Received: 8 October 2020 Revised: 8 February 2021 Accepted: 16 March 2021

DOI: 10.1002/hed.26688

ORIGINAL ARTICLE

Short and long-term outcomes of three-dimensional printed

surgical guides and virtual surgical planning versus
conventional methods for fibula free flap reconstruction of
the mandible: Decreased nonunion and complication rates

Matthew M. May MD1 | Benjamin M. Howe MD2 | Thomas J. O'Byrne MAS3 |

Amy E. Alexander MS4 | Jonathon M. Morris MD2,4 | Eric J. Moore MD1 |
1 5 1
Jan L. Kasperbauer MD | Jeffrey R. Janus MD | Kathryn M. Van Abel MD |
Hunter J. Dickens BS4 | Daniel L. Price MD1

1
Department of Otolaryngology-Head and
Neck Surgery, Mayo Clinic, Rochester,
Abstract
Minnesota, USA Background: To determine whether virtual surgical planning and three-
2
Department of Radiology, Mayo Clinic, dimensional printed cutting guides (3D/VSP) improved radiographic bone
Rochester, Minnesota, USA
union compared to conventional methods (CM) in fibula free flap (FFF) recon-
3
Department of Health Sciences Research,
Mayo Clinic, Rochester, Minnesota, USA
struction of the mandibles.
4
Anatomical Modeling Lab, Mayo Clinic,
Methods: Retrospective study from the years 2000–2018 at a tertiary hospital.
Rochester, Minnesota, USA Osseous union was evaluated by a radiologist blinded to each patient's
5
Department of Otolaryngology-Head and treatment.
Neck Surgery, Mayo Clinic, Jacksonville,
Results: Two hundred sixty patients who underwent FFF tissue transfer,
Florida, USA
28 with VSP and 3D cutting guides. Bony union was not achieved in 46 (20%)
Correspondence patients who underwent CM compared to 1 (4%) of patients with VSP and
Daniel L. Price, Department of
Otorhinolaryngology-Head and Neck
guides (p = 0.036). FFF complication was significantly higher in CM with
Surgery, Mayo Clinic, 200 First St. SW, 87 patients (38%) compared to three patients (11%) in 3D/VSP (p = 0.005).
Rochester, MN 55905. Median time to bony union for patients who underwent CM was 1.4 years
Email: price.daniel@mayo.edu
compared to 0.8 years in 3D/VSP.
Funding information Conclusions: 3D/VSP reduced the rate of radiographic nonunion and flap-
Internal departmental funding
related complications in FFF reconstruction for mandibular defects.
Section Editor: Eben Rosenthal
KEYWORDS
3D printing, fibula free flap, head and neck cancer, mandible reconstruction, virtual surgical
planning

1 | INTRODUCTION

The surgical management of mandibular pathology often

The currently submitted manuscript represents original research that
has not been previously submitted and is not under consideration
elsewhere. We performed this research with approval from the Mayo
Clinic Institutional Review Board (IRB 18-008878).
results in large defects and complex wounds that may
require advanced microvascular free tissue transfer. The
purpose of free tissue transfer is to restore both form and
function, and this complex procedure may result in

2342 © 2021 Wiley Periodicals LLC. wileyonlinelibrary.com/journal/hed Head & Neck. 2021;43:2342–2352.
MAY ET AL.
longer operative times and higher complication rates.1
Fibula osteocutaneous free flaps (FFFs) are commonly
used for reconstruction in the head and neck, and these
flaps have the advantage of a long vascular pedicle, versa-
tility of function, and long length of sufficient bone with
reliable blood supply.2,3 Conventional methods (CM) of
FFF reconstruction rely on free hand contouring of the
fibula with estimates of the appropriate angles and length
to match the native mandible, and this technique has
been described as consistently imprecise.4-6 Using thinly
sliced computed tomography (CT), three-dimensional
printed stereolithic models and virtual surgical planning
(3D/VSP) allows preoperative design of osteotomy cutting
guides for the mandible and fibula, providing precise and
expedient mandibular reconstruction. Multiple studies
have shown decreased operative and ischemic times with
3D/VSP compared to CMs.4-9 Osteosynthesis of the FFF
and native mandible is not well discussed in the litera-
ture and long-term benefits have not been established.
Our hypothesis is that 3D/VSP enhances bone-to-bone
contact, improves bony union and reduces plate and
mandibular fracture rates in patients' undergoing FFF
reconstruction for mandibular defects.
2 | METHODS
After obtaining institutional review board approval (IRB#
18-008878), a total of 264 patients who underwent FFF
reconstructive surgery for mandibular defects between the
years 2000–2018 were identified for study at a large single
tertiary care center. Two hundred thirty-two patients
underwent CM of FFF mandibular reconstruction and
32 patients underwent 3D/VSP. We excluded patients
under the age of 18 and patients who did not have ade-
quate postoperative imaging (CT maxilla/face, positron
emission tomography (PET/CT), or Panorex) within
2 years of follow-up (n = 4). Patient demographics, com-
orbidities, pathology, neoadjuvant or adjuvant therapy,
total operative times, and reconstruction times were evalu-
ated. Primary outcome included bony union between
neomandible and FFF of CM compared to 3D/VSP within
2 years of treatment. Secondary outcomes included man-
dibular fracture, mandibular plate fracture, mandibular
plate removal, total operative time, flap take back and total
flap loss, reconstruction time, donor site complications
(skin necrosis, hematoma, infection, wound dehiscence),
major postoperative complications (death, myocardial
infarction, pneumonia, deep venous thrombosis/pulmo-
nary embolism (DVT/PE), stroke), and free flap complica-
tion (hematoma, wound dehiscence, infection, abscess,
vessel thrombosis, pedicle compression, fistula, partial flap
necrosis).
2343
Patients were de-identified to a musculoskeletal
radiologist blinded to each individual patient's treat-
ment paradigm. Radiographic imaging was used to
determine bony union, mandibular fracture, and plate
fracture. Bony union was evaluated between proximal
neomandible and fibula, fibular segments, and distal
neomandible and fibula. Bony union was evaluated using
a scoring system where bone-to-bone contact is given a
score of 1 (callus absent, lucent graft interface visible),
2 (callus present, lucent graft interface visible), or 3 (callus
present, no lucent interface visible), (Table 1). Patients
with a score of 3 indicated bone-to-bone contact with
maximum healing and union. We defined radiographic
nonunion, in the opinion of the treating physicians, as
continued lucent graft interface visibility on follow-up
imaging.
Imaging was preferentially selected for thin-sliced CT
scan of the head neck, thin sliced PET/CT of the head
and neck, followed by Panorex imaging. Each patient
had a minimum of one scan within 2 years of FFF. At
our institution, patients who had mandibular reconstruc-
tion for malignancies routinely received a PET/CT at
1 and 2 years of follow-up. Patients undergoing mandibu-
lar reconstruction for benign pathology routinely
received a CT maxilla/face or Panorex within 2 years of
follow-up. If patients received multiple imaging scans
within 2 years, scans were selected based on the closest
date to the 1 and 2 year follow-up time point from their
surgical date. The median duration of follow-up was
21.5 months (range: 7.4–51. 8). Study data were collected
and managed using a secure web-based software plat-
form, REDCap (Research Electronic Data Capture)
hosted at Mayo Clinic.10
Comparisons of discrete data were made using chi-
square tests or Fisher's exact as appropriate, while contin-
uous variables were compared using Kruskal-Wallis tests.
This cohort included sufficient numbers for comparison
between subgroups in outcomes related to donor site
complications, free flap complications, major complica-
tions, complications resulting from salvage procedure,
and successful bony union. Kaplan-Meier analyses were
used to estimate the number of patients that experienced
each of these events at 1, 2, 5, and 10 years after surgery
and to estimate median survival times in each subgroup,
where possible. Cox proportional hazard models allowed
TABLE 1 Radiographic union of the mandible scale
Grade Callus Lucent graft interface visibility
1 Absent Present
2 Present Present
3 Present Absent
2344
estimation of differences between subgroups in the out-
comes listed above.
2.1 | 3D printing and virtual surgical
planning
Craniofacial anatomy was obtained preoperatively using
a thin cut CT scan, which was used for 3D modeling. The
vascular supply to the lower leg was evaluated preopera-
tively using intravenous contrast enhanced CT scans with
three-vessel runoff of the lower extremity. These scans
were used to create the FFF reconstruction plan based on
the proposed mandibular osteotomies. ProPlan CMF
(Materialise, Leuven, Belgium) was used to digitally plan
resections and FFF reconstructions. All cutting guides
and models were 3D printed in Dental SG resin on Form
2 vat photopolymerization printers (Formlabs, Boston,
MA, USA) and sterilized prior to use in the operating
room. By leveraging the surgical expertise and input
alongside the radiological foundation and with techno-
logical assistance from the engineers, precision models
and guides are created at the point of care within minutes
from the operating room. The on-site location and prox-
imity of the Anatomic Modeling Lab to the surgical suites
is paramount to this collaboration and helps the care
team plan and schedule surgeries quickly.
2.2 | Surgical technique
A two-team surgical approach for concurrent tumor abla-
tion and reconstruction was utilized. The FFF was then
harvested as previously described.11 Tourniquet pressure
was routinely inflated to 350 mm Hg. The skin paddle
location varied depending on the perforating vessels but
was predominantly centered between the lower and mid-
dle third of the leg. A split thickness skin graft from the
ipsilateral thigh was used for donor sites that were unable
to be closed primarily. A wound vacuum (V.A.C.) was
placed on the split thickness skin grafted donor site.
For patients undergoing CM FFF reconstruction, a
2.0 mm titanium mandibular reconstruction plate was
contoured to the native mandible when possible prior to
creating any osteotomies and adjustments were made
based upon individual patient anatomy and occlusion
considerations to ensure maintenance of the shape of the
neomandible. If adaptation of the plate to the mandible
was impossible, secondary to a large exophytic tumor for
example, the plate was contoured after mandibular resec-
tion. The plate was then removed and tagged to ensure
correct orientation for refixation, osteotomies performed
free hand, and margins cleared if malignancy was
MAY ET AL.
present. The FFF would then be harvested and contoured
the mandibular defect using hand measurements and/or
popsicle sticks as sizing guides. The prebent plate would
be refixed to the native mandible using the previously
drilled holes. The FFF segments were then secured to the
plate and the vessels draped into the neck.
For patients undergoing FFF with 3D/VSP, a 3D
printed cutting guide was routinely secured to the mandi-
ble with monocortical screws. Using VSP planned cutting
guides, osteotomies were made and margins cleared via
frozen pathology for malignancies. A titanium 2.0 mm
titanium reconstruction plate was contoured to the 3D
printed anatomic model of the mandible with the defect
size mirroring that planned using the 3D cutting guides.
If additional margins were required from the patient,
these could then be replicated in the model, allowing for
intraoperative flexibility. Fibular osteotomies were made
using 3D printed cutting guides. The fibula segment(s)
were then fixed to the plate to ensure bone-on-bone con-
tact. Once complete, the titanium plate with the FFF
secured in position was brought to the patient table and
inset and plated to the native mandible and the vessels
were draped into the neck. Following plating and skin
paddle inset, microvascular anastomosis was performed.
A Cook-Swartz Implantable Doppler (Cook Vascular
Incorporated, Vandergrift, PA) was placed distal to the
arterial anastomosis for all patients after 2005. Total
reconstructive time was defined from the deflation of the
lower extremity tourniquet to the end of the operation.
Figures 1 and 2 provide examples of VSP and the applica-
tion of 3D printed models in surgery.
3 | RESULTS
Among the 260 patients studied, 232 patients underwent
CM FFF reconstruction whereas 28 patients underwent
FFF with 3D/VSP. A detailed summary of demographic,
comorbidity, radiation and/or chemotherapy, and pathol-
ogy comparisons between subgroups is shown in Table 2.
Age at diagnosis, sex, marital status, ethnicity, body mass
index, and comorbidities were not significantly different
among cohorts (Table 2).
Comparisons of outcomes and surgical characteristics
are shown in Table 3. Bony union was significantly
higher with 3D/VSP compared to CM (p = 0.036). We
found a 20% (46/232) nonunion rate in the CM compared
to 3.6% (1/ 28) nonunion rate in the 3D/VSP. After
adjusting for age, sex, and adjuvant therapy (radiation,
chemotherapy), the significant difference in bony union
persisted with patients undergoing 3D/ VSP twice as
likely (HR = 1.95, 95% CI = 1.29–2.94, p = 0.005) to
achieve bony union than the CM group. Median time to
MAY ET AL. 2345

TABLE 2 Patient demographics

CM (N = 232) 3D printing and VSP (N = 28) Total (N = 260) p value

Age at diagnosis 0.2229a
Mean (SD) 56.3 (14.61) 57.3 (19.78) 56.4 (15.21)
Median (IQR) 59.0 (49.0–66.0) 65.0 (48.0–71.0) 59.0 (49.0–67.0)
Sex, n (%) 0.1795b
Male 154 (66.4%) 15 (53.6%) 169 (65.0%)
Female 78 (33.6%) 13 (46.4%) 91 (35.0%)
Marital status, n (%) 0.1856c
Married 154 (66.4%) 16 (57.1%) 170 (65.4%)
Divorced 20 (8.6%) 2 (7.1%) 22 (8.5%)
Widowed 16 (6.9%) 2 (7.1%) 18 (6.9%)
Single 40 (17.2%) 6 (21.4%) 46 (17.7%)
Ethnicity, n (%) 0.4455c
White 210 (90.5%) 25 (89.3%) 235 (90.4%)
Black 3 (1.3%) 2 (7.1%) 5 (1.9%)
Hispanic 3 (1.3%) 0 (0.0%) 3 (1.2%)
Asian 4 (1.7%) 0 (0.0%) 4 (1.5%)
Native American 2 (0.9%) 0 (0.0%) 2 (0.8%)
Other 4 (1.7%) 0 (0.0%) 4 (1.5%)
Body mass index 0.8184a
Mean (SD) 26.6 (5.53) 26.3 (5.54) 26.6 (5.52)
Median (IQR) 25.7 (22.5–29.7) 25.9 (22.0–30.2) 25.8 (22.5–29.7)
Comorbidities, n (%)
Diabetes 15 (6.5%) 3 (10.7%) 18 (6.9%) 0.4229c
Chronic renal disease 5 (2.2%) 0 (0.0%) 5 (1.9%) 1.0000c
Peripheral vascular disease 6 (2.6%) 3 (10.7%) 9 (3.5%) 0.0605c
Autoimmune disease 11 (4.7%) 1 (3.6%) 12 (4.6%) 1.0000c
Obstructive sleep apnea 9 (3.9%) 0 (0.0%) 9 (3.5%) 0.6034c
Hypertension 84 (36.2%) 10 (35.7%) 94 (36.2%) 1.0000c
Hypercholesterolemia 52 (22.4%) 5 (17.9%) 57 (21.9%) 0.8090c
Pathology, n (%) 0.7576c
Squamous cell carcinoma 133 (59.6%) 16 (57.1%) 149 (59.4%)
Osteoradionecrosis 35 (15.1%) 4 (14.3%) 35 (13.9%)
Osteomyelitis 28 (12.6%) 4 (14.3%) 32 (12.7%)
Salivary tumor 10 (4.5%) 0 (0.0%) 10 (4.0%)
Osteosarcoma 10 (4.3%) 2 (7.1%) 8 (3.2%)
Cutaneous basal cell 2 (0.9%) 0 (0.0%) 2 (0.8%)
Cutaneous melanoma 1 (0.4%) 0 (0.0%) 1 (0.4%)
Other tumord 12 (5.4%) 2 (7.1%) 14 (5.6%)
Radiotherapy, n (%) 82 (35.5%) 15 (55.6%) 97 (37.6%) 0.0417b
Chemotherapy, n (%) 50 (21.6%) 6 (23.1%) 56 (21.8%) 0.8668b

Abbreviations: CM, conventional methods; IQR, interquartile range; VSP, virtual surgical planning.
a
Kruskal-Wallis p value.
b
Chi-square p value.
c
Fisher exact p value.
d
Ameloblastoma, fibrosarcoma, rhabdomyosarcoma, odontogenic keratocyst, spindle cell sarcoma, myxofibrosarcoma, renal cell carcinoma, osteoblastoma,
anaplastic meningioma.
2346 MAY ET AL.

TABLE 3 Comparisons of outcomes

3D printing and
CM (N = 232) VSP (N = 28) Total (N = 260) p value
Bony union, n (%) 0.036a
No 46 (19.8%) 1 (3.6%) 47 (18.1%)
Yes 186 (80.2%) 27 (96.4%) 213 (81.9%)
Mandible fracture, n (%) 0.606a
No 222 (95.7%) 28 (100.0%) 250 (96.2%)
Yes 10 (4.3%) 0 (0.0%) 10 (3.8%)
Mandibular plate fracture, n (%) 0.487a
No 209 (90.1%) 27 (96.4%) 236 (90.8%)
Yes 23 (9.9%) 1 (3.6%) 24 (9.2%)
Mandibular plate removed, n (%) 0.101a
No 173 (74.6%) 25 (89.3%) 198 (76.2%)
Yes 59 (25.4%) 3 (10.7%) 62 (23.8%)
Donor site complication, n (%) 0.547a
No 203 (87.5%) 26 (92.9%) 229 (88.1%)
Yes 29 (12.5%) 2 (7.1%) 31 (11.9%)
Free-flap complication, n (%) 0.005a
No 145 (62.5%) 25 (89.3%) 170 (65.4%)
Yes 87 (37.5%) 3 (10.7%) 90 (34.6%)
Infection 25 1
Partial flap necrosis 19
Fistula 18
Pedicle compression 2
Hemorrhage 15 1
Vessel thrombosis 6
Wound dehiscence 16 1
Major medical postoperative complication, 0.777a
n (%)
No 199 (85.8%) 25 (89.3%) 224 (86.2%)
Yes 33 (14.2%) 3 (10.7%) 36 (13.8%)
Flap take back operation, n (%) 0.274a
No 195 (84.1%) 26 (92.9%) 221 (85.0%)
Yes 37 (15.9%) 2 (7.1%) 39 (15.0%)
Total flap loss
Yes 9 (3.87%) 1 (3.57%) 10 (3.84%)
Total operating room time (min) 0.004b
Mean (SD) 561.5 (123.93) 490.7 (117.88) 553.9 (125.00)
Median (IQR) 548.0 (465.0–650.0) 483.0 (391.0–562.0) 546.0 (463.0–643.0)
Total reconstructive time (min) 0.004b
Mean (SD) 293.5 (89.94) 250.2 (70.40) 288.9 (88.95)
Median (IQR) 285.5 (243.0–342.0) 233.0 (216.0–284.0) 281.0 (231.0–339.0)
Composite outcome, n (%) 0.023a
No 87 (37.5%) 17 (60.7%) 104 (40.0%)
Yes 145 (62.5%) 11 (39.3%) 156 (60.0%)

Abbreviations: CM, conventional methods; IQR, interquartile range; VSP, virtual surgical planning.
a
Chi-square p value.
b
Kruskal-Wallis p value; significant at p < 0.05.
MAY ET AL. 2347

F I G U R E 1 VSP with computer aid design of 3D printed cutting guides. CT imaging is segmented to anatomically outline soft tissue,
bone, and tumor. Precise osteotomy sites are planned for a customized treatment plan (A). Angulation and length of fibular segments is
optimized for form and function of FFF inset (B). Customized cutting guides are designed for both mandible and fibula segments (C, D). CT,
computed tomography; FFF, fibula free flap; VSP, virtual surgical planning [Color figure can be viewed at wileyonlinelibrary.com]

bony union for patients who underwent CM was
1.4 years (range: 0.2–17.5). Median time to bony union in
patients undergoing 3D/ VSP was 0.8 years (range: 0.01–
2.6). Although both surgical procedures often resulted in
bony union, the group that underwent 3D/ VSP took sig-
nificantly less time.
FFF complication rates were significantly higher in
the CM group at 38% (87/232) compared to 11% (3/28) in
the 3D/VSP group (p = 0.005). After adjusting for age,
indication for surgery, sex, and (neo)adjuvant therapy,
the estimated risk of FFF complication for patients with
3D and VSP were approximately 73% less than for those
undergoing CM (HR = 0.3, 95% CI = 0.09–0.95,
p = 0.04). There was no significant difference in mandib-
ular fracture rate, plate fracture, hardware removal, or
donor site complication. The composite likelihood of
mandibular fracture, plate fracture, hardware removal,
nonunion, major medical complication, free flap compli-
cation, donor site complication, and flap take back opera-
tion was significantly reduced in 3D/VSP patients (39%
vs. 63%, 11/28 vs. /232, p = 0.023). Table 4 illustrates a
cumulative incidence at 1, 2, 5, and 10 years for both FFF
complications and bony union. The time of the imaging
scan at which bony union was evaluated for each group
including mean, SD, median, minimum and maximum
of imaging scan is included in Table 4. Surgical time
including both total operative time (incision to closure)
and total reconstructive time for patients in the 3D/VSP
group were significantly faster compared to the CM
group, p = 0.004 and p = 0.004. Total operative time for
3D/VSP was 491 min (8.2 h) versus CM at 562 min
(9.4 h), with lower variability (118 vs. 124 min). Total
reconstructive time was 250 min versus 294 min, again
with lower variability (70 vs. 90 min).
The number of fibular segments was analyzed as a
surrogate for reconstruction complexity. Fibular seg-
ments used for reconstruction were classified as a single
bone segment or multiple bone segments of two or more.
There was similar proportions of single segment and mul-
tisegments between the VSP/3D (n = 10 single segment,
n = 18 multisegment) and the CM group (n = 64 single
segment, n = 154 multisegment). No significant
2348 MAY ET AL.

F I G U R E 2 Intraoperative utilization of 3D printed cutting guides and FFF reconstruction. Customized cutting guides are inserted onto
the mandible for precise osteotomy sites for resection (A, B). After harvest of the FFF, planned angles for optimal FFF inset are created using
the cutting guides. 3D printed modeling is used for accuracy of reconstruction and optimal hardware placement. FFF, fibula free flap [Color
figure can be viewed at wileyonlinelibrary.com]

T A B L E 4 Cumulative incidence for

Cumulative incidence, % (95% CI)
free flap complication, bony union, and
Event CM 3D/VSP time to imaging
Free flap complication (N = 232, Events = 87) (N = 28, Events = 3)
1 year 37% (30%–43%) 4% (0%–7%)
2 years 39% (32%–46%) 5% (1%–9%)
5 years 41% (34%–48%) 10% (3%–16%)
10 years 43% (35%–50%)
Bony union (N = 232, Events = 186) (N = 28, Events = 27)
1 year 40% (34%–46%) 66% (43%–80%)
2 years 70% (62%–75%) 89% (67%–96%)
5 years 95% (89%–97%)
10 years 97% (87%–99%)
Bony union, n (%)
No 46 (19.8%) 1 (3.6%)
Yes 186 (80.2%) 27 (96.4%)
Time to bony union (years)
Mean (SD) 1.4 (1.43) 0.9 (0.58)
Median (IQR) 1.2 (0.6–2.0) 0.8 (0.6–1.2)
Time to imaging (years)
Mean (SD) 1.5 (0.89) 1.0 (0.57)
Median (IQR) 1.4 (0.8–2.0) 0.8 (0.6–1.2)

Abbreviations: 3D/VSP, three-dimensional printed stereolithic models and virtual surgical planning; CI,
confidence interval; CM, conventional methods; IQR, interquartile range.
MAY ET AL.
relationship was found (chi-square p value = 0.4899),
indicating that the number of segments were not signifi-
cantly associated with the subgroups. Further subgroup
analysis failed to demonstrate any significant difference
in the number of segments and outcomes of complica-
tions and bony union.
Sensitivity analyses were conducted examining the
potential for era effects. Year effects were found in donor
site complication (HR = 0.91, 95% CI = 0.85–0.98,
p = 0.02) and free flap complication (HR = 0.95, 95%
CI = 0.91–0.99, p = 0.03) indicating decreasing hazard
for these complications over time. No year effects were
found for major complications, flap take back operation,
or bony union. However, when controlling for year in
comparison of CM versus 3D/VSP, FFF complications
remained marginally significant (HR = 0.34, 95%
CI = 0.10–1.13, p = 0.08, significance p < 0.1) and bony
union remained highly significant (HR = 1.92, 95%
CI = 1.22–3.03, p = 0.005, significance p < 0.05). These
results indicate that rates of FFF complications were an
estimated 66% lower, and bony union was an estimated
92% higher, in the 3D/VSP cohort after controlling for
differences across the study timeframe. However, there
was limited information that allowed a direct comparison
between these procedures in the same timeframe.
4 | DISCUSSION
3D model printing and VSP (3D/VSP) reduces the rate of
radiographic nonunion and flap-related complications in
patients undergoing FFF reconstruction for mandibular
defects when compared to CM of free hand contouring.
Total operative time and reconstructive time was signifi-
cantly less in 3D/VSP patients. Moreover, the time to
bony union improved from 1.4 years with CM to 0.8 years
with the 3D/VSP, which was statistically significant. Pre-
cision osteotomies with the stereolithic cutting guides
allow for more bone-to-bone contact between fibular
bone segments and mandible, and this increased contact
likely contributes to enhanced bony union.
In most cases, mandibular union occurs in 4–8 weeks
depending on the age of the patient.12 In brief, inflamma-
tory cells and new capillaries invade the fracture, and
osteogenic cells form an interwoven pattern of bony tra-
beculae extending from the bone segments toward one
another to form a callus. Calcium is deposited into the
callus and woven bone is replaced by lamellar bone to
form bony union. If there is disruption at any one of
these stages of wound healing, fibroblasts will form an
investing layer across bone segments and prevent osteo-
genic bony union.12 Previous studies in craniofacial
trauma have illustrated that nonunion could lead to
2349
incapacitating effects on patients' quality of life including
pain, discomfort, physical appearance, mental health,
deterioration of physical function, malocclusion, bone
atrophy, and weakening.12-14 Therefore, techniques to
optimize bony union such as 3D/VSP could significantly
improve patients' quality of life.
In our study, 20% of patients in the FFF CM group
had nonunion which is consistent with prior studies
investigating bony union in FFF reconstruction.15,16
Chang et al investigated outcomes of prebent plates on a
stereolithic model compared to VSP and prefabricated
cutting guides.17 In this study, there was no significant
difference in complication rates between the two groups;
however, VSP led to less burring, fewer osteotomy revi-
sions, and less bone grafting compared to stereolithic
models with a prebent plate. The authors found a signifi-
cant difference in rate of nonunion at 18.6% in patients
who had mandibular reconstruction by using a prebent
plate compared to VSP with cutting guides at 4.1%. Our
study differs in that we compared CM to 3D/VSP instead
of prebending mandibular plates between treatment
methods. Moreover, the authors defined bone nonunion
as a gap in bony segments greater than 2 mm via CT at
1 year, which is different from our definition in our
study.
Bony union remains a subjective topic. There is sig-
nificant disagreement among clinicians regarding when a
fracture has healed. Ultimately, we chose a relatively
arbitrary time point for uniformity and to capture follow-
up imaging in as many patients as possible. Tumor recur-
rence, death, lack of late follow-up cross-sectional imag-
ing all limit the ability to uniformly compare patients at
later time points. The lack of standardized definition of
union can lead to questionable or controversial results.18
The U.S. Food and Drug Administration (FDA) defines a
nonunion as a fracture that is at least 9 months old and
has not shown any signs of healing for three consecutive
months.19 There is no standardized definition of union of
the mandible and to the best of our knowledge, there are
no validated clinical or radiographic studies of mandibu-
lar nonunion. Hypertrophic nonunion is described as a
callus formation around a fracture site.20 This is thought
to be due to micromotions at the fracture site. Atrophic
nonunion is defined as minimal or absent callus forma-
tion at the fracture site.20 Both of these nonunions may
have the fracture line lucency on radiographic imaging.
Previous research in the orthopedic literature has
attempted to define nonunion by using radiographic
instruments. Radiographic union score for hip (RUSH) is
a previous validated outcome instrument designed to
improve intra- and interobserver reliability of radio-
graphic femoral neck fracture by using a checklist based
scoring approach.19-23 The purpose of this scoring based
2350
system is to improve femoral neck fracture nonunion
agreement between radiologist and orthopedic surgeons.
The radiographic union score for the hip evaluates for
each cortex of the femur in the setting of fracture with a
score of 1 (callus absent, fracture line visible), 2 (callus
present, fracture line visible), or 3 (callus present, frac-
ture line invisible) to determine nonunion. Patients with
a score of 3 for each cortex indicate maximum healing
and complete union. RUSH scores have been shown to
have 100% positive predictive value for defining radio-
graphic nonunion at 6 months postinjury.20 This is
important because RUSH has the potential for predicting
reoperation for nonunion. In our study, a similar 1–3
classification system was used, but given the small size of
the bone evaluated and the fact Panorex does not allow
for visualization lingual and buccal cortices, a single
score was given for the graft/graft and graft/native bone
interfaces. The limitation to using a radiographic union
score of the mandible is that this scoring system has not
been validated as there may be a discrepancy between
surgeons' assessment and radiographic assessment. We
recognize that a radiographic finding of nonunion may
not ultimately translate into a clinical problem. However,
we also recognize that patients will develop plate frac-
tures years after surgery, and that once this occurs it
likely places the patient at higher risk for developing
pain, plate infection, osteoradionecrosis, and other
sequelae. This is likely a consequence of micromotion at
nonunion, and plate fatigue. These secondary and ter-
tiary events are significant and morbid to the patients
that experience them, but would be difficult in this popu-
lation to demonstrate a correlation.
Many studies have shown a significant reduction in
operative and ischemia time using stereolithic models and
VSP.4,6-8,23-28 Similar to those studies, we found a signifi-
cant reduction in operative and reconstruction time in
patients undergoing 3D/VSP. The use of 3D models allows
the surgeon to better plan the resection, anticipate and
visualize the defect, and contour soft tissue and bony com-
ponents of the flap to the defect on the model prior to flap
inset in the patient.29 This decreased operative and recon-
structive time could lead to less anesthetic time, surgeon
fatigue, and fewer complications. At our institution, a pre-
vious survey of 10 head and neck surgeons illustrated that
3D/VSP improved inoperative efficiency, accuracy, and
precision.29 The accuracy of 3D printed cutting guides,
stereolithic models, and customizable mandibular plates
allows a complex procedure to be less surgeon dependent
and allows advanced computer software to help determine
appropriate cutting angles in the fibula bone to improve
bone-to-bone contact which can potentially lower compli-
cations and increase bony union. Our study did not use
custom plates for reconstruction, but custom
MAY ET AL.
reconstruction plates have the potential for improving
accuracy of and biomechanical properties of the recon-
struction plate.30 This may be useful in patients with com-
plex anatomy or pathology. A limitation of custom
reconstruction plate is the potential change of the extent
of resection. This may alter the osteotomy site and there-
fore render a custom fit plate non-functional. Blanc et al
compared cephalometric measurements and 3D analysis
of patients who underwent VSP to postoperative facial
bone scans at 6 months. The study found no significant
difference in preoperative VSP compared to postoperative
facial scans.25 Moreover; a pool quantitative analysis dem-
onstrated significant improvement in orthognathic mea-
sures of accuracy using 3D/VSP.24
The number of osteotomy sites or fibular segments
could suggest an increase in reconstruction complexity.26
Toto et al compared the number of fibular free flap neo-
mandibular osteotomy sites between stereolithic models,
in situ osteotomies, and preoperative planning with oste-
otomy guides, and the authors did not find a significant
difference in outcomes or complications among the three
groups.26 Our study compared the number segments as a
complexity of reconstruction, which did not show any
significant difference outcomes of bony union across
treatment groups. Our prediction that there would be
greater complexity in the 3D/VSP group, as we are more
likely to add a segment to improve mandibular aesthetics,
was not reflected in our analysis.
We found a significant difference in free flap compli-
cations between the two methods of reconstruction with
the most common complication being infection, followed
by partial flap necrosis and fistula formation. Several
patients had more than one free flap complication
in the CM group. The significant difference in complica-
tion rates between methods of reconstruction may dem-
onstrate the complex methodological heterogeneity of
reporting free flap complications. In a recent meta-
analysis and systemic review, flap loss, fistula, and infec-
tion were not significantly different between reconstruc-
tion methods.24 In our study, we performed a subgroup
analysis of complication outcomes based upon complica-
tion site. Plate fracture was low in both groups; however,
plate removal trended toward significance. The difference
in mandibular plate removal between CM and 3D/VSP is
likely multifactorial with improvements in surgical tech-
nique, plate screw placement, and improvement in qual-
ity and design of titanium hardware that may have
occurred over the years. Although we did not find signifi-
cant differences in mandible fracture, plate fracture, or
donor site complications, the composite outcome event in
Table 3 reached significance between CM and 3D/VSP.
This composite outcome event may be due to low compli-
cation rates in these respectively categories but a
MAY ET AL.
compilation of events may have provided power for sig-
nificance. In addition, we did not find a difference in
indications for surgery between the two treatment groups
but indications for surgery such as osteoradionecrosis or
primary tumor followed by radiation could lead to a
selection bias and contribute to free flap complications.
Since we are comparing two different eras, era effects
may provide a limitation to the complication differences
seen between the two treatment groups. Improvements over
time in surgical techniques may unfairly benefit procedures
implemented later in the study timeframe, in this case the
3D/VSP. Surgeon experience may contribute to a modifica-
tion of techniques that may not be readily apparent in a ret-
rospective review. In the early adaptation of 3D/VSP,
selection bias may have occurred by choosing patients who
might have more favorable anatomy and pathology to be a
candidate for 3D/VSP. In our era analysis, we included the
timeframe from the years 2000–2018, as there was no period
of a strong overlap of the two procedures to allow a direct
comparison. Ultimately, considering the year effect as a
proxy for experience and refinement of technique, we pre-
dict that experience would also help 3D/VSP as well as
CM. When we control for the year, the effects are still recog-
nizably different between the two groups. Surgical tech-
niques and improvements over time do not seem to be
strong enough to outweigh the differences between bony
union and complications in the two groups.
Our study has several limitations. This is a retrospec-
tive review of two separate cohorts of patients in two sepa-
rate time periods, where the use of 3D/VSP was adapted
in our practice starting in 2016. The 3D/VSP cohort sam-
ple size of 28 is much smaller than the 232 sample size of
the conventional method cohort. This small sample size is
a limitation of this study and has the potential for a reduc-
tion in power of the study and increased margin of error.
The comparison of a historical control group, conventional
methods, subjects the study for the potential of era effects.
Nonetheless, era effects analysis continued to demonstrate
a significant difference in radiographic bony union and
complications between the two groups. To evaluate bony
union, a radiologist was blinded to each reconstruction
method; however, the time points to bone scans in each
patient was not standardized as this was a retrospective
review and a combination of CT, PET/CT, and Panorex
were evaluated. Nonetheless, scans were selected closest to
the 1 and 2 year intervals of follow-up to provide consis-
tency between each cohort of patients. Imaging studies
that were several months off from these time points do
allow for time to event analysis where we found time to
bony union to be significantly improved using 3D/VSP.
The use of 3D/VSP incurs significant costs; however, these
costs may be offset by a reduction in operative time.26,31 In
our institution, VSP and 3D printed models is performed
2351
on site with an ease of team interaction between surgeons,
radiologists, and engineers.
5 | CONCLUSION
In summary, 3D anatomic model printing and VSP
reduces the rate of nonunion, operative time, and flap-
related complications in patients undergoing FFF recon-
struction for mandibular defects when compared to free
hand contouring. When conglomerated, there was a major
improvement in postoperative complications and long-
term mandible-related outcomes. This demonstrates that
3D modeling and VSP not only improves intraoperative
management, but also has long-term benefits.
ACKNOWLEDGMENTS
We would like to thank the entire Department of
Otorhinolaryngology-Head and Neck Surgery, anatomi-
cal modeling lab, Department of Radiology for their con-
tinued support for this project and dedication to patient
care. This study was supported by Internal departmental
funding for statistical analysis.
CONFLICT OF INTEREST
The authors declare no potential conflict of interest.
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are avail-
able from the corresponding author upon reasonable
request.
ORCID
Matthew M. May https://orcid.org/0000-0002-6425-
6991
Eric J. Moore https://orcid.org/0000-0003-1103-6212
Kathryn M. Van Abel https://orcid.org/0000-0003-0513-
4203
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How to cite this article: May MM, Howe BM,
O'Byrne TJ, et al. Short and long-term outcomes of
three-dimensional printed surgical guides and
virtual surgical planning versus conventional
methods for fibula free flap reconstruction of the
mandible: Decreased nonunion and complication
rates. Head & Neck. 2021;43:2342–2352. https://doi.
org/10.1002/hed.26688