters is essential to achieve the proposed goals, to improve the management process and consequently the improvement in the provision of oral health services. The process of determining goals and parameters proposed are fragile and unreliable. Need to be reviewed and resized, both in the basic attention and specialized attention. This study proposes the resizing of the parameters and production in the fields of Endodontics, Periodontics and dental extraction in the age group of 15 to 19, 35 to 44 and 65 to 74 years the population of the State of Minas Gerais. It is a exploratory study, quantitative and descriptive. The parameters were calculated based on the needs of production and coverage found in the epidemiological survey SB-Minas Gerais and productivity data found in the SIA/SUS, between 2010 and 2013. This study identified that the parameters of coverage and higher productivity were identified for the dental extractions, except among teenagers for which the parameters of Endodontics have obtained higher values. Smaller values of the parameters were identified among the elderly in the areas of Endodontics and dental extractions. Therefore this study comes to reaffirm the importance of having as a reference, epidemiological data of local origin, as a way to confer greater fitness for this parameterization process

Towards 3D modelling and imaging of infection scenarios at the single cell level using holographic optical tweezers and digital holographic microscopy.

The analysis of dynamic interactions of microorganisms with a host cell is of utmost importance for understanding infection processes. We present a biophotonic holographic workstation that allows optical manipulation of bacteria by holographic optical tweezers and simultaneously monitoring of dynamic processes with quantitative multi-focus phase imaging based on self-interference digital holographic microscopy. Our results show that several bacterial cells, even with non-spherical shape, can be aligned precisely on the surface of living host cells and localized reproducibly in three dimensions. In this way a new label-free multipurpose device for modelling and quantitative analysis of infection scenarios at the single cell level is provided.

Three-dimensional exploration and mechano-biophysical analysis of the inner structure of living cells.

A novel mechanobiological method is presented to explore qualitatively and quantitatively the inside of living biological cells in three dimensions, paving the way to sense intracellular changes during dynamic cellular processes. For this purpose, holographic optical tweezers, which allow the versatile manipulation of nanoscopic and microscopic particles by means of tailored light fields, are combined with self-interference digital holographic microscopy. This biophotonic holographic workstation enables non-contact, minimally invasive, flexible, high-precision optical manipulation and accurate 3D tracking of probe particles that are incorporated by phagocytosis in cells, while simultaneously quantitatively phase imaging the cell morphology. In a first model experiment, internalized polystyrene microspheres with 1 µm diameter are three-dimensionally moved and tracked in order to quantify distances within the intracellular volume with submicrometer accuracy. Results from investigations on cell swelling provoked by osmotic stimulation demonstrate the homogeneous stretching of the cytoskeleton network, and thus that the proposed method provides a new way for the quantitative 3D analysis of the dynamic intracellular morphology.

[Contribution of computed tomography in patients with lung metastases of differentiated thyroid carcinoma not apparent on plain radiography who were treated with radioiodine]. / Contribuição da tomografia computadorizada em pacientes com metástases pulmonares de carcinoma diferenciado de tireóide não-aparentes na radiografia e tratados com radioiodo.

Computed tomography (CT or CAT Scan) of the chest is more sensitive than radiography in the detection of lung metastases of differentiated thyroid cancer (DTC), but little information is available regarding the aggregated value of this method. The present study evaluated the response of patients with lung metastases of DTC not apparent on radiography to treatment with 131I and the value of CT in these cases. Twenty-five patients with lung metastases not apparent on radiography, who initially received 100-200 mCi I151, were evaluated and those presenting pulmonary uptake on post-therapy WBS were submitted to a new treatment after 6 to 12 months, and so on. The chance of detection of pulmonary uptake on post-therapy WBS did not differ between patients with negative and positive CT (100% versus 91.5%). Mean serum Tg levels were higher in patients with positive CT (108 ng/ml versus 52 ng/ml). Negative post-therapy WBS was achieved in 82% of patients with positive CT and in 92.3% with negative CT and the cumulative I131 activity necessary to achieve this outcome did not differ between the two groups (mean=300 mCi). Stimulated Tg was undetectable in 47% of patients with negative CT at the end of treatment, but in none of the patients whose CT continued to be positive. In patients with elevated Tg, the CT result apparently did not change the indication of therapy or the I131 activity to be administered. In cases with lung metastases, the persistence of micronodules on CT was associated with the persistence of detectable Tg in patients presenting negative post-therapy WBS.

Contribuição da tomografia computadorizada em pacientes com metástases pulmonares de carcinoma diferenciado de tireóide não-aparentes na radiografia e tratados com radioiodo / Contribution of computed tomography in patients with lung metastases of differentiated thyroid carcinoma not apparent on plain radiography who were treated with radioiodine

A tomografia computadorizada (TC) de tórax é mais sensível que a radiografia na detecção de metástases pulmonares do carcinoma diferenciado de tireóide (CDT), sendo importante conhecer melhor o valor agregado desse método. Este estudo avaliou a resposta ao tratamento com 131I em pacientes com metástases pulmonares de CDTs não-aparentes na radiografia e o valor da TC nesses casos. Foram avaliados 25 pacientes com metástases pulmonares não-aparentes na radiografia, que receberam inicialmente 100 a 200 mCi de 131I. Naqueles com pesquisa de corpo inteiro (PCI) pós-dose com captação pulmonar, um novo tratamento era realizado após seis a 12 meses, e assim sucessivamente. A chance do encontro de captação pulmonar na PCI pós-dose não foi diferente em pacientes com TC negativa ou positiva (100 por cento versus 91,5 por cento). Os valores médios de tireoglobulina (Tg) sérica foram maiores naqueles com TC positiva (108 ng/mL versus 52 ng/mL). PCI pós-dose negativa foi alcançada em 82 por cento dos pacientes com TC positiva e em 92,3 por cento com TC negativa, e a atividade acumulada de 131I para alcançar essa resposta não foi diferente nos dois grupos (em média, 300 mCi). Quarenta e sete por cento dos pacientes com TC negativa ao final do tratamento apresentaram Tg estimulada indetectável, mas nenhum daqueles que permaneceu com TC positiva apresentou-a. Em pacientes com Tg elevada, o resultado da TC aparentemente não altera a indicação da terapia e a atividade de 131I a ser administrada. Nos casos com metástases pulmonares, a permanência de micronódulos na TC nos pacientes com PCI pós-dose negativa após o tratamento foi associada à persistência de Tg detectável.

Computed tomography (CT or CAT Scan) of the chest is more sensitive than radiography in the detection of lung metastases of differentiated thyroid cancer (DTC), but little information is available regarding the aggregated value of this method. The present study evaluated the response of patients with lung metastases of DTC not apparent on radiography to treatment with 131I and the value of CT in these cases. Twenty-five patients with lung metastases not apparent on radiography, who initially received 100-200 mCi I151, were evaluated and those presenting pulmonary uptake on post-therapy WBS were submitted to a new treatment after 6 to 12 months, and so on. The chance of detection of pulmonary uptake on post-therapy WBS did not differ between patients with negative and positive CT (100 percent versus 91.5 percent). Mean serum Tg levels were higher in patients with positive CT (108 ng/ml versus 52 ng/ml). Negative post-therapy WBS was achieved in 82 percent of patients with positive CT and in 92.3 percent with negative CT and the cumulative I131 activity necessary to achieve this outcome did not differ between the two groups (mean = 300 mCi). Stimulated Tg was undetectable in 47 percent of patients with negative CT at the end of treatment, but in none of the patients whose CT continued to be positive. In patients with elevated Tg, the CT result apparently did not change the indication of therapy or the I131 activity to be administered. In cases with lung metastases, the persistence of micronodules on CT was associated with the persistence of detectable Tg in patients presenting negative post-therapy WBS.

Is adjuvant therapy useful in patients with papillary carcinoma smaller than 2 cm?

To evaluate tumor recurrence after total thyroidectomy in patients with single papillary carcinoma with size 0.5 mIU/L in >or=50% of the measurements in all patients. Complete remission (stimulated thyroglobulin (Tg) 0.05). Six patients who still had stimulated Tg > 1 ng/mL (<5 ng/mL) showed a >50% decrease in comparison with Tg measured 12-24 months earlier. In conclusion, we suggest a more conservative approach with respect to central-compartment neck dissection, postoperative (131)I, and suppressive therapy in patients with small tumors restricted to the thyroid.

Management of low-risk patients with thyroid carcinoma and detectable thyroglobulin on T4 after thyroidectomy and ablation with iodine-131.

OBJECTIVE: To evaluate the positive predictive value of detectable Tg during T4 therapy (Tg on T4) in patients with thyroid cancer after total thyroidectomy and remnant ablation, discussing the work-up in this situation and the empirical indication of 131I. PATIENTS AND METHODS: Initially, 234 low-risk patients [tumor < 5cm, completely resected, no extensive extrathyroid invasion (pT4)] submitted to total thyroidectomy and ablation with 131I (3.7-5.5 GBq) who presented no ectopic uptake on RxWBS were studied. Of these, 23 patients with detectable Tg on T4 (> 1ng/ml) during the first year after initial therapy were selected. RESULTS: Metastases were detected by neck US in 7 patients, by chest CT in 2 and by US and CT in 3. Four of five patients with lung metastases upon CT had a positive RxWBS. Eleven patients with negative US and CT received a new 131I dose (without DxWBS), and RxWBS showed ectopic uptake in 3 patients. Among the patients with negative RxWBS, 7 remained free of apparent disease and Tg was declining (5 with undetectable Tg on T4 at the end of the study). One patient presented an increase in Tg and FDG-PET was positive for lymph node and bone metastases. CONCLUSIONS: All patients with Tg on T4 > 5ng/ml presented apparent disease. In these cases, even when US and CT are negative, the administration of a therapeutic dose of 131I (without DxWBS) and FDG-PET are recommended. Among patients with detectable Tg on T4