Clinical Trials in Orthopedic Disorders

STUDY PROTOCOL
Year
: 2016  |  Volume : 1  |  Issue : 4  |  Page : 145--151

3D-printed module-assisted minimally invasive lumbar pedicle screw placement: study protocol for a self-controlled, open-label clinical trial with 2-year follow-up


Zheng-xi Yu, Xuan-huang Chen, Guo-dong Zhang, Xu Chen, Chang-fu Wu, Zu-gao Zheng, Xiao-qiang Gao, Hai-bin Lin 
 Department of Orthopedics, Affiliated Hospital of Putian University, Teaching Hospital of Fujian Medical University; Affiliated Putian Hospital of Southern Medical University; Affiliated Hospital of Putian University, Putian, Fujian Province, China

Correspondence Address:
Xuan-huang Chen
Department of Orthopedics, Affiliated Hospital of Putian University, Teaching Hospital of Fujian Medical University; Affiliated Putian Hospital of Southern Medical University; Affiliated Hospital of Putian University, Putian, Fujian Province
China

Abstract

Background: Minimally invasive pedicle screw fixation is an effective treatment for thoracolumbar diseases, but skilled operations are required during the internal fixation. If inaccurate implantation occurs, adverse reactions will appear postoperatively; for example, the implanted screw will fall off. 3D printing can manufacture a suitable implant for a patient, accurately simulate the repair process, and reduce the difficulty and complexity of the operation, aiming to produce an implant that is most suitable for repair surgery. Here, we describe our protocol for testing the hypothesis that precise localization during minimally invasive lumbar pedicle screw placement can be achieved with the assistance of a 3D-printed module. Methods/Design: A single-center, self-controlled, open-label study with 2-year follow-up was carried out at the Affiliated Hospital of Putian University, Putian, Fujian Province, China. Preoperative thin-layer CT data from 36 cases of lumbar spine fixation were collected and digitally reconstructed using Mimics software. An ideal channel for screw insertion via the vertebral pedicle was preset, and a 3D-printed navigation module with a screw channel was designed and printed based on the anatomical structures of the bone surface that could be stripped around the screw channel. Minimally invasive pedicle screw fixation was then navigated by the 3D-printed module using the Quadrant system. A thin-layer CT scan was used for postoperative three-dimensional reconstruction. The primary outcome measure was accurate rate of screw placement, which was used to assess whether the screw placement under navigation by the 3D-printed module achieved the desired results. Secondary outcome measures included lumbar CT results preoperatively, 6 and 24 months postoperatively, operation time, intraoperative blood loss, duration of radiation exposure, and incidence of adverse events at 6 and 24 months postoperatively. Some results from the completed surgery are given below: the time of operation, amount of bleeding and duration of radiation exposure were 120.58 ± 56.46 minutes, 136.83 ± 40.62 mL, and 50 ± 11 seconds, respectively. A total of 186 screws were inserted in the patients, with a 98% accuracy rate. Discussion: The study aims to test our hypothesis that a 3D-printed module is a valuable aid for screw localization in minimally invasive lumbar pedicle screw placement, providing clinical data for 3D-printed module-assisted minimally invasive lumbar surgery using the Quadrant system. Trial registration: ClinicalTrials.gov identifier: NCT02970578. Ethics: The study protocol was approved by the Ethics Committee of the Affiliated Hospital of Putian University, Fujian Province, China, and performed in accordance with the guidelines of the Declaration of Helsinki, formulated by the World Medical Association. Informed consent: Written informed consent was obtained from all participants prior to the trial.



How to cite this article:
Yu Zx, Chen Xh, Zhang Gd, Chen X, Wu Cf, Zheng Zg, Gao Xq, Lin Hb. 3D-printed module-assisted minimally invasive lumbar pedicle screw placement: study protocol for a self-controlled, open-label clinical trial with 2-year follow-up.Clin Trials Orthop Disord 2016;1:145-151


How to cite this URL:
Yu Zx, Chen Xh, Zhang Gd, Chen X, Wu Cf, Zheng Zg, Gao Xq, Lin Hb. 3D-printed module-assisted minimally invasive lumbar pedicle screw placement: study protocol for a self-controlled, open-label clinical trial with 2-year follow-up. Clin Trials Orthop Disord [serial online] 2016 [cited 2019 Aug 25 ];1:145-151
Available from: http://www.clinicalto.com/text.asp?2016/1/4/145/194810


Full Text

 Introduction



History and current related studies

Pedicle screw fixation has been widely used in spinal surgery, in procedures dealing with spinal fractures, lumbar spondylolisthesis, scoliosis, and lumbar spinal stenosis (Schwender et al., 2005; Fan et al., 2015; Shinohara et al., 2016; Toquart et al., 2016; Yang et al., 2016a, b). However, difficulties in pedicle screw placement are unavoidable because of anatomical variations in the spinal structure, as well as spinal degeneration. Consequently, the precise localization for screw placement is essential. If not, errors in screw placement will result in reduced strength or even failure of the internal fixation, which may lead to a series of injuries, including nerve root injury, dural sac tear, vascular injury and even spinal cord injury (Isaacs et al., 2005; Scheufler et al., 2007; Yang et al., 2016a, b). To conclude, improving the accuracy of screw placement and reducing the complications of screw placement during pedicle screw fixation is urgently required.

With the rapid adoption of digital medicine and 3D printing technology in orthopedic practice (Tarafder et al., 2013; Ventola, 2014), 3D techniques, based on preoperative high-resolution CT scan data, can theoretically restore the three-dimensional structure of the bone. That is to say, we can present a detailed description of the complex anatomical structure of the bone, to accurately produce a preoperative plan and an intraoperative simulation (Laine et al., 2000; Kosmopoulos et al., 2007; Tian and Xu, 2009). Wide-ranging evidence that digital three-dimensional reconstruction and 3D techniques can assist the posterior pedicle screw fixation in the treatment of spine lesions has been collected (Lu et al., 2009; Merc et al., 2013; Rόcker et al., 2016).

Main objectives

The main purpose of the study is to explore the accuracy of 3D-printed module-assisted minimally invasive lumbar pedicle screw placement using the Quadrant system, and to verify the feasibility of the module in reducing the error rate of screw placement, as well as postoperative complications.

Distinguishing features from related studies

This study is designed to complete a minimally invasive posterior lumbar pedicle screw placement with the help of 3D printing technology, to achieve the accurate localization of the screw.

 Methods/Design



Study design

A single-center, self-controlled, open-label clinical trial with 2-year follow-up.

Study setting

The Affiliated Hospital of Putian University, Putian, Fujian Province, China.

Study procedures

Thirty-six patients with lumbar degenerative lesions admitted to the Affiliated Hospital of Putian University, China from 2012 to 2015 were enrolled. These patients underwent 3D-printed module-assisted lumbar pedicle screw placement using the Quadrant system, aiming to restore the stability of the spine. Anatomically, imaging results of the spine were used preoperatively to provide a precise localization of the screw placement, and to help achieve a minimally invasive procedure. All the patients were followed up for 6 and 24 months. Three-dimensional reconstruction of the spine was performed based on preoperative and postoperative imaging data. The accuracy rate of screw placement, operation time, intraoperative blood loss and duration of radiation exposure were recorded, and postoperative complications were monitored. These findings were used to assess whether the screw placement achieved the desired results ([Figure 1]).{Figure 1}

Inclusion criteria

Patients of both genders were required to meet all of the following conditions to be included in this trial:

Lumbar degenerative diseases as diagnosed by the criteria for diagnosis of lumbar degenerative diseases (Guigui et al., 1999)Indications for internal fixation in the degenerative lumbar spineLumbar single segment or multi-segment lesionsAverage age 63 yearsProvision of informed consent

Exclusion criteria

Patients presenting with any one or more of the following conditions were excluded from this trial:

Lumbar spine tumors, lumbar tuberculosis, trauma fractures or joint disordersLumbar infection or acute inflammation in other parts of the bodyUnable to undergo lumbar surgery because of surgical contraindications (coagulation disorders) and poor cardiopulmonary function

Baseline analysis

Baseline data, including demographic data and general disease history, were collected from the participants prior to randomization ([Table 1]).{Table 1}

Sample size

Based on our previous experience, we assumed that the accurate rate of screw placement navigated by 3D printed module in 36 patients would be 98%, and totally 216 screws (6 screws per patient) would be used. Considering α = 0.05 (two-sided), β = 0.1, and power = 90%, the final number of screws was calculated to be 322 using PASS 11.0 software (NCSS, MD, USA). With a predicted dropout rate of 20%, the required sample size would be 72 patients with 387 screws. In accordance with the inclusion and exclusion criteria, we finally included 36 patients in this trial.

Recruitment

Potential patients hospitalized in our hospital were informed about the trial through a recruitment advertisement on the hospital bulletin board. Those interested in participating were asked to contact the project investigator via telephone. After providing written informed consent, potential participants who met the requirements of the inclusion and exclusion criteria were enrolled in this study. Patient recruitment began at November 2012, and follow-up data collection will be accomplished until March 2017.

Blinding

This is an open-label study. All participants, surgeons and assessors were informed of therapeutic schedules.

Interventions

Three-dimensional reconstruction: The DICOM data of the lumbar CT scan were input to Mimics 15.0 software and segmented using thresholding and region growing methods.

The three-dimensional reconstruction was completed based on Edit Mask in 3D and Calculate 3D.

Design of the screw channel: The pedicle was longitudinally cut based on Simulation/Cut orthogonal to the Screen , and then the ideal channel for screw insertion was designed. The channel was copied and enlarged to 10 mm with a distance of approximately 70 mm from the talus surface as the support column ([Figure 2]).{Figure 2}

Design and printing of the 3D-printed module: To determine the strippable bone surface, the three-dimensional cutting range (the bone surface around the screw channel exposed by the Quadrant minimally invasive system) included the superior articular process, the mastoid process, the sub-processes and the spine recess. The cut model was enlarged (Simulation/Rescale) 1.2 times to obtain a block module prototype with a thickness of about 4 mm. Module design with the screw channel: the navigation module was obtained using a Boolean operation support column, a block module and the vertebra. The navigation module was exported in STL format and printed by 3D printing technology ([Figure 3]).{Figure 3}

3D-printed module-assisted screw placement: All the implants were made of titanium alloys with high strength, good corrosion resistance and high bone compatibility, and were provided by qualified manufacturers. An incision was made based on the surgical requirements. The general positioning rule is: posterior lumbar interbody fusion, 2.0-2.5 cm from the posterior midline; Pedicle Screws, 3.0-3.5 cm from the posterior midline; transforaminal lumbar interbody fusion, 4.0-4.5 cm from the posterior midline.

A guide pin was inserted towards the correct marking point. The first dilator tube was inserted along the guide pin, which was then pulled out. Successively, other dilator tubes were inserted until the desired diameter was achieved. Afterwards, the Quadrant system was inserted into the bone and fixed. Dilator tubes were removed, and the surgical access was made successfully. We then confirmed again that there were enough skin incisions and deep fascia. Radiance X dual light sources were attached to the left and right channel walls, respectively, aiming to provide ideal lighting conditions for surgery. The Quadrant system was distended, and the support stent was rotated counterclockwise, which could be stretched by 30 mm, allowing the left and right blades of the channel to be stretched up to 55 mm in parallel. According to surgical need, the left and right blades of the channel could be tilted 12 mm to the left and right, to provide sufficient space for minimally invasive spinal surgery. The channel tube was designed to be connected with the fixation system at the top, so that the bottom of the channel tube could be easily tilted to different angles during the operation, depending on the actual needs of the operation.

Following exposure of the surgical field and removal of the surrounding soft tissue, the navigation module was used for surgical localization, the Kirschner wire was inserted and hollow taps were used followed by pedicle screw placement to gradually complete the following procedures: intraoperative decompression, intervertebral fusion, locking the fixation device, fluoroscopy confirmation, and incision suturing. The time of operation, the amount of intraoperative bleeding, and the duration of intraoperative radiation exposure were recorded. Postoperatively, all the patients underwent a lumbar CT scan and three-dimensional reconstruction.

Outcome measures

Primary outcome

The accuracy rate of screw placement, which was used to assess whether the screw placement by 3D-printed module navigation achieved the desired results, was calculated with the following formula: the number of screws placed in the correct direction during the operation/the number of screws predicted by preoperative 3D-printed module design ×100%. A higher value indicates a higher accuracy.

Secondary outcomes

Preoperative and postoperative lumbar CT imaging: To observe the conditions of lumbar fixation.Time of operation: To evaluate the speed of surgery. A shorter operation time indicates that this method was easier to operate.Amount of intraoperative bleeding: To evaluate the conditions of intraoperative blood loss. Less blood loss indicates a higher improvement in the surgical quality by the method being studied. Duration of intraoperative radiation exposure: To evaluate the safety of intraoperative radiation. A shorter duration of intraoperative radiation exposure indicates that this method is conducive to reducing the time of radiation exposure.Incidence of adverse reactions: To evaluate the incidence of postoperative complications.

The schedule of outcome measurement assessment is shown in [Table 2].{Table 2}

Adverse events

Postoperative adverse events were recorded and reported to the Affiliated Hospital of Putian Hospital within 24 hours. Proper therapeutic measures could be performed if the following adverse events occurred, including incision infection, back muscle pain, dural sac tear, vascular injury, nerve root injury, spinal cord injury, screw falling off and loosening.

Data collection, management, analysis, and open access

Baseline data were collected at the day when the participants were enrolled in the study. Other data were collected preoperatively, intraoperatively, postoperatively and during the follow-up. All data were input using Epidata and saved electronically. All data regarding this clinical study were preserved by the Affiliated Hospital of Putian University, China. All data were statistically analyzed by professional statisticians who were responsible for completing an outcome analysis report that was submitted to the project manager who was responsible for completing a research report. An independent data monitoring committee was responsible for data monitoring and management throughout the entire trial.Published data will be released at http://www.figshare.com.

Statistical analysis

All data were statistically analyzed by statisticians using SPSS 19.0 software (IBM Corporation, Armonk, NY, USA) in accordance with the intention-to-treat principle.

Normally distributed measurement data were expressed as means, standard deviations, minimums, and maximums; non-normally distributed data were expressed as lower quartiles, medians, and upper quartiles.

Auditing

Trial progress was reported to the ethics committee of the China Institute of Sport Science every 3 months and was updated in the registration database after each report.

Confidentiality

Valuable trial data were transcribed, dated, and uploaded to a dedicated computer by two staff members. These data were scheduled, checked, locked by an investigator. The locked data could not be altered. Unauthorized persons were unable to access the database. Data reported regarding this trial protocol were preserved by the Affiliated Hospital of Putian Hospital, China.

 Trial Status



Surgery was completed in all the 36 patients with lumbar degenerative lesions who had been admitted at the Affiliated Hospital of Putian University from 2012 to 2015 ([Figure 4]). The time of operation, amount of bleeding and duration of radiation exposure were 120.58 ± 56.46 minutes, 136.83 ± 40.62 mL, and 50 ± 11 seconds, respectively.In total, 186 screws were inserted in the patients, 183 of which achieved the desired results in accordance with the preoperative digital design. The accuracy rate of screw placement was calculated to be 98%. Collection of 2-year follow-up data is still ongoing.{Figure 4}

 Discussion



Significance of the study

The 3D-printed module-assisted minimally invasive lumbar pedicle screw placement used in this study could provide an important basis for guiding the direction of surgery and reducing surgical errors. Its therapeutic efficacy could be confirmed by comparing preoperative and postoperative CT reconstruction images, determining time of operation, intraoperative blood loss, and duration of intraoperative radiation exposure, as well as recording postoperative adverse events.

Limitations

Under the Quadrant system, surgical anatomical landmarks available for identification are limited to a small surgical field of view. Screw placement might only depend on the surgeon's experience, with a certain degree of difficulty. Once a little drift occurs in the screw placement in a narrow channel, it is more likely to cause spinal cord or nerve injury. The small sample size could affect the accuracy of outcome evaluation. In this study, no control group was set up, and there was poor credibility because of a lack of a statistically significant comparison.

Contribution to future studies

This study has shown that a 3D-printed module-assisted minimally invasive lumbar pedicle screw placement can improve the accuracy of screw placement, and reduce radiation injury in patients and surgeons, as there is no need for repeated fluoroscopy or even any radiation during the operation.[18]

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