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Abstract

Introduction: 3-dimensional (3D) printing and augmented reality (AR) are emerging technologies that are used in a wide variety of scientific fields. Among them, medicine is one of the most promising fields of application since these technologies can benefit not only surgeons, but also medical/surgical trainees, patients and can potentially benefit health care systems with better educated staff working on personalized solutions for the patients. Thus, potentially reducing intra-operative and post operative complications and overall costs for the health care systems. Hepatic malignancy surgeries are some of the most demanding surgeries that could a general surgeon perform. The intra-operative and post-operative risks and complications render them demanding. In literature there are cases of research studies including applications of 3D printing and augmented reality in hepatic malignancies. Methods: For this, a comprehensive literature search was conducted on Scopus and Pubmed databases (latest search September 5, 2024). Research studies that included applications of 3D printing and AR in hepatic malignancies were eligible for the review. Results: Herein, twelve papers have been included and presented, which either include the use of 3D printing or the use of AR. There are some cases where both technologies were used simultaneously. 3D printing technology and AR can be used alone or in combination together to aid in the management of hepatic malignancies. Conclusion: Encouraging results (eg, efforts to reduce cost of 3D printing, proper surgical pre-planning, usefulness in education of medical personnel and patients) from the use of these technologies, not only qualitatively but also quantitatively, show that the medical staff can help patients and improve their part of the health system. Yet much more studies need to validate whether the use of these two technologies provides positive results on the surgeries or not.

Keywords

3-dimensional printing augmented reality hepatic tumors medical training surgical pre-planning

Introduction

What Technology Is for Medicine and the Necessity to Insert Technology to Medicine

Medicine and technology are two communicating vessels, since technology creates and applies theoretical knowledge to aid medicine and medical problems are initiating ideas for a new innovative technology. There are currently, many technological advancements that are aiding medicine or trying to do so. Some of these applications could be, machine learning in fields of medicine,¹ artificial organs,² new interactive platforms for medicine education,³ drug delivery,^4,5 robotic surgery,⁶ 3-dimensional (3D) printing⁷ and many more.

Introduction to 3D Printing

3D printing is straightforward in its concept, it is the procedure where “an object is created by starting with nothing and adding material a layer at a time until you have a completed object”⁸ or “creating an object by building it up layer by layer, rather than machining it away, the way you would by making something from a block of wood, or squirting something into a mold, as you would for injection-molded plastic parts”.⁸ Even though the 3D printing concept is straightforward in simple geometries the difficulty on printing complex geometries rises abruptly. Common problems with printing warping, stringing, over-extrusion and more.⁹ These problems need to be addressed by experienced personnel and the many times a series of efforts and valuable time are necessary.

It is important in 3D printing to gain the best quality of a 3D printed structure. Some quality control measures include the calibration of the printer, the constant and high-quality material selection, the temperature control during printing, the cooling, the support structures, the optimal extrusion speed and printing speed among others. Moreover, a typical layer height for liver for liver 3D printing using fuzed deposition modeling is 0.2 mm. Another important factor is the printing time which in the articles found in this study range from 8-72 h.

3D printing is something with four decades of life. The first working robot 3D printed is credited to Charles W. Hull⁸ created in 1984. Then this printed was commercialized in 1989.⁸ Then the rest is history with many types of 3D printers having been designed till this day. These include digital light projection (DLP), fuzed deposition modeling (FDM), stereolithography (SLA), selective laser sintering (SLS), and others.

Introduction to Augmented Reality

Augmented reality (AR) is a concept related to virtual reality (VR).⁹ The AR was invented by Thomas Preston Caudell in 1992.¹⁰ He developed an AR application to view some assembly diagrams.¹⁰ Using elements from virtual reality, augmented reality superimposes them on the actual world through a live video, which plays on an electronic device's screen.¹¹ In simpler and medical terms AR integrated information regarding the surgical field into surgeons’ mind, so as to aid in the procedure, and simultaneously the surgeon is allowed to maintain direct contact with the environment.¹² As a result, since AR allows for overlaying digital information onto the physical real world, AR is a valuable tool for surgical education and surgical navigation.¹² With the constant development of technology, AR systems have gotten more realistic and portable.¹¹

Scope of This Review

The scope of this review is to find the cases of use of 3D-printing and augmented reality for the use in hepatic malignancies (see Table 1), present them and provide a critical discussion regarding the potential of this technologies and the necessary steps for utilizing these technologies in various fields regarding hepatic malignancies.

Table 1.

Case Studies and Notable Research Papers on 3D Printing and Augmented Reality in Hepatic Malignancy Applications

No.	Source	3-dimensional (3D) printing	Augmented Reality (AR)	Use	Total Patients in study	Basic Outcome	Technical Parameters
1	Valls-Esteve et al,¹³	Yes	No	Pre-surgical planning and simulation training	3 patients	It is shown that 3D-printed soft surgical planning simulators for liver cancer treatment that are accurate and cost-effective can be produced. In the three cases that were reported, the 3D models enabled appropriate pre-operative planning and simulation training, making them an invaluable tool for surgeons.	Printer: Ricoh AM S5500P with layer thickness of 0.08–0.1 mm, Sigma model with dimensional precision of ±0.2 mm and can achieve a layer thickness of 25 μm. Materials used in constructs: PA 12, PLA, Essil 291 Resin. Total production time: 8-24 h. Cost for each construct: 540-583€
2	Lopez-Lopez et al,¹⁴	Yes	No	Teaching, patient communication, and planning of surgery	35 patients	While 3DP hepatic models are useful for education, understanding, and surgical planning, they do not always have an impact on the surgical result. They also show a significant correlation with surgical pathology and CT/MRI.	Materials used in constructs: acrylonitrile butadiene styrene and polyurethane rubber. Total production time: 22 h (IQR:19-25). Cost for each construct: 950€ (IQR: 875-1025)
3	Joo et al,¹⁵	Yes	No	May improve the lesion-by-lesion imaging-pathologic matching for small focal liver lesions, and lead to accurate pathologic tumor staging	20 patients	For small focal liver lesions, a personalized 3D-printed liver model with focal liver lesions may enhance lesion-by-lesion imaging-pathologic matching. This results in precise pathologic tumor staging and a trustworthy reference for imaging-detected focal liver lesions.	−
4	Oshiro et al,¹⁶	Yes	No	Simulate the resection line and safely perform the surgery	Not specified	Compared to previous methods, this method is more economical, took less time to produce, and with increased visibility. They created a new 3D-printed liver for hepatectomy that simplified the process, decreased production costs, and enhanced visibility; this method could be helpful for surgeries in the future.	Printer: EOSINT P760, EOS. Total production time: 72 h to obtain a 3D-printed frame liver model in a flow series. Cost for each construct: US$600
5	Souzaki et al,¹⁷	Yes	No	Surgical simulation	1 patient	They used pre-operative CT scans of an underage that were printed using a 3D printer to create an original 3D liver model. These models enable the use of surgical simulation and make it easier for the surgeon to comprehend the patient's aberrant liver anatomy in situations of big hepatic tumors. These models are anticipated to have several possible uses in diverse medical contexts in the future.	Printer: Objet 500 connex 3 device. Materials used in constructs: acrylic ultraviolet curable resin
6	Giehl-Brown et al,¹⁸	Yes	No	Patient's education	40 patients	Patient satisfaction with surgical education is improved with individual 3D-printed liver models, which also help patients comprehend the surgical process and become aware of potential issues after surgery.	Printer: Ultimaker S5. Materials used in constructs: PLA with a layer height of 0.2 mm for the liver model and PVA for its support
7	Tooulias et al,⁷	Yes	No	Plan complex hepatobiliary surgeries, improve the training of medical students and resident surgeons and fellows and provide more accurate information to tthe patients’ families and the patients themselves	Not specified	A model has been utilized in our university's surgical department to better train medical students, resident surgeons, and fellows, plan complex hepatobiliary procedures, and give patients and their families more accurate information.	−
8	Bonomi et al,¹⁹	No	Yes	Pre-operative surgical plan, pre-operative visualization of 3D reconstructions, use during operation	1 patient	While routine 3D technology use does not promise to transform traditional imaging, it may have a significant impact on multidisciplinary pre-operative planning and intraoperative navigation during complex liver surgery by enabling the surgeon to visualize the patient's anatomy in a dynamic, 3D manner comparable to the surgical field.	−
9	Ribeiro et al,²⁰	Yes	Yes	Aimed to measure the 3D tumor prediction error of Hepataug AR software	1 healthy liver produced 8 virtual livers	The issue of the 2D visual interface of monocular laparoscopy is partially resolved by projecting the tumor toward the operating port, which also increases the precision of AR guidance. Even though AR is less accurate for tumors in the liver's posterior region, it may nonetheless enable surgeons to reach these lesions without fully mobilizing the liver, reducing the surgical trauma.	Printer: Ultimaker 2. Extended Materials used in constructs: PLA. AR software called Hepataug was used.
10	Tang et al,²¹	Yes	Yes	AR: pre-operative surgical planning and additionally, intra-operative navigation in open tumor resection and hemihepatectomy 3D-printing: the model was used intra-operatively as surgical reference	1 patient	The patient was tumor-free based on CT results at the 9-month follow-up examination. Also, no serious postoperative complications occurred.	Object Connex 350 3D Printer was used. Preoperative 3D image reconstruction was performed utilizing the Materialize Mimics, version 16.0, software. Virtual surgery planning was performed utilizing the IQQA-Liver Program. AR Liver Xin was utilized to generate the AR intraoperative video.
11	Wang et al,²²	No	Yes	Laparoscopic operation with the assistance of AR navigation	11 patients	With the aid of augmented reality navigation, laparoscopic right hemi-hepatectomy alongside total caudate lobectomy via the anterior method may be possible and safe for pCCA.	3D visualization software developed by their team was used to reconstruct 3D models and develop a virtual hepatectomy plan. The augmented reality navigation system used was also developed by their team. The PINPOINT™ imaging system or DPM-III-01 imaging system was used in the operation to obtain ICG fluorescence imaging navigation.
12	Huber et al,²³	No	Yes	Navigation system was used for intra-operative computer-assisted 3D-navigation	16 patients / 20 liver tumors	During liver resection, intraoperative navigation is a technology that can be utilized safely. Surgical accuracy is not yet better than the intraoperative orientation standard. The feasibility of the technology will be further enhanced by developments in the form of appropriate deformation algorithms and augmented reality systems.	3D reconstructions performed using MeVis Distant Services. For intraoperative computer-assisted 3D-navigation, the navigation system CAS-One Liver was used.

Methodology

A comprehensive literature search was conducted on two databases (ie, Scopus and Pubmed). The latest search was conducted on September 5, 2024. Various combinations of the terms “3D printing”, “3-dimensional printing”, “Augmented reality”, “Hepatic tumors”, “Hepatic cancer”, “Hepatic malignancies” were used in both databases. One specific search in Pubmed and in Scopus as an example is the following “((3d OR 3-dimentional) AND (printing OR bioprinting)) AND (augmented AND reality) AND ((hepatic OR liver) AND (malignancies OR tumor OR cancer))”. Note that in Scopus the search was within article title-article abstract-keywords. In the review research studies only were included that contained 3D printing and/or AR technology for hepatic malignancies.

3D Printing Applications

Pre-Operative Planning and Surgical Education

Valls-Esteve et al,¹³ presented a novel and low-cost approach to produce patient-specific 3D anatomical models. These were used for hands-on simulation and training. As a result, three hepatic surgeries, where all three livers presented complex hepatic tumors, were planned, with 3D simulators built using 3D printing and silicone molding techniques. Specifically, the tumors were in case #1 biliary tract rhabdomyosarcoma, in case #2 PreText II hepatoblastoma and in case #3 mesenchymal hamartoma.¹³ The 3D physical models demonstrated remarkably accurate replications of the actual condition and proved to be more cost-effective than other models. Finally, their constructs allowed for proper simulation training and pre-surgical planning.¹³

In the multicenter study called LIV3DPRINT, accurate 3D printing of models from original image sources for use in hepatobiliary surgical planning on complex hepatobiliary tumors, patient communication and teaching was validated.¹⁴ In total thirty-five patients from eight centers were included in the study. The centers were from Spain and Germany. The findings of the study, claims that 3D-printing does not affect the surgical outcome necessarily.¹⁴ In addition, the study claim that 3D-printing hepatic models present a good correlation compared with CT/MRI and surgical pathology and they are useful for education, understanding, and surgical planning.¹⁴

In a recent study of Joo et al,¹⁵ the authors aimed to investigate the usefulness of a personalized, 3D-printed, liver model (ie, transparent) with focal liver lesions for lesion-by-lesion imaging-pathologic matching. In this study 20 patients participated. The authors concluded that these personalized, 3D-printed liver model with focal liver lesions may improve the lesion-by-lesion imaging-pathologic matching for small focal liver lesions.¹⁵ This outcome results in accurate pathologic tumor staging and the obtaining of a trustworthy reference for imaging-detected focal liver lesions.¹⁵

Oshiro et al,¹⁶ in their study, developed a novel structure to solve two problems of the creation of a 3D-printed liver model. The one being the cost and the other being the slightly hindered visibility of the inner structures.¹⁶ In their structure the authors did not use transparent loading material to reduce the overall cost and also having the ability to see inside of the structure.¹⁶ The authors performed a hepatectomy using this 3D-printed structure of a liver model. Specifically, they were able to clearly simulate the resection line and safely perform the surgery. The performed hepatectomy using this 3D-printed liver model took place in a patient with liver metastasis after sigmoid colon cancer resection.¹⁶ Overall, their procedure of 3D liver production was cost effective, fast to produce and improved the visibility of the inside of the 3D-printed structures.¹⁶

Another effort (ie, case report) is from Souzaki et al,¹⁷ where the authors conducted an extended left lobectomy to an underage patient diagnosed with PRETEXT IV hepatoblastoma. Even though the tumor was decreased after the neoadjuvant chemotherapy, the hepatoblastoma was still located at the porta hepatis.¹⁷ The lobectomy was undergone after surgical simulation using 3D printing liver model based on pre-operative computed tomography (CT).¹⁷ According to the authors the positional relationships of liver structures, such as blood vessels, and the tumor in the liver were almost completely matched to the real anatomy of the patient's liver. Finally, the tumor was successfully resected completely.¹⁷

Patient's Education

Giehl-Brown et al, conducted a prospective, randomized pilot study.¹⁸ In that study they compared regular patient education to 3D liver model-enhanced (3D-LiMo) surgical education during pre-operative consultation.¹⁸ In most of the cases (ie, 97.5%) the underlying disease, needed hepatobiliary surgery, was a malignancy.¹⁸ The results showed that Patient satisfaction with surgical education is improved by individual 3D-printed liver models as soon as patient education is completed.¹⁸ Furthermore, liver models involve an educational benefit for patients and generally strengthen their participation in the decision-making process.¹⁸

In a technical note published by some of the authors in Tooulias et al,⁷ the researchers tried to make the initial accurate representation of the liver (including parenchyma, vessels, tumors) as a digital 3D model. In addition, created a 1:1 scale 3D print of it, depicting the entire size of the liver with the tumor(s).⁷ The university's surgical department has used one model of this type to plan complex hepatobiliary surgeries, improve the training of medical students and resident surgeons and fellows and finally, provide more accurate information to the families of the patients and the patients themselves.⁷

Augmented Reality Applications

In this case report Bonomi et al,¹⁹ present a case of a 65 y.o. male patient where they mention the practical use of a custom-made 3D model, for a case of bilateral colorectal liver metastases following neoadjuvant chemotherapy.¹⁹ It is mentioned that pre-operative visualization of 3D reconstructions changed significantly the pre-operative surgical plan.¹⁹ In the supplementary material, the authors present how they used the 3D model in an AR setup to aid them in the completion of the surgery and mention that the availability of the 3D model in the operating room was crucial in the surgical field to guide safe surgical pathways.¹⁹ The patient was discharged in the 12^th postoperative day. They report that the pre-operative surgical strategy was drastically altered by the pre-operative visualization of 3D reconstructions.¹⁹

A team located in France has recently developed Hepataug, an AR software.²⁰ It has the ability to project the invisible intrahepatic tumors onto the laparoscopic images and also allows the surgeon to localize them precisely.²⁰ Recently, this team aimed to measure the 3D tumor prediction error of Hepataug. This took place with eight 3D virtual livers. The livers were created from the CT scan of a healthy human liver. The virtual livers were then deformed, and 3D printed to form 3D liver phantoms and these were placed inside a pelvitrainer. Finally, the surgeons had to point the center of eight virtual tumors per liver with a pointing tool. As a result of this work, despite a lower precision of AR for the tumors that were located in the posterior part of the liver, it could allow the surgeons to access these lesions without completely mobilizing the liver. This results in decreasing the surgical trauma.²⁰

In a clinical case report from Tang et al,²¹ the authors utilized AR display technology based on videos to help with surgical resection of hilar cholangiocarcinoma and concomitant left hemihepatectomy. They used enhanced CT and MRCP data to generate 3D images of the patient's hepatic hilar structures. The AR technology was used for the intra-operative navigation during open tumor resection and hemihepatectomy and the pre-operative surgical planning.²¹ Furthermore, pre-operatively, a 3D-printed model of the patient's biliary tree and surrounding vasculature was made using the reconstructed 3D images. The patient over a 9-month follow-up was disease-free and complication-free.²¹

In a recent study of Wang et al,²² 11 patients underwent laparoscopic right hemi-hepatectomy plus total caudate lobectomy with AR navigation technology and the anterior approach being utilized in this operation. The patients had type II or IIIa perihilar cholangiocarcinoma.²² As a result, the right hemi-hepatectomy plus total caudate lobectomy successfully in all 11 patients.²²

Huber et al,²³ conducted a prospective randomized-controlled pilot trial. The researchers aimed with this trial to evaluate computer-assisted 3D-navigation for liver surgery.²³ In the study patients were randomized in two groups (ie, in non-navigated or navigated group) and 20 liver tumors from 16 patients were used for the study to perform open liver resections or primary laparoscopic resections.²³ The navigation system was used for intra-operative computer-assisted 3D-navigation. They came to the conclusion that although surgical accuracy is not yet better than the existing level of intra-operative orientation, intra-operative navigation is a technology that can be employed safely during liver resection.²³ Specifically, they did not find any differences between the navigated and the non-navigated group regarding morbidity, duration of surgery nor length of hospital stay among others.²³

Limitations of the Review

In the current literature review, there are many limitations that can be identified. To begin with, this review is a simple review not a systematic review that follows PRISMA protocol²⁴ or even a systematized review following partially^25,26 PRISMA protocol. In addition, 3D printing technology and the AR technology are presented and acknowledged but close/related technologies such as virtual reality (VR) or 3D bioprinting are not presented. The presented cases were different, and they had a lack of homogeneity in the application of 3D printing and AR technologies thus the presented elements from each study were different.

Current Limitations Future Directions and Works for Further Reading

In the current literature search, there were twelve works presented here. Note that these works present mostly the feasibility in the use of 3D printing and AR. Meaning that the true potential and the benefit or not of these applications have not been tested as a whole. For instance, an idea for a future study would be to use 3D printing and AR technologies combined together or not to see how the learning curve of a team of young surgeons in hepatic surgeries will be using these technologies in comparison to another team of young surgeons not using them. In addition, more qualitative and quantitative elements regarding a surgeon will have to be measured. For instance, the heart rate as an indication for stress should be measured during surgery using these technologies and not using them to see whether they aid the surgeon in his stress management and overall confidence. Additionally, future studies should try to find ways to reduce the overall printing cost and printing time. It is of high importance also for the researchers to include in their research the effort to find one material or a group of materials with more realistic representation of a tissue. This tissue-mimicking material could be a hydrogel. An example of a hydrogel-based 3D printed material can be seen in Liu et al,.²⁷ Artificial intelligence could also be used as a tool in 3D printing and AR to aid in the procedure with a fast segmentation of the scanned body. Moreover, researchers should try to increase the overall anatomic accuracy and simplify the procedure from the beginning till the production of the AR image or the printed model. Furthermore, technologies such as digital twins could be utilized in AR technology in order to have real time organs while performing a procedure such as hepatectomy, which would be used to aid the surgeon and also it could be used to educate and train resident doctors and students how a surgical procedure is in real time. Last but not least, the standardization of the procedures is a key element to make this kind of research comparable from surgical center to surgical center around the world.

Note also that the current understanding and practice of 3D printing in hepatic malignancies has limitations. First of all, the cost of each structure can be high and for some health systems this is a major restriction for the use and spreading of 3D printing. Secondly, specialized equipment and personnel is necessary for the production of the structures. In addition, in urgent surgeries time is limited so the time for the production of a structure with good quality is sometimes larger that the time the surgeons have to start the operation. In this case it is better for the surgical team to opt for the AR technologies.

Finally, to those who want to take a deeper understanding in 3D printing and AR application in hepatic, and not only, surgery there are many works that can be used by the readers to comprehend the use of those two technologies.^12,28-31 Specifically, in the work of Kasai et al,²⁸ the role of 3D printing and virtual reality in liver surgery are discussed. In a recent systematic review¹² in pediatric patients, the enhancement of surgical planning with the aid of 3D visualization techniques is discussed. In addition, a bibliometric analysis²⁹ from 2023 discusses the role of 3D technology in liver cancer resection. Finally, in Gavriilidis et al,³⁰ the state of the art in navigated liver surgery is discussed and in Kościuszko et al,³¹ the pre-operative planning in pediatric liver tumor surgery is discussed. In addition, another concept of 3D printing the so-called 3D bioprinting, where cells and pharmaceutical ingredients are printed in 3D structures, shows an upgrade of 3D printing that can be used for creating more detailed, closer to reality and educational if not functioning structures for liver malignant cases. The readers can find the in vivo applications of 3D bioprinting in the works of Hong et al.³²

Conclusions

In conclusion, the two technologies mentioned in the article (ie, 3D printing technology and AR) can be used and are being in use alone or in combination to contribute in the treatment and management of hepatic malignancies. Till this day there are encouraging results (eg, efforts to reduce cost of 3D printing, improve surgical pre-planning, usefulness in training of medical personnel and in education of patients) from the use of these technologies, which show that the medical staff (eg, resident surgeons, surgeons) can help patients and improve their part of the healthcare system. It is also true that it is necessary for more works to be published to see how helpful or not these two technologies are in the management of the hepatic malignancies and also to provide easier-to-implement technologies with low-cost solutions and with little trained personnel.

Footnotes

Acknowledgments

None.

Author Contributions

Conceptualization, G.T.; methodology, F.F.K. and G.T.; formal analysis, F.F.K.; investigation, F.F.K. and G.T.; data curation, F.F.K., I.-A.K., T.P., V. T., C.P.; writing—original draft preparation, F.F.K.; writing—review and editing, F.F.K., I.-A.K., T.P., V. T., C.P. and G.T.; visualization, F.F.K., I.-A.K., T.P., V.T., C.P. and G.T.; supervision, G.T.; project administration, G.T. All authors have read and agreed to the published version of the manuscript.

Data Availability Statement

Data sharing is not applicable since no new data is generated.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ethics Statement

Not applicable.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

ORCID iDs

Filippos F. Karageorgos

Ion-Anastasios Karolos

Theodoros Pettas

Christos Pikridas

Georgios Tsoulfas

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The Role of 3D Printing and Augmented Reality in the Management of Hepatic Malignancies

Abstract

Keywords

Introduction

What Technology Is for Medicine and the Necessity to Insert Technology to Medicine

Introduction to 3D Printing

Introduction to Augmented Reality

Scope of This Review

Methodology

3D Printing Applications

Pre-Operative Planning and Surgical Education

Patient's Education

Augmented Reality Applications

Limitations of the Review

Current Limitations Future Directions and Works for Further Reading

Conclusions

Footnotes

Acknowledgments

Author Contributions

Data Availability Statement

Declaration of Conflicting Interests

Ethics Statement

Funding

Institutional Review Board Statement

Informed Consent Statement

ORCID iDs

References