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OBJECTIVE: To evaluate the benefits of probe-based near-infrared autofluorescence (NIRAF) parathyroid identification during parathyroidectomy. BACKGROUND: Intraoperative parathyroid gland identification during parathyroidectomy can be challenging, while additionally requiring costly frozen sections. Earlier studies have established NIRAF detection as a reliable intraoperative adjunct for parathyroid identification. METHODS: Patients undergoing parathyroidectomy for primary hyperparathyroidism were prospectively enrolled by a senior surgeon (>20 years experience) and a junior surgeon (<5 years experience), while being randomly allocated to the probe-based NIRAF or control group. Data collected included procedure type, number of parathyroids identified with high confidence by the surgeon and the resident, number of frozen sections performed, parathyroidectomy duration, and number of patients with persistent disease at the first postoperative visit. RESULTS: One hundred sixty patients were randomly enrolled under both surgeons to the probe group (n=80) versus control (n=80). In the probe group, parathyroid identification rate of the senior surgeon improved significantly from 3.2 to 3.6 parathyroids per patient ( P <0.001), while that of the junior surgeon also rose significantly from 2.2 to 2.5 parathyroids per patient ( P =0.001). Parathyroid identification was even more prominent for residents increasing significantly from 0.9 to 2.9 parathyroids per patient ( P <0.001). Furthermore, there was a significant reduction in frozen sections utilized in the probe group versus control (17 vs 47, P =0.005). CONCLUSION: Probe-based NIRAF detection can be a valuable intraoperative adjunct and educational tool for improving confidence in parathyroid gland identification, while potentially reducing the number of frozen sections required.
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Glándulas Paratiroides , Paratiroidectomía , Humanos , Glándulas Paratiroides/diagnóstico por imagen , Glándulas Paratiroides/cirugía , Paratiroidectomía/métodos , Microcirugia , Hormona ParatiroideaRESUMEN
BACKGROUND: Accurate parathyroid gland (PG) identification is a critical yet challenging component of cervical endocrine procedures. PGs possess strong near-infrared autofluorescence (NIRAF) compared with other tissues in the neck. This property has been harnessed by image- and probe-based near-infrared fluorescence detection systems, which have gained increasing popularity in clinical use for their ability to accurately aid in PG identification in a rapid, noninvasive, and cost-effective manner. All NIRAF technologies, however, cannot differentiate viable from devascularized PGs without the use of contrast enhancement. Here, we aim to provide an overview of the rapid evolution of these technologies and update the surgery community on the most recent advancements in the field. METHODS: A PubMed literature review was performed using the key terms "parathyroid," "near-infrared," and "fluorescence." Recommendations regarding the use of these technologies in clinical practice were developed on the basis of the reviewed literature and in conjunction with expert surgeons' opinions. RESULTS: The use of near-infrared fluorescence detection can be broadly categorized as (1) using parathyroid NIRAF to identify both healthy and diseased PGs, and (2) using contrast-enhanced (i.e., indocyanine green) near-infrared fluorescence to evaluate PG perfusion and viability. Each of these approaches possess unique advantages and disadvantages, and clinical trials are ongoing to better define their utility. CONCLUSIONS: Near-infrared fluorescence detection offers the opportunity to improve our collective ability to identify and preserve PGs intraoperatively. While additional work is needed to propel this technology further, we hope this review will be valuable to the practicing surgeon.
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Glándulas Paratiroides , Glándula Tiroides , Humanos , Glándulas Paratiroides/diagnóstico por imagen , Glándulas Paratiroides/cirugía , Glándula Tiroides/cirugía , Tiroidectomía/métodos , Cuello/cirugía , Paratiroidectomía/métodos , Imagen Óptica/métodosRESUMEN
BACKGROUND: During adrenalectomy, surgeons have traditionally relied on their subjective visual skills to distinguish adrenal glands (AGs) from retroperitoneal fat and surrounding structures, while ultrasound and exogenous contrast agents have been employed for intraoperative AG visualization, all of which have their limitations. We present a novel label-free approach that uses near-infrared autofluorescence (NIRAF) detection, which demonstrates potential for enhanced intraoperative AG visualization and efficient tumor resection during adrenalectomies. METHODS: Patients undergoing adrenalectomy or nephrectomy were enrolled for this feasibility study. NIRAF emitted beyond 800 nm was detected in vivo from AGs and surrounding tissues during open adrenalectomies or nephrectomies. NIRAF was also measured ex vivo in excised AGs following robotic adrenalectomies. NIRAF images of tissues were captured using near-infrared (NIR) camera systems, whereas NIRAF intensities were recorded concurrently using fiber-optic probe-based NIR devices. Normalized NIRAF intensities (expressed as mean ± standard error) were analyzed and compared. RESULTS: Among the 55 enrolled patients, NIRAF intensity was elevated significantly for AGs versus retroperitoneal fat and other structures. NIR images of AGs also revealed a distinct demarcation of NIRAF between adrenal cortex and other periadrenal structures. NIRAF intensity in AGs was decreased markedly in malignant adrenal tumors, while benign adrenal cortical tumors and healthy adrenal cortex exhibited the strongest NIRAF levels. CONCLUSIONS: Our preliminary findings indicate that NIRAF detection could be a promising label-free technology to enhance intraoperative AG visualization and holds immense potential for effective tumor demarcation during cortical-sparing adrenalectomies or adrenal-conserving surgeries.
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Neoplasias de las Glándulas Suprarrenales , Glándulas Suprarrenales , Humanos , Glándulas Suprarrenales/diagnóstico por imagen , Glándulas Suprarrenales/cirugía , Paratiroidectomía/métodos , Adrenalectomía/métodos , Tiroidectomía/métodos , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Neoplasias de las Glándulas Suprarrenales/cirugíaRESUMEN
BACKGROUND: Biochemical cervical change during labor is not well understood, in part, because of a dearth of technologies capable of safely probing the pregnant cervix in vivo. The need for such a technology is 2-fold: (1) to gain a mechanistic understanding of the cervical ripening and dilation process and (2) to provide an objective method for evaluating the cervical state to guide clinical decision-making. Raman spectroscopy demonstrates the potential to meet this need, as it is a noninvasive optical technique that can sensitively detect alterations in tissue components, such as extracellular matrix proteins, lipids, nucleic acids, and blood, which have been previously established to change during the cervical remodeling process. OBJECTIVE: We sought to demonstrate that Raman spectroscopy can longitudinally monitor biochemical changes in the laboring cervix to identify spectral markers of impending parturition. STUDY DESIGN: Overall, 30 pregnant participants undergoing either spontaneous or induced labor were recruited. The Raman spectra were acquired in vivo at 4-hour intervals throughout labor until rupture of membranes using a Raman system with a fiber-optic probe. Linear mixed-effects models were used to determine significant (P<.05) changes in peak intensities or peak ratios as a function of time to delivery in the study population. A nonnegative least-squares biochemical model was used to extract the changing contributions of specific molecule classes over time. RESULTS: We detected multiple biochemical changes during labor, including (1) significant decreases in Raman spectral features associated with collagen and other extracellular matrix proteins (P=.0054) attributed to collagen dispersion, (2) an increase in spectral features associated with blood (P=.0372), and (3) an increase in features indicative of lipid-based molecules (P=.0273). The nonnegative least-squares model revealed a decrease in collagen contribution with time to delivery, an increase in blood contribution, and a change in lipid contribution. CONCLUSION: Our findings have demonstrated that in vivo Raman spectroscopy is sensitive to multiple biochemical remodeling changes in the cervix during labor. Furthermore, in vivo Raman spectroscopy may be a valuable noninvasive tool for objectively evaluating the cervix to potentially guide clinical management of labor.
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Cuello del Útero , Espectrometría Raman , Maduración Cervical , Cuello del Útero/diagnóstico por imagen , Colágeno/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Femenino , Humanos , Lípidos , Embarazo , Espectrometría Raman/métodosRESUMEN
BACKGROUND AND OBJECTIVE: The Food and Drug Administration has cleared a probe-based near-infrared autofluorescence (NIRAF) detection system called PTeye™ as an adjunct tool for label-free intraoperative parathyroid gland (PG) identification. Since PTeye™ has been investigated only in a "blinded" manner to date, this study describes the preliminary impressions of PTeye™ when used by surgeons without being blinded to the device output. METHODS: Patients undergoing thyroid and parathyroid procedures were prospectively recruited. Target tissues were intraoperatively assessed with PTeye™. The surgeon's confidence in PG identification was recorded concomitantly with NIRAF parameters that were output in real-time from PTeye™. RESULTS: A retrospective review of prospectively collected data on 83 patients was performed. PTeye™ was used for interrogating 336 target tissues in 46 parathyroid and 37 thyroid procedures. PTeye™ yielded an overall accuracy of 94.3% with a positive predictive value of 93.0% and a negative predictive value of 100%. An increase in confidence for intraoperative PG identification with PTeye™ was observed by all three participating high-volume surgeons, irrespective of their level of accrued surgical experience. CONCLUSIONS: Probe-based NIRAF detection with PTeye™ can be a valuable adjunct device to intraoperatively identify PGs for surgeons of varied training and experience.
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Glándulas Paratiroides/diagnóstico por imagen , Glándulas Paratiroides/cirugía , Paratiroidectomía/métodos , Espectroscopía Infrarroja Corta/métodos , Tiroidectomía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Cuidados Intraoperatorios/métodos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Espectroscopía Infrarroja Corta/instrumentación , Adulto JovenRESUMEN
OBJECTIVE: With the recent approval of 2 NIRAF-based devices for label-free identification of PG by the Food and Drug Administration, it becomes crucial to educate the surgical community on the realistic scope of this emerging technology. Here, we have compiled a review of studies that utilize NIRAF and present a critical appraisal of this technique for intraoperative PG detection. BACKGROUND: Failure to visualize PGs could lead to accidental damage/excision of healthy PGs or inability to localize diseased PGs, resulting in postsurgical complications. The discovery that PGs have NIRAF led to new avenues for intraoperatively identifying PGs with high accuracy in real-time. METHODS: Using the following key terms: "parathyroid, near infrared, autofluorescence" in various search engines such as PubMed and Google Scholar, we identified various publications relevant to this review of NIRAF as a technique for PG identification. Articles were excluded if they focused solely on contrast agents, served as commentaries/overviews on NIRAF or were not written in English. RESULTS: To date, studies have investigated the potential of NIRAF detection for (i) identifying PG tissues intraoperatively, (ii) locating PGs before or after dissection, (iii) distinguishing healthy from diseased PGs, and (iv) minimizing postoperative hypocalcemia after total thyroidectomy. CONCLUSIONS: Because NIRAF-based identification of PG is noninvasive and label-free, the popularity of this approach has considerably surged. As the present limitations of various technologies capable of NIRAF detection are identified, we anticipate that newer device iterations will continue to be developed enhancing the current merits of these modalities to aid surgeons in identifying and preserving PGs. However, more concrete and long-term outcome studies with these modalities are essential to determine the impact of this technique on patient outcome and actual cost-benefits.
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Cuidados Intraoperatorios/métodos , Imagen Óptica , Glándulas Paratiroides/diagnóstico por imagen , Paratiroidectomía , Diseño de Equipo , Humanos , Imagen Óptica/instrumentación , Imagen Óptica/métodos , Paratiroidectomía/métodos , Espectroscopía Infrarroja Corta/instrumentaciónRESUMEN
Esophageal diseases result in significant mortality, morbidity, and health care costs worldwide. Current approaches to detect and monitor esophageal diseases have severe limitations. Advanced imaging technologies are being developed to complement current approaches to improve diagnostic, therapeutic and surveillance protocols in order to advance the field. Raman spectroscopy-based technologies hold promise to increase the sensitivity for detection of diseased and high-risk lesions in vitro and in vivo in real time. This technique allows for the investigation of microstructural changes and also facilitates the discovery of disease-specific biochemical alterations with the potential to provide novel insights into the pathobiology of these conditions. Raman spectroscopy has been increasingly applied in precancerous and cancerous esophageal conditions. However, its application in benign esophageal diseases is still in the early stages. Continuing its application in cancerous and precancerous conditions and expanding its use to benign esophageal disorders could lay a foundation for integration of this technology in clinical practice and diagnostic paradigms and development of an accurate and cost-effective tool for use in a clinical setting. Furthermore, Raman spectroscopy can also be used as an innovative technique to advance our understanding of the biochemical transformations associated with esophageal diseases and answer a myriad of fundamental questions in the field. In this review, we described the principles of Raman spectroscopy and instrumentation while providing an overview of current applications, challenges, and future directions in the context of esophageal diseases with an emphasis on its clinical translational application.
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Enfermedades del Esófago/diagnóstico , Espectrometría Raman/métodos , Humanos , Espectrometría Raman/instrumentaciónRESUMEN
BACKGROUND: The cervix must undergo significant biochemical remodeling to allow for successful parturition. This process is not fully understood, especially in instances of spontaneous preterm birth. In vivo Raman spectroscopy is an optical technique that can be used to investigate the biochemical composition of tissue longitudinally and noninvasively in human beings, and has been utilized to measure physiology and disease states in a variety of medical applications. OBJECTIVE: The purpose of this study is to measure in vivo Raman spectra of the cervix throughout pregnancy in women, and to identify biochemical markers that change with the preparation for delivery and postpartum repair. STUDY DESIGN: In all, 68 healthy pregnant women were recruited. Raman spectra were measured from the cervix of each patient monthly in the first and second trimesters, weekly in the third trimester, and at the 6-week postpartum visit. Raman spectra were measured using an in vivo Raman system with an optical fiber probe to excite the tissue with 785 nm light. A spectral model was developed to highlight spectral regions that undergo the most changes throughout pregnancy, which were subsequently used for identifying Raman peaks for further analysis. These peaks were analyzed longitudinally to determine if they underwent significant changes over the course of pregnancy (P < .05). Finally, 6 individual components that comprise key biochemical constituents of the human cervix were measured to extract their contributions in spectral changes throughout pregnancy using a linear combination method. Patient factors including body mass index and parity were included as variables in these analyses. RESULTS: Raman peaks indicative of extracellular matrix proteins (1248 and 1254 cm-1) significantly decreased (P < .05), while peaks corresponding to blood (1233 and 1563 cm-1) significantly increased (P < .0005) in a linear manner throughout pregnancy. In the postpartum cervix, significant increases in peaks corresponding to actin (1003, 1339, and 1657 cm-1) and cholesterol (1447 cm-1) were observed when compared to late gestation, while signatures from blood significantly decreased. Postpartum actin signals were significantly higher than early pregnancy, whereas extracellular matrix proteins and water signals were significantly lower than early weeks of gestation. Parity had a significant effect on blood and extracellular matrix protein signals, with nulliparous patients having significant increases in blood signals throughout pregnancy, and higher extracellular matrix protein signals in early pregnancy compared to patients with prior pregnancies. Body mass index significantly affected actin signal contribution, with low body mass index patients showing decreasing actin contribution throughout pregnancy and high body mass index patients demonstrating increasing actin signals. CONCLUSION: Raman spectroscopy was successfully used to biochemically monitor cervical remodeling in pregnant women during prenatal visits. This foundational study has demonstrated sensitivity to known biochemical dynamics that occur during cervical remodeling, and identified patient variables that have significant effects on Raman spectra throughout pregnancy. Raman spectroscopy has the potential to improve our understanding of cervical maturation, and be used as a noninvasive preterm birth risk assessment tool to reduce the incidence, morbidity, and mortality caused by preterm birth.
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Cuello del Útero/fisiología , Parto/fisiología , Primer Trimestre del Embarazo/fisiología , Segundo Trimestre del Embarazo/fisiología , Tercer Trimestre del Embarazo/fisiología , Espectrometría Raman , Adulto , Femenino , Voluntarios Sanos , Humanos , Periodo Posparto , EmbarazoRESUMEN
INTRODUCTION: Biochemical alterations in the esophagus of patients with eosinophilic esophagitis (EoE) are poorly understood. We used Raman spectroscopy through a pediatric endoscope to identify key Raman features reflective of the esophageal biochemical composition to differentiate between children with EoE from non-EoE controls and between children with active (aEoE) and inactive EoE (iEoE). METHODS: Spectral measurements were obtained using a customized pediatric endoscope-compatible fiber-optic Raman probe in real time during an esophagogastroduodenoscopy. Chemometric analysis was performed to identify key Raman features associated with EoE. Pearson correlation analysis was used to assess relationship between the key Raman features and EoE activity indices. Their diagnostic utility was ascertained using the receiver operator characteristic curve analysis. RESULTS: Forty-three children were included in the study (EoE = 32 [74%] and non-EoE control = 11 [26%]; aEoE = 20 [63%] and iEoE = 12 [37%]). Raman intensities assigned to lipids, proteins, and glycogen:protein ratio accurately distinguished children with EoE from those without EoE and aEoE from iEoE. They significantly correlated with EoE activity indices. The Raman peak ratio for lipids had 90.6% sensitivity, 100% specificity, and an area under the curve of 0.95 to differentiate children with EoE from non-EoE controls. The glycogen:protein ratio had 70% sensitivity, 91.7% specificity, and an area under the curve of 0.75 to distinguish children with aEoE from iEoE. DISCUSSION: Real-time intraendoscopy Raman spectroscopy is an effective method for identifying spectral markers reflective of the esophageal biochemical composition in children with EoE. This technique may aid in the diagnosis and monitoring of EoE and help to elucidate EoE pathogenesis.
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Enteritis , Eosinofilia , Esofagitis Eosinofílica , Gastritis , Humanos , Niño , Esofagitis Eosinofílica/diagnóstico , Esofagitis Eosinofílica/patología , Espectrometría Raman , Glucógeno , LípidosRESUMEN
Accurate intraoperative assessment of parathyroid blood flow is crucial to preserve function postoperatively. Indocyanine green (ICG) angiography has been successfully employed, however its conventional application has limitations. A label-free method overcomes these limitations, and laser speckle contrast imaging (LSCI) is one such method that can accurately detect and quantify differences in parathyroid perfusion. In this study, twenty-one patients undergoing thyroidectomy or parathyroidectomy were recruited to compare LSCI and ICG fluorescence intraoperatively. An experimental imaging device was used to image a total of 37 parathyroid glands. Scores of 0, 1 or 2 were assigned for ICG fluorescence by three observers based on perceived intensity: 0 for little to no fluorescence, 1 for moderate or patchy fluorescence, and 2 for strong fluorescence. Speckle contrast values were grouped according to these scores. Analyses of variance were performed to detect significant differences between groups. Lastly, ICG fluorescence intensity was calculated for each parathyroid gland and compared with speckle contrast in a linear regression. Results showed significant differences in speckle contrast between groups such that parathyroids with ICG score 0 had higher speckle contrast than those assigned ICG score 1, which in turn had higher speckle contrast than those assigned ICG score 2. This was further supported by a correlation coefficient of -0.81 between mean-normalized ICG fluorescence intensity and speckle contrast. This suggests that ICG angiography and LSCI detect similar differences in blood flow to parathyroid glands. Laser speckle contrast imaging shows promise as a label-free alternative that overcomes current limitations of ICG angiography for parathyroid assessment.
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Verde de Indocianina , Glándulas Paratiroides , Humanos , Glándulas Paratiroides/diagnóstico por imagen , Glándulas Paratiroides/cirugía , Imágenes de Contraste de Punto Láser , Angiografía , PerfusiónRESUMEN
Biochemical insights into varying breast cancer (BC) phenotypes can provide a fundamental understanding of BC pathogenesis, while identifying novel therapeutic targets. Raman spectroscopy (RS) can gauge these biochemical differences with high specificity. For routine RS, cells are traditionally seeded onto calcium fluoride (CaF2) substrates that are costly and fragile, limiting its widespread adoption. Stainless steel has been interrogated previously as a less expensive alternative to CaF2 substrates, while reporting increased Raman signal intensity than the latter. We sought to further investigate and compare the Raman signal quality measured from stainless steel versus CaF2 substrates by characterizing different BC phenotypes with altered human epidermal growth factor receptor 2 (HER2) expression. Raman spectra were obtained on stainless steel and CaF2 substrates for HER2 negative cells - MDA-MB-231, MDA-MB-468 and HER2 overexpressing cells - AU565, SKBr3. Upon analyzing signal-to-noise ratios (SNR), stainless steel provided a stronger Raman signal, improving SNR by 119% at 1450 cm-1 and 122% at 2925 cm-1 on average compared to the CaF2 substrate. Utilizing only 22% of laser power on sample relative to the CaF2 substrate, stainless steel still yielded improved spectral characterization over CaF2, achieving 96.0% versus 89.8% accuracy in BC phenotype discrimination and equivalent 100.0% accuracy in HER2 status classification. Spectral analysis further highlighted increased lipogenesis and altered metabolism in HER2 overexpressing cells, which was subsequently visualized with coherent anti-Stokes Raman scattering microscopy. Our findings demonstrate that stainless steel substrates deliver improved Raman signal and enhanced spectral characterization, underscoring its potential as a cost-effective alternative to CaF2 for non-invasively monitoring cellular biochemical dynamics in translational cancer research.
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Neoplasias de la Mama , Humanos , Femenino , Espectrometría Raman , Acero Inoxidable/química , Rayos Láser , FenotipoRESUMEN
OBJECTIVES: Compared to adult patients undergoing thyroid surgery, pediatric patients have higher rates of hypoparathyroidism often related to parathyroid gland (PG) inadvertent injury or devascularization. Previous studies have shown that near-infrared-autofluorescence (NIRAF) can be reliably used intraoperatively for label-free parathyroid identification, but all prior studies have been performed in adult patients. In this study, we assess the utility and accuracy of NIRAF with a fiber-optic probe-based system to identify PGs in pediatric patients undergoing thyroidectomy or parathyroidectomy. METHODS: All pediatric patients (under 18 years of age) undergoing thyroidectomy or parathyroidectomy were enrolled in this IRB-approved study. The surgeon's visual assessment of tissues was first noted and the surgeon's confidence level in the tissue identified was recorded. A fiber-optic probe was then used to illuminate tissues-of-interest with a wavelength of 785 nm and resulting NIRAF intensities from these tissues were measured while the surgeon was blinded to results. RESULTS: NIRAF intensities were measured intraoperatively in 19 pediatric patients. Normalized NIRAF intensities for PGs (3.63 ± 2.47) were significantly higher than that of thyroid (0.99 ± 0.36, p < 0.001) and other surrounding soft tissues (0.86 ± 0.40, p < 0.001). Based on the PG identification ratio threshold of 1.2, NIRAF yielded a detection rate of 95.8% (46/48 pediatric PGs). CONCLUSION: Our findings indicate that NIRAF detection can potentially be a valuable and non-invasive technique to identify PGs during neck operations in the pediatric population. To our knowledge, this is the first study in children to assess the accuracy of probe-based NIRAF detection for intraoperative parathyroid identification. LEVEL OF EVIDENCE: Level 4 Laryngoscope, 133:3208-3215, 2023.
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Glándulas Paratiroides , Glándula Tiroides , Adulto , Humanos , Niño , Adolescente , Glándulas Paratiroides/diagnóstico por imagen , Glándulas Paratiroides/cirugía , Glándulas Paratiroides/lesiones , Glándula Tiroides/cirugía , Imagen Óptica/métodos , Paratiroidectomía/métodos , Tiroidectomía/efectos adversos , Tiroidectomía/métodosRESUMEN
Iatrogenic nerve injuries contribute significantly to postoperative morbidity across various surgical disciplines and occur in approximately 500,000 cases annually in the US alone. Currently, there are no clinically adopted means to intraoperatively visualize nerves beyond the surgeon's visual assessment. Here, we report a label-free method for nerve detection using diffuse reflectance spectroscopy (DRS). Starting with an in vivo rat model, fiber- and imaging-based DRS independently identified similar wavelengths that provided optimal contrast for nerve identification with an accuracy of 92%. Optical property measurements of rat and human cadaver tissues verify that the source of contrast between nerve and surrounding tissues is largely due to higher scattering in nerve and differences in oxygenated hemoglobin content. Clinical feasibility was demonstrated in patients undergoing thyroidectomies using both probe-based and imaging-based approaches where the nerve were identified with 91% accuracy. Based on our preliminary results, DRS has the potential to both provide surgeons with a label-free, intraoperative means of nerve visualization and reduce the incidence of iatrogenic nerve injuries along with its detrimental complications.
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Tejido Nervioso , Humanos , Ratas , Animales , Análisis Espectral/métodos , Imagen Óptica/métodos , Microcirugia , Enfermedad IatrogénicaRESUMEN
BACKGROUND: Recent advancements in 3-dimensional patient-derived organoid models have revolutionized the field of cancer biology. There is an urgent need for development of endocrine tumor organoid models for medullary thyroid carcinoma, adrenocortical carcinoma, papillary thyroid carcinoma, and a spectrum of benign hyperfunctioning parathyroid and adrenal neoplasms. We aimed to engineer functionally intact 3-dimensional endocrine patient-derived organoids to expand the in vitro and translational applications for the advancement of endocrine research. METHODS: Using our recently developed fine needle aspiration-based methodology, we established patient-derived 3-dimensional endocrine organoid models using prospectively collected human papillary thyroid carcinoma (n = 6), medullary thyroid carcinoma (n = 3), adrenocortical carcinoma (n = 3), and parathyroid (n = 5). and adrenal (n = 5) neoplasms. Multiplatform analyses of endocrine patient-derived organoids and applications in oncoimmunology, near-infrared autofluorescence, and radiosensitization studies under 3-dimensional in vitro conditions were performed. RESULTS: We have successfully modeled and analyzed the complex endocrine microenvironment for a spectrum of endocrine neoplasms in 3-dimensional culture. The endocrine patient-derived organoids recapitulated complex tumor microenvironment of endocrine neoplasms morphologically and functionally and maintained cytokine production and near-infrared autofluorescence properties. CONCLUSION: Our novel engineered endocrine patient-derived organoid models of thyroid, parathyroid and adrenal neoplasms represent an exciting and elegant alternative to current limited 2-dimensional systems and afford future broad multiplatform in vitro and translational applications, including in endocrine oncoimmunology.
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Neoplasias de las Glándulas Suprarrenales , Neoplasias de la Tiroides , Humanos , Organoides , Microambiente Tumoral , Neoplasias de la Tiroides/patología , Neoplasias de las Glándulas Suprarrenales/patologíaRESUMEN
Importance: Identification and preservation of parathyroid glands (PGs) remain challenging despite advances in surgical techniques. Considerable morbidity and even mortality result from hypoparathyroidism caused by devascularization or inadvertent removal of PGs. Emerging imaging technologies hold promise to improve identification and preservation of PGs during thyroid surgery. Observation: This narrative review (1) comprehensively reviews PG identification and vascular assessment using near-infrared autofluorescence (NIRAF)-both label free and in combination with indocyanine green-based on a comprehensive literature review and (2) offers a manual for possible implementation these emerging technologies in thyroid surgery. Conclusions and Relevance: Emerging technologies hold promise to improve PG identification and preservation during thyroidectomy. Future research should address variables affecting the degree of fluorescence in NIRAF, standardization of signal quantification, definitions and standardization of parameters of indocyanine green injection that correlate with postoperative PG function, the financial effect of these emerging technologies on near-term and longer-term costs, the adoption learning curve and effect on surgical training, and long-term outcomes of key quality metrics in adequately powered randomized clinical trials evaluating PG preservation.
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Hipoparatiroidismo , Glándulas Paratiroides , Humanos , Glándulas Paratiroides/diagnóstico por imagen , Glándulas Paratiroides/cirugía , Glándula Tiroides/diagnóstico por imagen , Glándula Tiroides/cirugía , Verde de Indocianina , Imagen Óptica/efectos adversos , Imagen Óptica/métodos , Tiroidectomía/métodos , Hipoparatiroidismo/etiologíaRESUMEN
During thyroid surgeries, it is important for surgeons to accurately identify healthy parathyroid glands and assess their vascularity to preserve their function postoperatively, thus preventing hypoparathyroidism and hypocalcemia. Near infrared autofluorescence detection enables parathyroid identification, while laser speckle contrast imaging allows assessment of parathyroid vascularity. Here, we present an imaging system combining the two techniques to perform both functions, simultaneously and label-free. An algorithm to automate the segmentation of a parathyroid gland in the fluorescence image to determine its average speckle contrast is also presented, reducing a barrier to clinical translation. Results from imaging ex vivo tissue samples show that the algorithm is equivalent to manual segmentation. Intraoperative images from representative procedures are presented showing successful implementation of the device to identify and assess vascularity of healthy and diseased parathyroid glands.
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Glándulas Paratiroides , Paratiroidectomía , Diagnóstico por Imagen , Imagen Óptica , Glándulas Paratiroides/diagnóstico por imagen , Glándula Tiroides , TiroidectomíaRESUMEN
Background: Accurate assessment of parathyroid gland vascularity is important during thyroidectomy to preserve the function of parathyroid glands and to prevent postoperative hypocalcemia. Laser speckle contrast imaging (LSCI) has been shown to be accurate in detecting differences in parathyroid vascularity. In this surgeon-blinded prognostic study, we evaluate the relationship between intraoperative LSCI measurements and postoperative outcomes of total thyroidectomy patients. Methods: Seventy-two thyroidectomy patients were included in this study. After thyroid resection, an LSCI device was used to image all parathyroid glands identified, and a speckle contrast value was calculated for each. An average value was calculated for each patient, and the data were grouped according to whether the patient had normal (16-77 pg/mL) or low levels of parathyroid hormone (PTH) measured on postoperative day 1 (POD1). The aim of this study was to establish a speckle contrast threshold for classifying a parathyroid gland as adequately perfused and to determine how many such glands are required for normal postoperative parathyroid function. Results: A speckle contrast limit of 0.186 separated the normoparathyroid and hypoparathyroid groups with 87.5% sensitivity and 84.4% specificity: 7 of 8 patients with low PTH on POD1 had an average parathyroid speckle contrast above this limit, while 54 of 64 patients with normal postoperative PTH had an average parathyroid speckle contrast below this limit. Taking this value as the threshold for adequate parathyroid perfusion, it was determined that only one vascularized gland was needed for normal postoperative parathyroid function: 64 of 69 patients (92.8%) with at least one vascularized gland (determined by LSCI) had normal postoperative PTH, while all 3 patients (100%) with no vascularized glands had low postoperative PTH. Overall, the rates of temporary and permanent hypoparathyroidism in this study were 8.3% and 1.4%, respectively. Conclusions: LSCI is a promising technique for assessing parathyroid gland vascularity. It has the potential to help reduce the incidence of hypocalcemia after thyroidectomy by providing surgeons with additional information during surgery to aid in the preservation of parathyroid function.
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Hipocalcemia/prevención & control , Imágenes de Contraste de Punto Láser/métodos , Tratamientos Conservadores del Órgano/métodos , Glándulas Paratiroides/irrigación sanguínea , Glándulas Paratiroides/diagnóstico por imagen , Complicaciones Posoperatorias/prevención & control , Cirugía Asistida por Computador/métodos , Tiroidectomía/métodos , Adulto , Femenino , Humanos , Hipocalcemia/etiología , Periodo Intraoperatorio , Masculino , Persona de Mediana Edad , Glándulas Paratiroides/cirugía , Complicaciones Posoperatorias/etiología , PronósticoRESUMEN
BACKGROUND: Finding and preserving normal parathyroid glands or localizing and removing diseased parathyroid glands are crucial steps to successful thyroid and parathyroid operations. Using near-infrared fluorescence detection to identify parathyroid glands during thyroid and parathyroid operations has lately gained widespread recognition, with 2 Food and Drug Administration-cleared devices currently in the market. We aim to update the endocrine surgery community on how near-infrared fluorescence detection can be most optimally used for rapid intraoperative parathyroid gland identification or preservation. METHODS: A literature review was performed using the key terms: "parathyroid," "near infrared," and "fluorescence" in relevant search engines. Based on the reviewed literature and expert surgeons' opinions, recommendations were formulated for applying near-infrared fluorescence detection to identify or preserve parathyroid glands during cervical endocrine surgery. RESULTS: The scope of near-infrared fluorescence detection can be broadly categorized into (1) using near-infrared auto-fluorescence to identify or locate both healthy and diseased parathyroid glands, and (2) using contrast-enhanced near-infrared fluorescence to evaluate parathyroid gland perfusion. The benefits and pitfalls for both near-infrared-based approaches are described herein. CONCLUSION: Near-infrared fluorescence detection appears helpful for identification and likely preservation of parathyroid glands. We hope these recommendations will be valuable to the practicing endocrine surgeon as they consider incorporating these intraoperative adjuncts in their surgical practice.
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Cuidados Intraoperatorios , Preservación de Órganos , Glándulas Paratiroides/diagnóstico por imagen , Espectrometría de Fluorescencia , Espectroscopía Infrarroja Corta , Toma de Decisiones Clínicas , Medios de Contraste , Manejo de la Enfermedad , Humanos , Cuidados Intraoperatorios/métodos , Sondas Moleculares , Paratiroidectomía , Perfusión , Reproducibilidad de los Resultados , Espectrometría de Fluorescencia/instrumentación , Espectrometría de Fluorescencia/métodos , Espectroscopía Infrarroja Corta/instrumentación , Espectroscopía Infrarroja Corta/métodos , Glándula Tiroides/cirugía , TiroidectomíaRESUMEN
BACKGROUND: Near infrared autofluorescence (NIRAF) detection has previously demonstrated significant potential for real-time parathyroid gland identification. However, the performance of a NIRAF detection device - PTeye® - remains to be evaluated relative to a surgeon's own ability to identify parathyroid glands. METHODS: Patients eligible for thyroidectomy and/or parathyroidectomy were enrolled under 6 endocrine surgeons at 3 high-volume institutions. Participating surgeons were categorized based on years of experience. All surgeons were blinded to output of PTeye® when identifying tissues. The surgeon's performance for parathyroid discrimination was then compared with PTeye®. Histology served as gold standard for excised specimens, while expert surgeon's opinion was used to validate in-situ tissues. RESULTS: PTeye® achieved 92.7% accuracy across 167 patients recruited. Junior surgeons (<5 years of experience) were found to have lower confidence in parathyroid identification and higher tissue misclassification rate per specimen when compared to PTeye® and senior surgeons (>10 years of experience). CONCLUSIONS: NIRAF detection with PTeye® can be a valuable intraoperative adjunct technology to aid in parathyroid identification for surgeons.
Asunto(s)
Periodo Intraoperatorio , Imagen Óptica/métodos , Glándulas Paratiroides/anatomía & histología , Adulto , Anciano , Anciano de 80 o más Años , Competencia Clínica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Glándulas Paratiroides/diagnóstico por imagen , Glándulas Paratiroides/cirugía , Espectroscopía Infrarroja Corta , Adulto JovenRESUMEN
Rapid and accurate response to targeted therapies is critical to differentiate tumors that are resistant to treatment early in the regimen. In this work, we demonstrate a rapid, noninvasive, and label-free approach to evaluate treatment response to molecular inhibitors in breast cancer (BC) cells with Raman spectroscopy (RS). Metabolic reprogramming in BC was probed with RS and multivariate analysis was applied to classify the cells into responsive or nonresponsive groups as a function of drug dosage, drug type, and cell type. Metabolites identified with RS were then validated with mass spectrometry (MS). We treated triple-negative BC cells with Trametinib, an inhibitor of the extracellular-signal-regulated kinase (ERK) pathway. Changes measured with both RS and MS corresponding to membrane phospholipids, amino acids, lipids and fatty acids indicated that these BC cells were responsive to treatment. Comparatively, minimal metabolic changes were observed post-treatment with Alpelisib, an inhibitor of the mammalian target of rapamycin (mTOR) pathway, indicating treatment resistance. These findings were corroborated with cell viability assay and immunoblotting. We also showed estrogen receptor-positive MCF-7 cells were nonresponsive to Trametinib with minimal metabolic and viability changes. Our findings support that oncometabolites identified with RS will ultimately enable rapid drug screening in patients ensuring patients receive the most effective treatment at the earliest time point.