The authors have no acknowledgments.

This study protocol was approved by the Ethics Committee of Sichuan Cancer Hospital (Approval date: September 27, 2019). All the procedures involving human participants were performed in accordance with the ethical standards of the institutional and national research committees, as well as the 1964 Declaration of Helsinki and its later amendments. Written informed consent was obtained from all the patients before surgery.
1. Inclusion and exclusion criteria
<ol>
	<li>Include patients if (1) they have pathologically confirmed thyroid cancer and require surgical treatment; (2) they have extensive local tumor infiltration, such as T3-T4 (American Joint Committee on Cancer TNM staging, eighth edition), or if metastatic lesions have invaded important structures such as the trachea, esophagus, and large vessels; (3) they and their family members volunteer for computer-aided 3D visualization; and (4) they had no contraindications to anesthesia.</li>
	<li>Exclude patients if they do not undergo surgical treatment.</li>
</ol>
2. Imaging acquisition
<ol>
	<li>Obtain plain and enhanced CT (including venous and arterial phases) images of the patients using a 256-layer spiral CT system. The scanning parameters are as follows: 120 kV, 120 mA, 512 x 512 matrix, 0.625 mm layer thickness, 150 HU threshold, and 10-20-s arterial scan delay.</li>
	<li>Obtain the scan data from the CT system in DICOM format.</li>
</ol>
3. Computer-aided 3D modeling
<ol>
	<li>Import the data into the 3D visualization software (Figure 1A).
	<ol>
		<li>Click on the Open button to select the document containing the patient data in DICOM format. Import the data into the software.</li>
		<li>Process the data for Gaussian smoothing if the original data contain a lot of image noise (Figure 1B). Select the data with the right mouse button, and then click on the Gaussian Smoothing button.</li>
	</ol>
	</li>
	<li>Reconstruct different structures in the target area (chest and neck) individually.
	<ol>
		<li>Select Different Models (for example, skin and bone) in the software according to the structure to be reconstructed (Figure 2A).</li>
		<li>Set the Color, Maximum Threshold, and Minimum Threshold based on the reconstructed structure on CT (Figure 2B). Set different thresholds for the bone and skin. Adjust the upper and lower thresholds based on the observed preview effect (Figure 2C).</li>
		<li>Click on the Calculation button to complete the preliminary 3D model reconstruction (Figure 2D).</li>
	</ol>
	</li>
	<li>Modify the segmented data.
	<ol>
		<li>Once the segmentation data of structures such as the blood vessels, skin, and bones are obtained (Figures 3A-C), use the Smoothing Algorithm button to optimize the segmented data and ensure the reconstructed saw-tooth edges match the real tissue.</li>
		<li>Then, use the One-Click Navigation button to locate the 2D and 3D images (Figure 3D), and determine whether the segmentation effect was accurate. Use the Pen or Brush tool to fix the incorrect layers (Figure 3E). 
		&#8203;NOTE: The 3D modeling is achieved after obtaining the segmentation data of all the structures.</li>
	</ol>
	</li>
</ol>
4. Preoperative evaluation
<ol>
	<li>View the 3D model, and pay close attention to the tumor volume and location and the relationships between the tumor and the adjacent tissues using the Magnification, Rotation, Tissue Transparency, and Separation functions and a combination of various structures. For example, observe the extent of tumor invasion in the common carotid artery, esophagus, and trachea.</li>
	<li>Determine the scope of surgical resection, the degree of functional impairment after resection, and the postoperative adjuvant therapy plan based on the 3D model evaluation. Implement effective and intuitive doctor-patient communication to satisfy the patient&#39;s expectations and explain the surgeon&#39;s treatment plan.</li>
</ol>
5. Surgery
<ol>
	<li>Remove the tumor according to the preoperative plan and the intraoperative observations of the tumor and the affected vital organs.</li>
	<li>Perform tumor-reducing surgery with intraoperative labeling for postoperative adjuvant therapy in the absence of a repair plan.</li>
	<li>Repair defects caused by the resection, and perform functional reconstruction as necessary based on the operative plan and intraoperative situation.</li>
</ol>

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The authors have nothing to disclose.

For recurrent and metastatic differentiated thyroid carcinoma (DTC), surgical treatment is still preferred17. The 5 year disease-specific survival rate of patients with DTC and R0 resection is 94.4%, which is significantly higher than that of patients with R1 resection (67.9 %)2. Achieving disease control in the neck is crucial for attaining a better quality of life and disease-specific survival for patients4. Medullary thyroid carcinoma is mainly treated with surgery. Therefore, complete tumor resection is of great significance in differentiated and medullary thyroid carcinoma18.
For patients with obvious symptoms such as dyspnea and hemoptysis in whom complete resection is impossible, local palliative surgery can result in optimal conditions for subsequent treatment12. Therefore, surgery has value in the case of extensive local infiltration of thyroid cancer. However, the invasion of several important structures in the neck, such as the trachea, esophagus, common carotid artery, and so on, determines the potential for complete tumor removal; which can subsequently be considered to enable an adequate preoperative evaluation of the treatment plan and the postoperative quality of life. A preoperative evaluation regarding the possibility of residual tumor in advance of postoperative treatment also assists in tumor control5.
Currently, locally advanced thyroid cancer in the neck is typically evaluated using color ultrasonography, CT, and MRI, which are supplemented with fibrolaryngoscopy and esophagoscopy to evaluate the degree of intraluminal involvement of the larynx, trachea, and esophagus5. Color ultrasonography, CT, and MRI yield 2D images, which are limited in their visualization of the tumor volume and invasion. The evaluation of these 2D images requires extensive clinical training and skills. Limitations and uncertainties remain even when such images are evaluated by specialized imaging physicians and experienced surgeons.
The recent development of digital 3D visualization has been actively adopted in medicine, and 3D visualization is currently widely used in hepatocholangiolithiasis, gallbladder cancer, pancreatic head cancer, and retroperitoneal tumors10,19. Compared with traditional 2D images, a comprehensive review of a 3D model using rotation and selective transparency to reveal the tumor tissues and organs allows for a better understanding of the relationships between the tumor and the surrounding tissues. Using such a 3D model, an operative plan can be formulated and practiced, thereby reducing intraoperative bleeding, accelerating preoperative preparation, and providing individualized treatment.
A preoperative 3D model can help clearly define the scope of intraoperative tissue resection, any possible residual tumor, and the likely postoperative organ function, which is advantageous for doctor-patient communication, as well as for ensuring the best prognosis and quality of life for the patients. For example, dyspnea is a common symptom in patients with locally advanced thyroid cancer. The relationship of dyspnea with tumor invasion of the recurrent laryngeal nerve, larynx, and trachea must be evaluated preoperatively4. Differences in the degree of invasion can determine whether tracheotomy and permanent tracheostomy are needed6. Different surgeries directly affect patients' postoperative pronunciation, voice quality, and breathing style20. The accurate preoperative assessment of tumor boundaries can assist in protecting speech and breathing functionality while ensuring complete tumor resection. As CT or MRI cannot be used to judge the depth of airway wall invasion effectively, a 3D model is a good complementary tool for these imaging modalities. Injury to the common carotid artery can even cause death. The 3D model can demonstrate the relationship between the tumor and vessels. Based on this relationship, surgery can be paused, or artificial blood vessels can be prepared.
In locally advanced thyroid cancer, 3D visualization has several advantages. For patients requiring the postoperative repair of the trachea and bone, a 3D model is useful for preoperative surgical simulation, intraoperative surgical guide plate fabrication, and postoperative repair plan formulation. Furthermore, 3D visualization can be used with hybrid virtual reality and other technologies for real-time intraoperative navigation, which allows the overlapping of the 3D model with the patients' actual anatomy.
Although the 3D visualization technology is showing promising clinical results, some limitations remain to be overcome. The estimated cost of 3D modeling is approximately US $410. Different software companies may charge slightly different fees, which increases the costs for patients. Furthermore, there is a learning curve in 3D modeling. Currently, 3D visualization is based on data obtained from 2D technologies, such as CT, MRI, and color ultrasonography. When the contrast between a tumor and the surrounding tissues is inadequate, the boundary images may not be sufficiently accurate, and some small structures may not be clearly displayed.
In conclusion, 3D visualization technology is valuable in the diagnosis and treatment of locally advanced thyroid cancer, the evaluation of the tumor resectability and invasion scope, the planning of the resection and repair, and the assessment of the patient's potential functional damage. This technology can help patients understand their condition and the associated surgical risks and prognosis. Additionally, it can shorten the learning curve for physicians in their early careers. However, the sample size in the current study was small, and long-term follow-up results are lacking. To address the limitations of 3D visualization technology in clinical applications, further research is warranted.

Thyroid cancer is the seventh most common malignancy in China1, and surgery is the most important treatment method2,3. Complete resection of the tumor is strongly associated with high survival rates and a good quality of life in patients with locally advanced thyroid cancer3,4; however, this type of resection is challenging. The neck contains important organs and tissues, such as the trachea, esophagus, and common carotid artery. Resection for advanced thyroid cancer is even more risky and difficult considering the proximity of such tumors to important organs and large blood vessels in the neck and mediastinum5,6. Thus, adequate preoperative evaluation is necessary.
Currently, computed tomography (CT), magnetic resonance (MRI), and color Doppler ultrasonography, which are widely used in clinical settings, provide a two-dimensional (2D) view, which limits the evaluation of the tumor volume, boundaries, and relationships with important surrounding structures7,8. Substantial clinical experience and efficient trial and error are required before surgeons can translate 2D images into 3D space. Computer-aided 3D visualization can use 2D imaging to create a more intuitive 3D model that can be used for preoperative planning and treatment plan selection, thereby making doctor-patient communication more intuitive and reducing doctor-patient disagreements. Although the model provides 3D visualization, it is intangible. This 3D-guided preoperative evaluation and preparation can shorten the surgical time and reduce the surgical risks. The 3D approach has been widely used in hepatobiliary surgery, orthopedics, and oral and maxillofacial surgery9,10. In thyroid cancer, 3D visualization is currently used to assist in ultrasonic diagnosis and in the formulation of surgical plans11,12,13,14,15.
Therefore, we believe that 3D visualization can be conveniently applied to the diagnosis and treatment of locally advanced thyroid cancer. This visualization method includes CT acquisition, computer-aided 3D modeling, and preoperative evaluation using 3D models. The 3D models can be used to determine surgical difficulties, surgical risks, and the potential postoperative functional status. Surgeons can engage in detailed doctor-patient communication, surgical plan formulation, and the corresponding surgical preparation16. Furthermore, this method can provide an adequate preoperative assessment of patients, reduce the surgical risks, and improve patient satisfaction without increasing patient trauma.

<table><tbody><tr><td>Brilliance 256-layer spiral CT system</td><td>Philips Healthcare, Andover, MA, USA</td><td>N/A</td><td>Used for plain and enhanced CT imaging</td></tr><tr><td>3D-Matic digital medical software application</td><td>Anhui King Star Digital S&amp;amp;T Co. Ltd.</td><td>N/A</td><td>Used for computer-aided 3D visualization reconstruction</td></tr></tbody></table>

computer-aided three-dimensional visualization in the treatment of locally advanced thyroid cancer

The diagnosis and treatment of locally advanced thyroid carcinoma are challenging. The challenge lies in the evaluation of the tumor scope and the formulation of an individualized treatment plan. Three-dimensional (3D) visualization has a wide range of applications in the field of medicine, although there are limited applications in thyroid cancer. We previously applied 3D visualization for the diagnosis and treatment of thyroid cancer. Through data collection, 3D modeling, and preoperative evaluation, we can obtain 3D information regarding the tumor outline, determine the extent of tumor invasion, and conduct adequate preoperative preparation and surgical risk assessment. This study aimed to demonstrate the feasibility of 3D visualization in locally advanced thyroid cancer. Computer-aided 3D visualization can be an effective method for accurate preoperative evaluation, the development of surgical methods, shortening the surgical time, and reducing the surgical risks. Furthermore, it can contribute to medical education and doctor-patient communication. We believe that the application of 3D visualization technology can improve outcomes and quality of life in patients with locally advanced thyroid cancer.

From December 2017 to July 2021, 23 patients with locally advanced thyroid cancer underwent 3D modeling. Of these 23 patients, 4 were excluded from surgery owing to surgical risks, and the remaining 19 patients were treated with surgery following 3D modeling (Table 1). All 19 patients had locally advanced thyroid cancer, including 14 for whom this was the initial diagnosis, 16 who had varying degrees of dyspnea, and 18 who had large tumors in the neck (primary thyroid tumor or metastatic lymph node) that had invaded the surrounding tissues. Postoperative pathological evaluation revealed that 11 patients had differentiated thyroid carcinoma, 2 had medullary thyroid carcinoma, 5 had undifferentiated or poorly differentiated thyroid carcinoma, and 1 had papillary thyroid carcinoma with Langerhans cell histiocytosis. The preoperative use of 3D modeling facilitated efficient doctor-patient communication. All the surgeries were successfully completed, and all the postoperative recoveries were smooth, with no perioperative deaths.
As described in the case report in the next subsection, a 3D model has distinct advantages over preoperative CT and intraoperative observations in determining the relationships between the tumor and the blood vessels, trachea, and esophagus. Moreover, it provides accurate information about the presence and scope of tumor invasion.
Sample case presentation 
The cytological analysis of a preoperative puncture biopsy from a 50-year-old man admitted to a hospital for 1 month because of a mass in the right supraclavicular fossa suggested papillary thyroid carcinoma. CT angiography suggested the fusion of multiple lymph nodes in the superior sternal fossa, superior mediastinum, and right cervical root; the wrapping of the right brachiocephalic vein and the lower segment of the right internal jugular vein with the tumor; local narrowing of the right internal jugular vein; displacement and local narrowing of the right subclavian artery; and adjacency of the right common carotid artery to the tumor, with downward involvement of the pleura from that point.
Considering the large number of vessels involved in the tumor, this patient opted to begin treatment with targeted therapy (anlotinib hydrochloride). Re-examination with CT angiography after seven cycles of targeted therapy revealed that compared with the baseline, the multiple fused lymph nodes in the superior sternal fossa and superior mediastinum at the right cervical root had become slightly smaller; the space between the right subclavian artery and right common carotid artery and the tumor had become slightly larger (Figure 4); and the adhesion of the right brachiocephalic vein had decreased.
Using CT data, the surgical team completed computer-aided 3D modeling (Figure 5). The multidimensional evaluation of the 3D model revealed that the tumor had invaded the right internal jugular vein, which had to be resected, and that the removal of a part of the wall of the right subclavian vein was needed, with patency being maintained via direct sutures. No tumor invasion into the right common carotid artery or brachiocephalic trunk was observed. Following targeted therapy, the right subclavian artery remained displaced and showed persistent tumor invasion, meaning this artery had a risk of intraoperative injury. It was determined that intraoperative vascular wall repair or autologous vascular reconstruction could be performed. No obvious tracheal or esophageal invasion was observed.
After adequate preoperative communication, including regarding the potential for massive intraoperative bleeding and upper-right limb dysfunction, the patient agreed to undergo surgery. The right internal jugular vein was excised, and part of the wall of the right brachiocephalic vein was removed during surgery; the lateral wall was subsequently repaired. Intraoperatively, the right subclavian artery was ruptured, and a bridging repair using the right internal jugular vein was performed (Figure 6).
Postoperative pathology suggested a papillary carcinoma with lymph node metastasis (T3bN1bM0, stage I), placing the patient at a high risk of recurrence. Postoperative thyroid-stimulating hormone inhibition and radioactive iodine therapy were recommended. After approximately 1 month, the postoperative swelling of the upper-right limb was resolved, and the right subclavian artery remained unobstructed.
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/64421/64421fig01.jpg" /> 
Figure 1: Importing the data. (A) Data in the DICOM file format are imported into the 3D visualization software by clicking on the Open button (red arrow). (B) If the original data contain a lot of image noise, they are processed in the right menu of the software for Gaussian smoothing (red arrow). <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/64421/64421fig01large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/64421/64421fig02.jpg" /> 
Figure 2: Software reconstruction. (A) The part that will be reconstructed via the threshold algorithm of the software reconstruction module is selected. (B) The Maximum Threshold and Minimum Threshold are set (in red box), along with the Color (yellow arrow). (C) The upper and lower thresholds are adjusted (in red box). (D) The Calculation button is clicked on (red arrow) to complete the preliminary 3D model reconstruction. <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/64421/64421fig02large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/64421/64421fig03.jpg" /> 
Figure 3. Manual correction. (A-C) The segmentation data of the structures, including (A) the blood vessels, (B) skin, and (C) bones, are obtained. (D) The One-Click Navigation button (in the red box) is used to locate the 2D and 3D images (yellow arrow). (E) The accuracy of the segmentation effect is examined. Furthermore, the Pen or Brush (yellow arrow) tool is used to correct the incorrect layers. <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/64421/64421fig03large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 4" class="xfigimg" src="/files/ftp_upload/64421/64421fig04.jpg" /> 
Figure 4: CT images of the sample case. CT revealing that the right subclavian artery (red arrow) is probably encased by a tumor. <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/64421/64421fig04large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 5" class="xfigimg" src="/files/ftp_upload/64421/64421fig05.jpg" /> 
Figure 5: Preoperative evaluation. (A,B) The 3D model reveals a tumor encasing the right internal jugular vein (black arrow) and invading the wall of the right brachiocephalic vein (white arrow). (C) The right subclavian artery remains invaded by the tumor (indicated by the black triangle symbol in Figure 5C); there is no tumor invasion in the right common carotid artery or brachiocephalic trunk. <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/64421/64421fig05large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 6" class="xfigimg" src="/files/ftp_upload/64421/64421fig06.jpg" /> 
Figure 6: Surgery. (A) The right common carotid artery (black arrow) is well protected, whereas the right internal jugular vein and subclavian artery (black triangle) are invaded by the tumor (in black box). (B) The right internal jugular vein is excised, and part of the wall of the right brachiocephalic vein is removed during surgery. A right subclavian artery sleeve resection is completed (white arrow). (C) A bridging repair using the right internal jugular vein is performed (white triangle), whereas the right recurrent laryngeal nerve is repaired using the vagus nerve (white arrow). <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/64421/64421fig06large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
Table 1: Demographics and clinical data of the 19 patients who underwent 3D visualization. Abbreviations: 3D = three-dimensional; PTC = papillary thyroid carcinoma; SCC = squamous cell carcinoma; MTC = medullary thyroid carcinoma; PDTC = poorly differentiated thyroid carcinoma; FTC = follicular thyroid carcinoma. <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/64421/Table 1.xlsx" target="_blank">Please click here to download this Table.</a>

Watch this Scientific Journal Video about Computer-Aided Three-Dimensional Visualization in the Treatment of Locally Advanced Thyroid Cancer at JoVE.com

Computer-Aided Three-Dimensional Visualization in the Treatment of Locally Advanced Thyroid Cancer

In diagnosing and treating locally advanced thyroid cancer, the application of computer-aided three-dimensional reconstruction can provide additional information regarding the tumor scope and anatomic characteristics, thereby assisting in risk assessment and surgical planning.

The diagnosis and treatment of locally advanced thyroid carcinoma are challenging. The challenge lies in the evaluation of the tumor scope and the ...

computer-aided-three-dimensional-visualization-treatment-locally

Universidad San Sebastian

Research

JoVE Journal

Medicine

463 Views.  Affiliated Cancer Hospital of University of Electronic Science and Technology of China. In diagnosing and treating locally advanced thyroid cancer, the application of computer-aided three-dimensional reconstruction can provide additional information regarding the tumor scope and anatomic characteristics, thereby assisting in risk assessment and surgical planning.

Video: Computer-Aided Three-Dimensional Visualization in the Treatment of Locally Advanced Thyroid Cancer

Quantitative Visualization and Detection of Skin Cancer Using Dynamic Thermal Imaging

In 2010 approximately 68,720 melanomas will be diagnosed in the US alone, with around 8,650 resulting in death 1. To date, the only effective treatment for melanoma remains surgical excision, therefore, the key to extended survival is early detection 2,3. Considering the large numbers of patients diagnosed every year and the limitations in accessing specialized care quickly, the development of objective in vivo diagnostic instruments to aid the diagnosis is essential. New techniques to detect skin cancer, especially non-invasive diagnostic tools, are being explored in numerous laboratories. Along with the surgical methods, techniques such as digital photography, dermoscopy, multispectral imaging systems (MelaFind), laser-based systems (confocal scanning laser microscopy, laser doppler perfusion imaging, optical coherence tomography), ultrasound, magnetic resonance imaging, are being tested. Each technique offers unique advantages and disadvantages, many of which pose a compromise between effectiveness and accuracy versus ease of use and cost considerations. Details about these techniques and comparisons are available in the literature 4.
Infrared (IR) imaging was shown to be a useful method to diagnose the signs of certain diseases by measuring the local skin temperature. There is a large body of evidence showing that disease or deviation from normal functioning are accompanied by changes of the temperature of the body, which again affect the temperature of the skin 5,6. Accurate data about the temperature of the human body and skin can provide a wealth of information on the processes responsible for heat generation and thermoregulation, in particular the deviation from normal conditions, often caused by disease. However, IR imaging has not been widely recognized in medicine due to the premature use of the technology 7,8 several decades ago, when temperature measurement accuracy and the spatial resolution were inadequate and sophisticated image processing tools were unavailable. This situation changed dramatically in the late 1990s-2000s. Advances in IR instrumentation, implementation of digital image processing algorithms and dynamic IR imaging, which enables scientists to analyze not only the spatial, but also the temporal thermal behavior of the skin 9, allowed breakthroughs in the field.
In our research, we explore the feasibility of IR imaging, combined with theoretical and experimental studies, as a cost effective, non-invasive, in vivo optical measurement technique for tumor detection, with emphasis on the screening and early detection of melanoma 10-13. In this study, we show data obtained in a patient study in which patients that possess a pigmented lesion with a clinical indication for biopsy are selected for imaging. We compared the difference in thermal responses between healthy and malignant tissue and compared our data with biopsy results. We concluded that the increased metabolic activity of the melanoma lesion can be detected by dynamic infrared imaging.

We demonstrated that malignant pigmented lesions with increased metabolic activity generate quantifiable amounts of heat and the measurement of the transient thermal response of the skin to a cooling excitation allows quantitative identification of melanoma and other skin cancers (vs. non-proliferative nevi) at an early stage of the disease.

In 2010 approximately 68,720 melanomas will be diagnosed in the US alone, with around 8,650 resulting in death 1. To date, the only effective treatment ...

Heterotypic Three-dimensional In Vitro Modeling of Stromal-Epithelial Interactions During Ovarian Cancer Initiation and Progression

Epithelial ovarian cancers (EOCs) are the leading cause of death from gynecological malignancy in Western societies. Despite advances in surgical treatments and improved platinum-based chemotherapies, there has been little improvement in EOC survival rates for more than four decades 1,2. Whilst stage I tumors have 5-year survival rates &gt;85%, survival rates for stage III/IV disease are &lt;40%. Thus, the high rates of mortality for EOC could be significantly decreased if tumors were detected at earlier, more treatable, stages 3-5. At present, the molecular genetic and biological basis of early stage disease development is poorly understood. More specifically, little is known about the role of the microenvironment during tumor initiation; but known risk factors for EOCs (e.g. age and parity) suggest that the microenvironment plays a key role in the early genesis of EOCs. We therefore developed three-dimensional heterotypic models of both the normal ovary and of early stage ovarian cancers. For the normal ovary, we co-cultured normal ovarian surface epithelial (IOSE) and normal stromal fibroblast (INOF)&nbsp;cells, immortalized by retrovrial transduction of the catalytic subunit of human telomerase holoenzyme (hTERT) to extend the lifespan of these cells in culture. To model the earliest stages of ovarian epithelial cell transformation, overexpression of the CMYC oncogene in IOSE cells, again co-cultured with INOF cells. These heterotypic models were used to investigate the effects of aging and senescence on the transformation and invasion of epithelial cells. Here we describe the methodological steps in development of these three-dimensional model; these methodologies aren't specific to the development of normal ovary and ovarian cancer tissues, and could be used to study other tissue types where stromal and epithelial cell interactions are a fundamental aspect of the tissue maintenance and disease development.

Heterotypic Three-dimensional In Vitro Modeling of Stromal-Epithelial Interactions During Ovarian Cancer Initiation and Progression

We describe methodologies for establishing in vitro heterotypic three-dimensional models comprising ovarian fibroblasts and normal ovarian surface or ovarian cancer epithelial cells. We discuss the use of these models to study stromal-epithelial interactions that occur during ovarian cancer development.

Epithelial ovarian cancers (EOCs) are the leading cause of death from gynecological malignancy in Western societies. Despite advances in surgical ...

Human Neuroendocrine Tumor Cell Lines as a Three-Dimensional Model for the Study of Human Neuroendocrine Tumor Therapy

Neuroendocrine tumors (NETs) are rare tumors, with an incidence of two per 100,&#x200A;000 individuals per year, and they account for 0.5% of all human malignancies.1 Other than surgery for the minority of patients who present with localized disease, there is little or no survival benefit of systemic therapy. Therefore, there is a great need to better understand the biology of NETs, and in particular define new therapeutic targets for patients with nonresectable or metastatic neuroendocrine tumors. 3D cell culture is becoming a popular method for drug screening due to its relevance in modeling the in vivo tumor tissue organization and microenvironment.2,3 The 3D multicellular spheroids could provide valuable information in a more timely and less expensive manner than directly proceeding from 2D cell culture experiments to animal (murine) models.
To facilitate the discovery of new therapeutics for NET patients, we have developed an in vitro 3D multicellular spheroids model using the human NET cell lines. The NET cells are plated in a non-adhesive agarose-coated 24-well plate and incubated under physiological conditions (5% CO2, 37 &deg;C) with a very slow agitation for 16-24 hr after plating. The cells form multicellular spheroids starting on the 3rd or 4th day. The spheroids become more spherical by the 6th day, at which point the drug treatments are initiated. The efficacy of the drug treatments on the NET spheroids is monitored based on the morphology, shape and size of the spheroids with a phase-contrast light microscope. The size of the spheroids is estimated automatically using a custom-developed MATLAB program based on an active contour algorithm. Further, we demonstrate a simple method to process the HistoGel embedding on these 3D spheroids, allowing the use of standard histological and immunohistochemical techniques. 
This is the first report on generating 3D spheroids using NET cell lines to examine the effect of therapeutic drugs. We have also performed histology on these 3D spheroids, and displayed an example of a single drug's effect on growth and proliferation of the NET spheroids. Our results support that the NET spheroids are valuable for further studies of NET biology and drug development.

We present a simple agarose overlay platform to grow 3D multicellular spheroids using neuroendocrine cancer cell lines. This method provides a very convenient way to examine the effect of therapeutic drugs on the neuroendocrine tumor cells. It could also help us establish human neuroendocrine tumor spheroids for cancer therapy.

Neuroendocrine tumors (NETs) are rare tumors, with an incidence of two per 100,&#x200A;000 individuals per year, and they account for 0.5% of all human ...

Three Dimensional Cultures: A Tool To Study Normal Acinar Architecture vs. Malignant Transformation Of Breast Cells

Invasive breast carcinomas are a group of malignant epithelial tumors characterized by the invasion of adjacent tissues and propensity to metastasize. The interplay of signals between cancer cells and their microenvironment exerts a powerful influence on breast cancer growth and biological behavior1. However, most of these signals from the extracellular matrix are lost or their relevance is understudied when cells are grown in two dimensional culture (2D) as a monolayer. In recent years, three dimensional (3D) culture on a reconstituted basement membrane has emerged as a method of choice to recapitulate the tissue architecture of benign and malignant breast cells. Cells grown in 3D retain the important cues from the extracellular matrix and provide a physiologically relevant ex&#160;vivo system2,3. Of note, there is growing evidence suggesting that cells behave differently when grown in 3D as compared to 2D4. 3D culture can be effectively used as a means to differentiate the malignant phenotype from the benign breast phenotype and for underpinning the cellular and molecular signaling involved3. One of the distinguishing characteristics of benign epithelial cells is that they are polarized so that the apical cytoplasm is towards the lumen and the basal cytoplasm rests on the basement membrane. This apico-basal polarity is lost in invasive breast carcinomas, which are characterized by cellular disorganization and formation of anastomosing and branching tubules that haphazardly infiltrates the surrounding stroma. These histopathological differences between benign gland and invasive carcinoma can be reproduced in 3D6,7. Using the appropriate read-outs like the quantitation of single round acinar structures, or differential expression of validated molecular markers for cell proliferation, polarity and apoptosis in combination with other molecular and cell biology techniques, 3D culture can provide an important tool to better understand the cellular changes during malignant transformation and for delineating the responsible signaling.

Three dimensional culture of mammary epithelial cells on a reconstituted basement membrane is a useful method to recapitulate the in vivo architecture of the benign breast, and to differentiate the malignant phenotype from the benign breast phenotype. Importantly, this system can be applied to study invasive carcinomas in other tissues.

Invasive breast carcinomas are a group of malignant epithelial tumors characterized by the invasion of adjacent tissues and propensity to metastasize. The ...

Quantification of Breast Cancer Cell Invasiveness Using a Three-dimensional (3D) Model

It is now well known that the cellular and tissue microenvironment are critical regulators influencing tumor initiation and progression. Moreover, the extracellular matrix (ECM) has been demonstrated to be a critical regulator of cell behavior in culture and homeostasis in vivo. The current approach of culturing cells on two-dimensional (2D), plastic surfaces results in the disturbance and loss of complex interactions between cells and their microenvironment. Through the use of three-dimensional (3D) culture assays, the conditions for cell-microenvironment interaction are established resembling the in vivo microenvironment. This article provides a detailed methodology to grow breast cancer cells in a 3D basement membrane protein matrix, exemplifying the potential of 3D culture in the assessment of cell invasion into the surrounding environment. In addition, we discuss how these 3D assays have the potential to examine the loss of signaling molecules that regulate epithelial morphology by immunostaining procedures. These studies aid to identify important mechanistic details into the processes regulating invasion, required for the spread of breast cancer.

Quantification of Breast Cancer Cell Invasiveness Using a Three-dimensional 3D Model

This article provides detailed methodologies for the use of three-dimensional (3D) assays to quantify breast cancer cell invasion. Specifically, we discuss the procedures required to set up such assays, quantification, and data analysis, as well as methods to examine the loss of membrane integrity that occurs when cells invade.

It is now well known that the cellular and tissue microenvironment are critical regulators influencing tumor initiation and progression. Moreover, the ...

A Personalized 3D-Printed Model for Preoperative Evaluation in Thyroid Surgery

The anatomic structure of the surgical area of thyroid cancer is complex. It is very important to comprehensively and carefully evaluate the tumor location and its relation with the capsule, trachea, esophagus, nerves, and blood vessels before operation. This paper introduces an innovative 3D-printed model establishment method based on computerized tomography (CT) DICOM images. We established a personalized 3D-printed model of the cervical thyroid surgery field for each patient who needed thyroid surgery to help clinicians evaluate the key points and difficulties of the surgery and select the operation methods of key parts as a basis. The results showed that this model is conducive to preoperative discussion and the formulation of operation strategies. In particular, as a result of the clear display of the recurrent laryngeal nerve and parathyroid gland locations in the thyroid operation field, injury to them can be avoided during surgery, the difficulty of thyroid surgery reduced, and the incidence of postoperative hypoparathyroidism and complications related to recurrent laryngeal nerve injury reduced too. Moreover, this 3D-printed model is intuitive and aids communication for the signing of informed consent by patients before surgery.

Here, a new method of establishing a personalized 3D-printed model for preoperative evaluation of thyroid surgery is proposed. It is conducive to preoperative discussion, reducing the difficulty of thyroid surgery.

The anatomic structure of the surgical area of thyroid cancer is complex. It is very important to comprehensively and carefully evaluate the tumor ...

Advanced CAD Imaging for Surgical Margin Analysis in Cancer Care

Enhanced Communication of Tumor Margins Using 3D Scanning and Mapping

After oncologic resection of malignant tumors, specimens are sent to pathology for processing to determine the surgical margin status. These results are communicated in the form of a written pathology report. The current standard-of-care pathology report provides a written description of the specimen and the sites of margin sampling without any visual representation of the resected tissue. The specimen itself is typically destroyed during sectioning and analysis. This often leads to challenging communication between pathologists and surgeons when the final pathology report is confirmed. Furthermore, surgeons and pathologists are the only members of the multidisciplinary cancer care team to visualize the resected cancer specimen. We have developed a 3D scanning and specimen mapping protocol to address this unmet need. Computer-aided design (CAD) software is used to annotate the virtual specimen clearly showing sites of inking and margin sampling. This map can be utilized by various members of the multidisciplinary cancer care team.

Author Spotlight: 3D Scanning and Augmented Reality for Enhanced Cancer Surgery Communication

A novel method for 3D scanning and virtual mapping of cancer resections is proposed with the goal of improving communication among the multidisciplinary cancer care team.

After oncologic resection of malignant tumors, specimens are sent to pathology for processing to determine the surgical margin status. These results are ...

Synchronous Visualization of Thyroid Structural and Functional Information

Synchronous Triplanar Reconstruction Integrated with Color Doppler Mapping for Precise and Rapid Localization of Thyroid Lesions

This paper proposes a novel thyroid examination technique based on five-dimensional (5D) synchronous reconstruction of ultrasound data. The raw temporal sequences are reconstructed into 3D volumetric data reflecting anatomical structure. Triplanar visualization from three orthogonal planes is realized to provide a systematic inspection of the entire gland. Color Doppler imaging is integrated into each triplanar slice to map vascularity changes. This multi-modal fusion enables synchronous display of structural, functional, and blood flow information in the reconstructed 5D space. Compared to conventional scanning, this technique offers the benefits of flexible offline diagnosis, reduced dependency on scanning, enhanced intuitive interpretation, and comprehensive multi-aspect evaluation. By minimizing oversight errors, it could improve diagnostic accuracy, especially for novice practitioners. The proposed 5D fusion method allows rapid and precise localization of lesions for early detection. Future work will explore integration with biochemical markers to further improve diagnostic precision. The technique has considerable clinical value for advancing thyroid examination.

Author Spotlight: Integrating Ultrasound Imaging with Biochemical Markers for Thyroid Disease Diagnosis

Here we present a 5D ultrasound technique combining multi-planar 3D reconstruction and color Doppler fusion, which enables synchronous visualization of thyroid structural and functional information. By minimizing blind spots, this method allows rapid, precise localization of lesions to improve diagnostic accuracy, especially benefiting novice practitioners.

This paper proposes a novel thyroid examination technique based on five-dimensional (5D) synchronous reconstruction of ultrasound data. The raw temporal ...

Mixed Reality Assisted Radical Endoscopic Thyroidectomy

Radical endoscopic thyroidectomy (ET) offers superior cosmetic outcomes and enhanced visibility of the surgical field compared to open surgery. However, the thyroid&#39;s unique physiological functions and intricate surrounding anatomy may result in various surgical complications. Mixed reality (MR), a real-time holographic visualization technology, enables the creation of highly realistic 3D models in the real world and facilitates multiple human-computer interactions. MR can be utilized for both preoperative evaluation and intraoperative navigation. First, semi-automatic 3D reconstruction of the neck from enhanced computed tomography images is performed using 3Dslicer. Next, the 3D model is imported into Unity3D to create a virtual hologram that can be displayed on an MR helmet-mounted display (HMD). During surgery, surgeons can wear the MR HMD to locate lesions and surrounding anatomy through the virtual hologram. In this study, patients requiring radical ET were randomly assigned to either the experimental group or the control group. Surgeons performed MR-assisted radical ET in the experimental group. A comparative analysis of surgical outcomes and the results of scales was conducted.&#160;This study successfully developed the neck 3D model and the virtual hologram. According to the NASA Task Load Index Scale, the experimental group exhibited significantly higher scores in &#39;Own Performance&#39; and lower scores in &#39;Effort&#39; compared to the control group (p = 0.002). Additionally, on the Likert Subjective Evaluation Scale, the mean scores for all questions exceeded 3. Although the incidence of surgical complications was lower in the experimental group than in the control group, the differences in surgical outcomes were not statistically significant.MR is beneficial for enhancing performance and alleviating the burden of surgeons during the perioperative period. Furthermore, MR has demonstrated the potential to enhance the safety of ET. Therefore, it is essential to further investigate the surgical applications of MR.

Radical endoscopic thyroidectomy is associated with various surgical complications. This study utilizes mixed reality techniques to assist surgeons in performing radical endoscopic thyroidectomy, aiming to enhance its safety and lower the surgical threshold.

Radical endoscopic thyroidectomy (ET) offers superior cosmetic outcomes and enhanced visibility of the surgical field compared to open surgery. However, ...

Augmented Reality-Based Visualization of a Resected Tumor Specimen

This video demonstrates using augmented reality (AR) for tumor resection, where a 3D-scanned tumor specimen is visualized as a hologram on a head-mounted display. Surgeons can manipulate and lock the hologram in place to ensure precise tumor removal.

All procedures involving sample collection have been performed in accordance with the institute&#39;s IRB guidelines.
NOTE: A schematic detailing the ...

Computer-Aided Three-Dimensional Visualization in the Treatment of Locally Advanced Thyroid Cancer

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Chapters in this video

Quantitative Visualization and Detection of Skin Cancer Using Dynamic Thermal Imaging

Heterotypic Three-dimensional In Vitro Modeling of Stromal-Epithelial Interactions During Ovarian Cancer Initiation and Progression

Human Neuroendocrine Tumor Cell Lines as a Three-Dimensional Model for the Study of Human Neuroendocrine Tumor Therapy

Three Dimensional Cultures: A Tool To Study Normal Acinar Architecture vs. Malignant Transformation Of Breast Cells

Quantification of Breast Cancer Cell Invasiveness Using a Three-dimensional (3D) Model

A Personalized 3D-Printed Model for Preoperative Evaluation in Thyroid Surgery

Enhanced Communication of Tumor Margins Using 3D Scanning and Mapping

Synchronous Triplanar Reconstruction Integrated with Color Doppler Mapping for Precise and Rapid Localization of Thyroid Lesions

Mixed Reality Assisted Radical Endoscopic Thyroidectomy

Augmented Reality-Based Visualization of a Resected Tumor Specimen