Three-dimensional printing and hepatobiliary surgery

Introduction: the introduction of three-dimensional printing in liver surgery

During the last decade, the evolution of advanced imaging methods and computer-based technologies has led to the increased use of three-dimensional (3D) printing in the medical field and especially in general surgery and all the different surgical specialties and subspecialties as well. ^, 3D printing is a process of successive adding of a material in a layer-by-layer way, resembling the conventional inkjet printing. Since 2013, when the first-attempted 3D printing application in liver surgery was described, there have been several important and remarkable efforts in order for 3D printing technology to constitute a valuable tool in liver surgery. Education and training on human organ models, profound study of disease models, education and training of students and residents, preoperative planning, intraoperative assessment of complex surgical operations that demand accuracy, postoperative evaluation, and patient counseling are fields where 3D printing is involved. It appears to be a valuable tool for the surgeon in order to plan complex surgical operations carefully, with great accuracy and with fewer complications.

Despite the significant digital revolution, thanks to which radiology provides the extraction (or acquisition) of highly detailed and informative medical images, the clear understanding of anatomical structures remains puzzling in some cases. However, the comprehension of an organ's anatomy is of outmost importance for the surgeon in order to plan and conduct an operation. That means that the surgeon's team should have at their disposal detailed information, so as to interpret the extracted medical images. The conventional analysis of two-dimensional (2D) images obtained from radiology and the analysis of 3D virtual reconstructions ^, facilitate the anatomical understanding, which still needs to be optimized. Hence, the development of an imaging method that represents the real anatomy of interest in a precise manner is necessary. In this way, the surgeon would be focused on the preoperative planning and the surgical operation itself. 3D printing technology has been targeting the shortcomings of the above methods. Since 1983, when Chuck Hull invented 3D printing, until nowadays, this technology has been used in multiple fields including medicine, where it has led to continuous progress. The inherent accuracy of the 3D printing method, its low cost, and the fact that the images acquired from multidetector computed tomography or magnetic resonance (MRI) could be quickly translated into a physical object of the anatomy of interest justify the broadened range of 3D printing applications in surgery.

The majority of intrahepatic masses requiring resection, in adults, includes hepatocellular carcinoma (HCC) and isolated or few intrahepatic metastases (e.g., colorectal metastasis). According to the World Cancer Report 2014 released by WHO in 2014, HCC ranks first place among all categories of carcinomas based on its prevalence and second place based on its mortality across the world, whereas it is second in prevalence and third in mortality in the Chinese mainland, where it is also first regarding total number of new cases.

HCC is known to be a very serious and complex pathological situation concerning its clinical management, due to its tendency to spread to surrounding intrahepatic structures. There is limited data evaluating the clinical value and feasibility of 3D-printed liver models in HCC and in diagnostic reporting for HCC. Thus, further exploration is needed and warranted especially in cases where a surgical operation is considered as a viable intervention for treatment and reporting of imaging characteristics is crucial. Reviewing the international bibliography, there are no large-scale studies suggesting qualitative and/or quantitative methods so as to meet the need for holistic evaluation of the clinical applications of 3D-printed liver structures apart from small-scale pilot study and/or case studies.

In addition to HCC, the most frequently seen malignant mass in the liver is metastatic liver disease. Liver metastases are tumors that have spread to the liver from other malignant sites. The secondary hepatic tumors are reported to be 18–40 times more common than primary hepatic malignancies in Western populations. The statistics indicate that half of the patients suffering from liver malignancies have primary colorectal cancer (CRC), which constitutes a leading cause of cancer-associated death in Western countries and the third most frequent cause of cancer-related death in the world. Approximately, 25%–30% of patients affected with CRC develop liver metastases during the course of their disease. ^, Apart from CRC, there are also additional primary tumors of the gastrointestinal tract that give rise to secondary liver disease, including esophageal (∼1%–2%) and gastric carcinomas (∼5%–9%), pancreatic and intestinal neuroendocrine tumors (∼1%), biliary tract cancers (∼5%–10%), as well as pancreatic ductal adenocarcinomas (∼14%) and gastrointestinal stromal tumors (<1%). Other malignant sites outside the gastrointestinal tract that lead to liver malignancies include the breast (<1%–2%), lung (12%–20%), kidney (1%–2%) cancers and melanoma (<1%) and are rare. ^, Until nowadays, the estimated 5-year overall survival for all patients with stage IV colorectal cancer is 13%. Treatment approaches for patients with metastatic CRC can be classified as (1) curative or potentially curative (this identifies a group of patients where liver metastases may be resectable), (2) noncurative with active treatment intent (most patients fall into this group), or (3) palliative intent. ^, Unfortunately, despite the progress in oncological medication and surgical techniques, only about 25% of patients affected are amenable to resection, which is regarded as the only way to achieve cure.

The implementation of 3D printing in the field of liver transplantation is extremely interesting. It has been reported that 3D-printed liver models have been used in order to have a tactile structure both of the donor's and the recipient's livers. These models have been used so that the surgeon is able to better identify anatomical landmarks, optimize preoperative planning, and avoid the large-for-size or small-for-size syndrome. Furthermore, it is mentioned that the mean errors of the measurements are <4 mm for the whole liver and <1.3 mm for the diameter of the vessels.

Liver diseases, especially those requiring surgical treatment, have implemented this state-of-the-art technique for many applications in liver surgery. Until nowadays, liver resection constitutes the first-line procedure available for liver cancer that guarantees successful treatment. Regardless of the latest technological progress, liver resection remains a challenging procedure especially for residents and/or young surgeons. The excellent knowledge of liver anatomy is extremely crucial for the different types of intricate liver resections, whether they are anatomical or not. However, each patient is different, meaning that there are always anatomical variations present. Furthermore, the knowledge of the anatomical relationships among the branches of Glisson's sheath, the hepatic veins, and the tumor is essential for safe and accurate liver interventions as well.

The progress made in 3D visualization technology and more updated 3D printing technology has offered more accessible approaches to HCC and/or a variety of liver lesions. Despite the fact that 3D printing method cannot replace the technique, the ability, and the experience of a surgeon, it remains a beneficial technology providing accurate, personalized, graspable, and tactile 3D liver models with the lesion in question. Specifically, 3D-printed liver models may be helpful in the resection of hepatic tumors through demonstrating the relationship of the tumor and its location within hepatic segments with surrounding structures, thus helping with issues such as invasion or proximity to major hepatic or portal veins, arteries, and bile ducts.

The clinical use of the 3D-printed liver models in hepatic surgeries

The liver is an organ with complex anatomy and physiology, rendering the hepatectomy one of the most difficult surgical operations. Thus, 3D models are beneficial to comprehend the liver's complex and highly variable anatomical characteristics. ^, There is a variety of studies in the literature examining the feasibility of the 3D printing liver model's application in the clinical use. The quantitative analysis of these studies have demonstrated the accurate replication of complex liver anatomical structures and tumors with the differences between printed models and original source images or reference images ranging from 0.20% to 20.8%.

There are three stages during a liver resection, when the surgical team can evaluate the clinical use of the 3D liver model and adjust it to the needs of each patient individually. These stages are preoperative, intraoperative, and postoperative. There are plenty of case studies that support that 3D liver models are extremely useful clinical tools during all the stages needed for a liver lesion resection and for living donor liver transplant procedures. ^{, , ,} The majority of available data describe the role of 3D printing in the preoperative stage. ^{, ,} Reviewing the bibliography, there are plenty of studies reporting the use of 3D-printed liver models in order to develop a better understanding of the organ's anatomy, the lesion's location, and surrounding structures' interactions during the preoperative planning. ^{, , , , , , ,}

Preoperatively, the precise anatomical characterization of vascular and biliary network and the volumetric accuracy are necessary in order to plan the surgery with more accuracy and safety. 3D printing technology contributes to that, as it provides detailed imaging of the target anatomy, the geometry, and the volume of the liver. In other words, it provides a mean for getting deeply familiarized with the patient's anatomy prior to surgery. Furthermore, it could help the surgeon evaluate patients with challenging anatomy so as to decrease possible intraoperative complications. Interestingly, it was reported that a minor hepatectomy was avoided as the presence of the 3D model revealed that the tumor was unresectable. There are a lot of reports in the international bibliography that underline the effectiveness of the 3D-printed model when referring to a variety of surgical operations including hepatic surgeries. ^{, , ,} More specifically, the 3D-printed model can help the surgeon localize the targeted part of the liver, delineate the tumor, and specify the resection lines or the dissection planes. Furthermore, the printed models have the advantage of tactile sense, thus allowing the surgeons (students and residents, as well) to practice and plan the resection achieving in this way the goal of personalized and precision medicine.

Admittedly, the majority of the studies report satisfying results regarding the effectiveness of the 3D-printed liver models during the preoperative design. Nevertheless, the absence of randomized controlled trials (RCTs) does not allow a thorough evaluation of all the clinical outcomes.

During the surgical procedure, the presence of the 3D model in the operating room is very helpful for localizing quickly and with advanced accuracy the hepatic tumor(s). The fact that the 3D model is portable is one of the major advantages of 3D printing especially in cases of difficult orientation, where the model serves for intraoperative reassessment ^{, ,} and guidance of intraoperative procedures. In conclusion, the preoperative organization of the hepatic resection with the aid of a 3D model comes with advantages such as the decrease of the surgical time, the reduction of possible intraoperative complications, and the avoidance of blood product transfusions. All the above act cumulatively for minimizing the postoperative complications and the hospitalization period as well.

It is very interesting that the surgeon can not only design the surgical plan but also personalize the postoperative treatment of each patient based on the 3D-printed model.