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

Yibo Chen; Zhaohui Wang; Guiming Fu; Quanxin Wan; Xiaojing Li; Jin Chen

doi:10.3791/64421

Medicine

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

Published: June 9, 2023 doi: 10.3791/64421

Yibo Chen*¹, Zhaohui Wang*¹, Guiming Fu¹, Quanxin Wan¹, Xiaojing Li¹, Jin Chen¹

¹Head and Neck Surgery Department, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China

* These authors contributed equally

Summary

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.

Abstract

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.

Introduction

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.

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Protocol

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

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.
Exclude patients if they do not undergo surgical treatment.

2. Imaging acquisition

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.
Obtain the scan data from the CT system in DICOM format.

3. Computer-aided 3D modeling

Import the data into the 3D visualization software (Figure 1A).
1. Click on the Open button to select the document containing the patient data in DICOM format. Import the data into the software.
2. 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.
Reconstruct different structures in the target area (chest and neck) individually.
1. Select Different Models (for example, skin and bone) in the software according to the structure to be reconstructed (Figure 2A).
2. 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).
3. Click on the Calculation button to complete the preliminary 3D model reconstruction (Figure 2D).
Modify the segmented data.
1. 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.
2. 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).
  NOTE: The 3D modeling is achieved after obtaining the segmentation data of all the structures.

4. Preoperative evaluation

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.
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's expectations and explain the surgeon's treatment plan.

5. Surgery

Remove the tumor according to the preoperative plan and the intraoperative observations of the tumor and the affected vital organs.
Perform tumor-reducing surgery with intraoperative labeling for postoperative adjuvant therapy in the absence of a repair plan.
Repair defects caused by the resection, and perform functional reconstruction as necessary based on the operative plan and intraoperative situation.

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Representative Results

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.

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). Please click here to view a larger version of this figure.

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. Please click here to view a larger version of this figure.

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. Please click here to view a larger version of this figure.

Figure 4: CT images of the sample case. CT revealing that the right subclavian artery (red arrow) is probably encased by a tumor. Please click here to view a larger version of this figure.

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. Please click here to view a larger version of this figure.

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). Please click here to view a larger version of this figure.

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. Please click here to download this Table.

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Discussion

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.

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Disclosures

The authors have nothing to disclose.

Acknowledgments

The authors have no acknowledgments.

Materials

Name	Company	Catalog Number	Comments
Brilliance 256-layer spiral CT system	Philips Healthcare, Andover, MA, USA	N/A	Used for plain and enhanced CT imaging
3D-Matic digital medical software application	Anhui King Star Digital S&T Co. Ltd.	N/A	Used for computer-aided 3D visualization reconstruction

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