- Email: [email protected]
Outcomes of microvascular free flap reconstruction for mandibular osteoradionecrosis: A systematic review
Accepted Manuscript Outcomes of Microvascular Free Flap Reconstruction for Mandibular Osteoradionecrosis: A Systematic Review Migie Lee, Ronald Y. Chin, Guy Eslick, Niranjan Sritharan, Suchitra Paramaesvaran PII:
S1010-5182(15)00058-X
DOI:
10.1016/j.jcms.2015.03.006
Reference:
YJCMS 1989
To appear in:
Journal of Cranio-Maxillo-Facial Surgery
Received Date: 12 December 2014 Revised Date:
2 March 2015
Accepted Date: 3 March 2015
Please cite this article as: Lee M, Chin RY, Eslick G, Sritharan N, Paramaesvaran S, Outcomes of Microvascular Free Flap Reconstruction for Mandibular Osteoradionecrosis: A Systematic Review, Journal of Cranio-Maxillofacial Surgery (2015), doi: 10.1016/j.jcms.2015.03.006. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Title: Outcomes of Microvascular Free Flap Reconstruction for Mandibular Osteoradionecrosis: A Systematic Review.
Keywords: Osteoradionecrosis, Mandible, Free Tissue Flaps, Surgical Flaps, Head
Authors: Migie Lee1 Ronald Y Chin2 Guy Eslick3 Niranjan Sritharan1
Affiliations:
M AN U
Suchitra Paramaesvaran2
SC
RI PT
and Neck Neoplasms
1
Department of Otolaryngology, Head and Neck Surgery, Nepean Hospital, Sydney
2
University of Sydney, Australia
3
The Whiteley-Martin Research Centre, The University of Sydney, Nepean Hospital,
TE D
Sydney
Corresponding author: Ronald Y Chin
AC C
EP
Address: Department of Otolaryngology, Head and Neck Surgery, Nepean Hospital Derby Street, Penrith NSW 2750 Email: [email protected]
ACCEPTED MANUSCRIPT
ABSTRACT Introduction Osteoradionecrosis of the mandible is a devastating complication of radiotherapy in patients with head and neck cancer. Many cases present at a late stage, from months
RI PT
to years following completion of radiation therapy. When medical treatment fails, surgery may be required with a variety of free flaps available for microvascular reconstructive techniques.
Objective
SC
To conduct a systematic review of the literature investigating the outcomes of free flap reconstruction of the jaw in mandibular osteoradionecrosis and determine the
M AN U
failure rates of different flap tissue.
Methods
A systematic literature search was performed using Medline (Ovid) Pubmed and Embase databases and Google Scholar. Primary outcome measures were flap failures and complications, with donor site complications representing the secondary outcome
Results
TE D
measure. Analysis of pooled outcomes was undertaken for different flaps.
333 articles were identified and 15 articles met the final inclusion criteria, detailing 368 primary free tissue flap transfers. There was a flap failure rate of 9.8%. There
EP
were 146 post-operative complications (39.7%), the most common being fistula
AC C
formation (8.4%), hardware plate exposure (7.1%) and flap wound infections (6.5%).
Conclusion
The fibula is the workhorse free flap for reconstruction in mandibular osteoradionecrosis. Evidence to date is largely limited with the need for larger powered multi-institutional prospective studies to determine the ideal flap donor tissue and evaluate patient and treatment predictors of free flap outcomes in order to tailor the best patient-based surgical approach for mandibular osteoradionecrosis.
ACCEPTED MANUSCRIPT
INTRODUCTION Osteoradionecrosis (ORN) is one of the most debilitating complications of radiation therapy in patients undergoing treatment for head and neck cancer. It is defined as exposed irradiated bone that fails to heal over a three-month period in the absence of
RI PT
residual or recurrent tumour (Epstein, Wong et al. 1987) and can affect any bony component of the craniomaxillofacial skeleton (Teng and Futran 2005).
The management of ORN comprises primarily on symptomatic management
and prevention of further disease progression. Despite appropriate management, many patients will progress to advanced ORN disease to a stage where tissue may become
SC
necrotic and overhwlemed by infection, making it difficult to salvage affected bone (Alam, Nuara et al. 2009).
With advancements in reconstructive techniques, there is increasing evidence
M AN U
for improved outcomes with microvascular free flap (MVFF) transfer following segmental resection of non-viable bone in osteoradionecrosis. MVFF in reconstructing ORN defects has an advantage over multi-stage reconstructions as it allows simultaneous reconstruction of both hard and soft tissue components of the defect with tissue from a separate site (Buchbinder and St Hilaire 2006).
Historically, it has been shown that higher complication rates are experienced when reconstructing tissue previously exposed to radiation treatment (Weaver and
TE D
Smith 1973, Margolis, Smith et al. 1976, Salyer, Newsom et al. 1977, Kudo and Fujioka 1978, Adamo and Szal 1979, Serafin, Riefkohl et al. 1980) with the key challenge in the inherent poor wound healing in irradiated tissue. Radiation exposure compromises the integrity of recipient vessels and negatively affects free flap viability (Krag, Holck et
EP
al. 1982), with both pre-operative and post-operative radiotherapy associated with an increased flap complication rate (Deutsch, Kroll et al. 1999). With advancements in technology and surgical techniques, the rates of flap success
AC C
have increased to a reported rate of 86-100% (Celik, Wei et al. 2002, Store, Boysen et al. 2002, Ang, Black et al. 2003, Militsakh, Wallace et al. 2005, Buchbinder and St Hilaire 2006). Whilst free flap outcome is arguably primarily due to surgical technique, a better understanding of clinical predictors and contributing factors is necessary to help optimise peri-operative and post-operative management. The aim of this systematic review is to present collective evidence from up to date literature and further define factors contributing the flap failure by exploring the outcomes of microvascular free tissue transfer reconstructions in patients with mandibular osteoradionecrosis.
ACCEPTED MANUSCRIPT
METHODS
Study Protocol We followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses
RI PT
(PRISMA) guidelines (Moher, Liberati et al. 2009). Relevant articles were identified
through a systematic search of the databases MEDLINE, PubMed, Embase, Cochrane
databases and Google Scholar through to September 1, 2014. The search used the terms ‘Free Tissue Flaps’ AND ‘Osteoradionecrosis’ OR ‘Osteoradionecrosis’ AND ‘Mandibular Reconstruction’, which were searched as text word and as exploded
SC
medical subject headings where possible. The reference lists of relevant articles were
also hand-searched for appropriate studies. Conference proceedings were not examined. No language restrictions were used in either the search or study selection.
M AN U
A search for unpublished literature was not performed.
Study Selection
We included all types of studies that met the following inclusion criteria: (1) Osteoradionecrosis was clearly described by clinical examination and/or confirmed radiologically; (2) the total sample size of the study exceeded 5 free flaps; (3) results examined the outcomes of microvascular free tissue transfer reconstruction; (4) the
TE D
point estimate was reported as an odds ratio (OR), or the data was presented such that an OR could be calculated; (5) the 95% confidence interval (CI) was reported, or the data was presented such that the CI could be calculated. Two independent reviewers initially screened the titles and abstracts of the search for possible inclusion and the full
EP
text of all screened studies were obtained for assessment. Any uncertainty or disagreement was resolved by discussion with a third independent reviewer. We
AC C
excluded studies that did not meet the inclusion criteria.
Data Extraction
One reviewer (M.L.) performed the data extraction using a standardized data extraction form. Information was extracted on the publication year, study design, number of cases, population type, country, continent, mean age, gender, adjuvant treatment, months of follow-up, flap failure rates and incidence of free flap complications. Quality of the studies was not assessed as all studies found were observational case series. In articles that provided a contact email address, authors were contacted for missing data.
ACCEPTED MANUSCRIPT
Figure 1. Study selection flowchart
RI PT
From the initial literature search, 333 titles were retrieved and after removal of
duplicates, screening and exclusion based on criteria, a final 15 articles met the final
inclusion criteria (Ioannides, Fossion et al. 1994, Nakatsuka, Harii et al. 1996, Curi and Dib 1997, Santamaria, Wei et al. 1998, Chang, Oh et al. 2001, Celik, Wei et al. 2002, Store, Boysen et al. 2002, Militsakh, Wallace et al. 2005, Bozec, Poissonnet et al.
SC
2006, Suh, Blackwell et al. 2010, Baumann, Yu et al. 2011, Cannady, Dean et al. 2011, Chandarana, Chanowski et al. 2013, Sawhney and Ducic 2013, Hillerup, Elberg et al.
M AN U
2014).
Statistical Analysis
Pooled odds ratio estimates and 95% confidence intervals were calculated for risk factors of mandibular osteoradionecrosis using a random effects model (DerSimonian and Laird 1986). We tested heterogeneity with Cochran’s Q statistic, with P<0.10
TE D
indicating heterogeneity, and quantified the degree of heterogeneity using the I2 statistic, which represents the percentage of the total variability across studies which is due to heterogeneity that is not due to chance (Higgins, Thompson et al. 2003). All
AC C
EP
analyses were performed with Comprehensive Meta-analysis (version 2.0).
ACCEPTED MANUSCRIPT
RESULTS Study Characteristics
RI PT
Table 1 shows selected characteristics of the identified studies (Ioannides, Fossion et al. 1994, Nakatsuka, Harii et al. 1996, Curi and Dib 1997, Santamaria, Wei et al. 1998, Chang, Oh et al. 2001, Celik, Wei et al. 2002, Store, Boysen et al. 2002, Militsakh, Wallace et al. 2005, Bozec, Poissonnet et al. 2006, Suh, Blackwell et al. 2010,
Baumann, Yu et al. 2011, Cannady, Dean et al. 2011, Chandarana, Chanowski et al.
SC
2013, Sawhney and Ducic 2013, Hillerup, Elberg et al. 2014). Eight studies examined populations from North America, one from South America, four from Europe and two
from Asia. Of the 11 studies that reported follow-up periods, the average duration was
M AN U
35.4 months. Mean age was 57.4 years, and the reported percentage of males was 68% (58%-72%), I2=37.52, p=0.07 and smokers 55% (18%-88%), I2=92.07, p<0.001. Squamous cell carcinoma comprised the majority of cases, 83% (77%-89%), I2=0.00, p=0.61 and the mean radiotherapy dose 67.71 gray (Gy). Adjuvant Treatment
Of those that reported adjuvant treatment, one quarter received adjuvant
TE D
chemotherapy (25%(17%-36%), I2=37.63, p=0.16) and more than half underwent hyperbaric oxygen therapy (HBO) (53%(40%-65%), I2=70.83, p<0.01.
EP
Table 1. Study characteristics
AC C
Table 2. Free Flap Failures
ACCEPTED MANUSCRIPT
Free Flap Donor Sites A total of 368 primary free flaps were performed in 15 different studies. Used donor sites comprised of that from the fibula (n= 215), iliac crest (n=43), radial (n=31),
(n=12), serratus anterior (n=10) and the humerus (n=5).
Flap Failures
RI PT
scapula (n=18), anterolateral thigh (n=18), latissimus dorsi (n=16), rectus abdominis
There were 36 flap failures (9.8% (9%-16%), I2=0.00, p=0.56) requiring revision
SC
operations. These flaps originated from donor sites fibula (n=10), iliac crest (n=7),
scapula (n=2) and anterolateral thigh (n=1) and latissimus dorsi (n=1). In the 15 failures unaccounted for (from 4 studies), donor sites were not stated. Of those that failed, 5
M AN U
had fistula formation, 3 became otherwise infected, 10 had vessel thromboses and 2 had skin paddle necrosis. One case had carotid artery rupture in which the flap that was connected to the vessels in the contralateral neck was lost during resuscitation. This patient subsequently died from multiorgan failure.
AC C
EP
TE D
Figure 2. Forest plot for flap failure event rate per study
ACCEPTED MANUSCRIPT
The pooled event rate for patients who underwent free flap reconstruction for mandibular osteoradionecrosis is 0.12 (95%CI 0.09-0.16). Failure rates according to tissue type were: iliac crest (n=7, 16.3%), scapula (n=2,
RI PT
11.1%) and anterolateral thigh (n=1, 5.6%) and fibula (n=10, 4.7%),
Other Flap Complications
There were 146 post-operative complications (39.7%) that otherwise did not result in
SC
flap failure. The most common complications fistula formation (n=31), hardware plate
exposure (n=26) and flap wound infections (n=24). Vessel complications were noted in a total 5 patients; thromboses were seen in 16 free flaps (4.3%), haematoma formation
M AN U
in 5 (1.4%) and 2 patients (0.5%) had carotid artery rupture following flap reconstruction.
Table 3. Free Flap Complications
DISCUSSION
TE D
A total of 20 (5.4%) donor site complications were reported.
Osteonecrosis is a serious complication not limited to the effects of radiotherapy but
EP
also medication-induced side effects e.g. bisphosphonates (Vercruysse, Backer et al.
2014). When it does arise, it can cause significant morbidity particularly that is devastating to the patient. The focus of this review is mandibular osteoradionecrosis in
AC C
head and neck cancer patients, which has variable incidence rates reported in the literature, ranging from as low as 0.4% to as high as 56% (Jereczek-Fossa and Orecchia 2002). In advanced disease, paradigm shifts in the management of mandibular osteoradionecrosis have seen surgical resection and immediate free tissue transfer performed for stage 3 disease (Jacobson, Buchbinder et al. 2010). Free flap reconstruction in the irradiated jaw is difficult. Choosing the right donor site and harvesting an appropriate flap requires great precision and skill. Identification and dissection of recipient vessels can be arduous and necessitates selection of vessels
ACCEPTED MANUSCRIPT
arising from outside the irradiated field, often from the contralateral neck (Cordeiro, Disa et al. 1999, Ang, Black et al. 2003). Surgical reconstruction of the mandible in patients with osteoradionecrosis is reserved for advanced disease. In the treatment of early disease, the authors
RI PT
recommend oral hygiene, optimization of nutritional status and multidisciplinary
management including dental, head and neck surgery and plastics surgery review. In cases that are more severe, debridement of necrotic tissue and appropriate use of antibiotics with involvement of infectious diseases are necessary.
In treatment early stage disease, management is conservative comprising of
SC
debridement of necrotic tissue, antibiotics and in some institutions, hyperbaric oxygen therapy (HBO). From the 1960s, HBO had been utilised as an additional treatment modality in the management of osteoradionecrosis, popularized by Marx (Marx and
M AN U
Ames 1982) as an adjunct to soft tissue flaps in managing irradiated tissue. It continues to be utilized by some institutions and although in the days of its inception, HBO did show promising results in the treatment of ORN (Mainous, Hart et al. 1975, Hart and Mainous 1976, Davis, Dunn et al. 1979), current literature demonstrates no benefit. Recent evidence has questioned any significant benefit (Mounsey, Brown et al. 1993, Maier, Gaggl et al. 2000) with a multicenter randomized, double-blinded, placebo-controlled trial in 2004 showing no benefit of HBO treatment in patients for
TE D
osteoradionecrosis of the jaw (Annane, Depondt et al. 2004). Reconstructive procedures should be reserved for difficult and severe cases where conservative management has been unsuccessful in achieving adequate healing. Surgical repair of osteoradionecrotic tissue is a challenge both peri-operatively
EP
and post-operatively. Previous surgery obliterates tissue planes and radiation-induced tissue breakdown leads to problems with wound healing(Ang, Black et al. 2003). Local wound healing problems may manifest as infection, dehiscence, fistula formation
AC C
and/or plate exposure and rates of such complications range from 8 to 43% (Celik, Wei et al. 2002, Coskunfirat, Wei et al. 2005), the upper limit close to that of this review (42.7%). Progression of local wound complications, or other microvascular events e.g. thrombosis, can lead to partial or total free flap loss requiring further surgery for a second free flap or regional myocutaneous flap (Ang, Black et al. 2003). The overall flap failure rate was 9.8% (n=36). Flap tissue type was identified in
21 flaps across 11 studies. 4 of the 15 studies did not identify the types of flaps that failed, leaving 15 flap failures unaccounted for.
ACCEPTED MANUSCRIPT
In mandibular reconstruction, restoration of bone continuity is not the only key to success. The surgery needs to achieve adequate bone height and width and supporting of overlying soft tissue structures to restore jaw motion (McAllister and Haghighat 2007). The masseter muscle is the strongest muscle in the body and does
RI PT
not stretch uniformly for major jaw movement thus a good supportive bone and soft
tissue structural graft is crucial to maintain the functional integrity of the jaw. The soft tissue needs to be forgiving in both size as quality thus when considering the use of non-vascularised bone grafts, the ideal tissue should have enough bulk, vascularity and cellularity to achieve good graft application (Arotiba, Effiom et al. 2012).
SC
Four osteocutaneous flaps are commonly used for mandible reconstruction:
fibula flap, iliac crest flap, scapula flap and the radial flap. Li et al (Li, Jung et al. 2012)
M AN U
conducted a cohort study in which 116 patients underwent latissimus dorsi free flap and plate reconstruction following advanced oro-mandibular tumour resection. The series demonstrated a very good survival rate (99.1%). Despite favourable results, the use of latissimus dorsi along with serratus anterior and upper arm (humerus) flaps is becomingling increasingly less common, largely due to the limited available bone to repair mandible defects, and the short pedicle available, which make the flaps difficult to anastomose.
TE D
The iliac crest flap is usually considered when there is a contraindication to the fibula flap. Patients with signs of lower limb vascular insufficiency or a history of lower limb fracture are deemed unsuitable for the fibula flap. It does offer certain unique advantages over the fibula flap in the quality and quantity of bone available, whereby
EP
the resting shape of the iliac crest bone resembles the mandible anatomically, requiring minimal osteotomy. The major drawback is that whilst it has robust blood supply to the bone and internal oblique muscle, issues can arise in the blood supply to the skin,
AC C
whereby the supplying perforators of the deep circumflex iliac artery can tear easily as they pass through the layers of the abdominal wall (Chepeha 2001). The iliac crest flap had a success rate of 76.6%, with the most common failure reason attributed to venous thrombosis (Ioannides, Fossion et al. 1994). The scapula flap is a reasonable option with its main feature being that of its
abundant soft tissue and its two discrete skin paddles, which allows for greater flexibility in repairing complex facial defects. A recent retrospective institutional study found the free scapula/parascapular flap to be a versatile and reliable flap for head and neck reconstructions with a good success rate (96%) and a low complication rate (2.3%) (Mitsimponas, Iliopoulos et al. 2014). One limitation of this flap is its limited
ACCEPTED MANUSCRIPT
length, and the thin and fine nature of the bone. Another disadvantage is the need for patient repositioning during the surgery in order to harvest the flap, precluding simultaneous harvesting at the time of tumour resection and prolonging the operating time (Miles, Goldstein et al. 2010).
RI PT
The radial forearm free flap is a reasonable alternative in its key property of superior blood supply compared to other tissue options. It offers a large, thin and pliable skin segment that is widely favored for soft tissue reconstruction of
pharyngoesophageal defects as a fasciocutaneous flap. Additional bulk can be
included with use of the brachioradialis muscle and it has good nerve supply for
SC
optimal recovery of sensory function (Disa and Cordeiro 2000). As an osteocutaneous flap however, the radius in limited in the lack of bone available for osteotomy (AbdelKader, Tamam et al.). There is approximately 10cm of bone available to be taken and
M AN U
although it is cortical bone, only one third of the cross-sectional area can be taken without increasing the risk of mechanical stress fracture (Clark, Greenwood et al. 2004). This compromises the thickness of the bone and thus only a small bony defect can be repaired using the radial flap, unless combined with other donor sites (Rinaldo, Shaha et al. 2002). Of the total 31 radial free flaps, no flap failures were reported. However, it is unclear whether those undertaken in the studies included osteotomy or if they were fasciocutaneous flaps only.
TE D
The fibula microvascular free flap for head and neck reconstruction was first introduced by Hidalgo in 1989(Hidalgo 1989) and is now considered as the workhorse for mandible reconstruction (George and Krishnamurthy 2013, Succo, Berrone et al. 2014) (Ang, Black et al. 2003). The fibula osteocutaneous free flap has quickly gained
EP
popularity over other vascularized bone flaps in recent years for several reasons. The fibula benefits from its quality of bone, with good cortical thickness, and the generous length of bone available (up to 25-30cm), which permits multiple osteotomies even
AC C
whilst the pedicle is still attached (Urken, Buchbinder et al. 1991) (Hao, Chen et al. 1999). The vasculature is also ideal. The flap’s dominant arterial supply is from the peroneal artery and venous drainage via the 2 venae comitantes, which have an average caliber of 1.5mm and 3mm respectively. These vessel diameters closely match that of most recipient vessels in the neck facilitating effective anastomoses. Its long and reliable vascular pedicle (up to 12-15cm) is useful when confronted with recipient vessels that are difficult to locate in heavily irradiated tissue (Wallace, Chang et al. 2010). Furthermore, the fibula provides the bony platform for eventual prosthetic rehabilitation, allowing the placement of intraosseous dental implants. The fibula free
ACCEPTED MANUSCRIPT
flap offers considerable advantages over its counterparts as the ideal flap of choice for mandibular reconstruction and it was by far the most common free flap tissue used (n=215) and, from the free flap failure data reported, had a good success rate (95.3%). With the great variations across the studies, and the small numbers of some
flap site were unable to be conducted.
RI PT
e.g. humerus (n=5) sufficiently powered subset analyses to determine the best donor
The purpose of this systematic review was to summarize the reported literature to date in the variety of free flap reconstructions used and the outcomes of different
practice across different institutions. We appreciate that this review is a retrospective
SC
pooling of case series predisposed to the drawbacks associated with such studies. We also acknowledge the assumed limitations in the outdated nature of some articles, particularly those predating the new millennium (Ioannides, Fossion et al. 1994, Curi
M AN U
and Dib 1997, Santamaria, Wei et al. 1998), with which current practice may now vastly differ to that carried out in the older studies. In the 15 studies included in this review, all retrospective case series, there were a total 368 primary microvascular free flaps studied with a 9.8% failure rate. Flap failure requires a revision operation and in most instances, necessitates a secondary free flap from another donor site. This leads to further morbidity and a longer hospital stay, which calls for measures in acquiring a better understanding of the factors associated with flap loss. Direct associations
TE D
between clinical and patient factors with flap loss overall were not explored in the included articles in this systematic review, thus pooled outcomes of such could not be reported. In the literature, important factors that have been associated with graft survival include the length of mandibular defect, timing of the reconstruction
EP
(immediate or delayed), cancer diagnosis, intraoral communication, estimated blood loss and the duration of post-operative antibiotics (August, Tompach et al. 2000). Furthermore, longer close follow-up periods are needed. All of the 11 studies that
AC C
reported follow-up period durations reported outcomes within a 5 year post-operative period. Long-term outcomes and potential adverse consequences are not known. This is the first systematic review looking at the surgical outcomes of
reconstruction with microvascular free flaps used in patients with mandibular osteoradionecrosis. The results show the challenges inherent in successful microvascular free flap reconstruction in patients with mandibular osteoradionecrosis, however the systematic review is limited in the retrospective nature of all studies and the inherent selection bias in the patient populations. The lack of randomized trials, variability in the donor flap site used and the potential for confounding factors e.g.
ACCEPTED MANUSCRIPT
adjuvant medical treatment and surgical technique, limit an objective analysis. As institutional practices in relation to flap choice and surgical technique and consistencies in follow-up reporting of outcomes are likely to vary, future prospective studies with indepth analyses of the predictors of flap survival are needed. Recommendations for
RI PT
future research directions include the investigation of predictive patient and clinical factors and determination of the ideal donor flap site associated with the best outcomes.
CONCLUSIONS
SC
Osteoradionecrosis of the mandible is an uncommon but significant complication of
radiotherapy, where surgical treatment for advanced disease can carry great morbidity with post-operative complications. Whilst a number of free flap tissue types can be
M AN U
used, the fibula free flap continues to be the gold standard and workhorse flap in the reconstruction of mandibular defects with a good success rate. Higher-powered prospective studies that closely examine patient and clinical factors associated with flap outcomes will lead to greater understanding of predictors of flap survival and help guide individualized patient approaches to appropriate microvascular reconstruction in mandibular osteoradionecrosis.
AC C
EP
TE D
Conflicts of Interest: None.
ACCEPTED MANUSCRIPT
REFERENCES
AC C
EP
TE D
M AN U
SC
RI PT
Abdel-Kader, M. S., A. A. Tamam, A. A. Elderwy, M. Gad, M. A. El-Gamal, A. Kurkar and A. S. Safwat (2013). "Management of symptomatic ureteral calculi during pregnancy: Experience of 23 cases." Urol Ann 5(4): 241-244. Adamo, A. K. and R. L. Szal (1979). "Timing, results, and complications of mandibular reconstructive surgery: report of 32 cases." J Oral Surg 37(10): 755763. Alam, D. S., M. Nuara and J. Christian (2009). "Analysis of outcomes of vascularized flap reconstruction in patients with advanced mandibular osteoradionecrosis." Otolaryngol Head Neck Surg 141(2): 196-201. Ang, E., C. Black, J. Irish, D. H. Brown, P. Gullane, B. O'Sullivan and P. C. Neligan (2003). "Reconstructive options in the treatment of osteoradionecrosis of the craniomaxillofacial skeleton." Br J Plast Surg 56(2): 92-99. Annane, D., J. Depondt, P. Aubert, M. Villart, P. Gehanno, P. Gajdos and S. Chevret (2004). "Hyperbaric oxygen therapy for radionecrosis of the jaw: a randomized, placebo-controlled, double-blind trial from the ORN96 study group." J Clin Oncol 22(24): 4893-4900. Arotiba, G. T., A. O. Effiom, A. S. Ayodele, M. O. Ogundana, M. O. Gbotolorun, H. O. Olasoji, O. James, A. L. Ladeinde, V. I. Ugboko, K. C. Ndukwe, I. C. Ikem and R. O. Braimah (2012). "A classification system for recurrent ameloblastoma of the jaws-review of 30 cases in Nigerians." Nig Q J Hosp Med 22(1): 44-51. August, M., P. Tompach, Y. Chang and L. Kaban (2000). "Factors influencing the long-term outcome of mandibular reconstruction." J Oral Maxillofac Surg 58(7): 731-737; discussion 738. Baumann, D. P., P. Yu, M. M. Hanasono and R. J. Skoracki (2011). "Free flap reconstruction of osteoradionecrosis of the mandible: a 10-year review and defect classification." Head Neck 33(6): 800-807. Bozec, A., G. Poissonnet, S. Converset, J. Vallicioni, F. Demard and O. Dassonville (2006). "[Fibula free flap for reconstruction of extensive mandibular osteoradionecrosis]." Ann Otolaryngol Chir Cervicofac 123(2): 98-106. Buchbinder, D. and H. St Hilaire (2006). "The use of free tissue transfer in advanced osteoradionecrosis of the mandible." J Oral Maxillofac Surg 64(6): 961964. Cannady, S. B., N. Dean, A. Kroeker, T. A. Albert, E. L. Rosenthal and M. K. Wax (2011). "Free flap reconstruction for osteoradionecrosis of the jaws--outcomes and predictive factors for success." Head Neck 33(3): 424-428. Celik, N., F. C. Wei, H. C. Chen, M. H. Cheng, W. C. Huang, F. C. Tsai and Y. C. Chen (2002). "Osteoradionecrosis of the mandible after oromandibular cancer surgery." Plast Reconstr Surg 109(6): 1875-1881. Chandarana, S. P., E. J. Chanowski, K. A. Casper, G. T. Wolf, C. R. Bradford, F. P. Worden, A. Eisbruch and D. B. Chepeha (2013). "Osteocutaneous free tissue transplantation for mandibular osteoradionecrosis." J Reconstr Microsurg 29(1): 5-14. Chang, D. W., H. K. Oh, G. L. Robb and M. J. Miller (2001). "Management of advanced mandibular osteoradionecrosis with free flap reconstruction." Head Neck 23(10): 830-835.
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
Chepeha, D. B., Teknos, T.N., Ed. (2001). Microvascular Free Flaps in Head and Neck Reconstruction, Lippincott Williams & Wilkins. Clark, S., M. Greenwood, R. J. Banks and R. Parker (2004). "Fracture of the radial donor site after composite free flap harvest: a ten-year review." Surgeon 2(5): 281286. Cordeiro, P. G., J. J. Disa, D. A. Hidalgo and Q. Y. Hu (1999). "Reconstruction of the mandible with osseous free flaps: a 10-year experience with 150 consecutive patients." Plast Reconstr Surg 104(5): 1314-1320. Coskunfirat, O. K., F. C. Wei, W. C. Huang, M. H. Cheng, W. G. Yang and Y. M. Chang (2005). "Microvascular free tissue transfer for treatment of osteoradionecrosis of the maxilla." Plast Reconstr Surg 115(1): 54-60. Curi, M. M. and L. L. Dib (1997). "Osteoradionecrosis of the jaws: a retrospective study of the background factors and treatment in 104 cases." J Oral Maxillofac Surg 55(6): 540-544; discussion 545-546. Davis, J. C., J. M. Dunn, G. A. Gates and R. D. Heimbach (1979). "Hyperbaric oxygen. A new adjunct in the management of radiation necrosis." Arch Otolaryngol 105(2): 58-61. DerSimonian, R. and N. Laird (1986). "Meta-analysis in clinical trials." Control Clin Trials 7(3): 177-188. Deutsch, M., S. S. Kroll, N. Ainsle and B. Wang (1999). "Influence of radiation on late complications in patients with free fibular flaps for mandibular reconstruction." Ann Plast Surg 42(6): 662-664. Disa, J. J. and P. G. Cordeiro (2000). "Mandible reconstruction with microvascular surgery." Semin Surg Oncol 19(3): 226-234. Epstein, J. B., F. L. Wong and P. Stevenson-Moore (1987). "Osteoradionecrosis: clinical experience and a proposal for classification." J Oral Maxillofac Surg 45(2): 104-110. George, R. K. and A. Krishnamurthy (2013). "Microsurgical free flaps: Controversies in maxillofacial reconstruction." Ann Maxillofac Surg 3(1): 72-79. Hao, S. P., H. C. Chen, F. C. Wei, C. Y. Chen, A. R. Yeh and J. L. Su (1999). "Systematic management of osteoradionecrosis in the head and neck." Laryngoscope 109(8): 1324-1327; discussion 1327-1328. Hart, G. B. and E. G. Mainous (1976). "The treatment of radiation necrosis with hyperbaric oxygen (OHP)." Cancer 37(6): 2580-2585. Hidalgo, D. A. (1989). "Fibula free flap: a new method of mandible reconstruction." Plast Reconstr Surg 84(1): 71-79. Higgins, J. P., S. G. Thompson, J. J. Deeks and D. G. Altman (2003). "Measuring inconsistency in meta-analyses." BMJ 327(7414): 557-560. Hillerup, S., J. J. Elberg, J. J. Thorn and M. Andersen (2014). "Reconstruction of irradiated mandible after segmental resection of osteoradionecrosis-a technique employing a microvascular latissimus dorsi flap and subsequent particulate iliac bone grafting." Craniomaxillofac Trauma Reconstr 7(3): 190-196. Ioannides, C., E. Fossion, W. Boeckx, B. Hermans and D. Jacobs (1994). "Surgical management of the osteoradionecrotic mandible with free vascularised composite flaps." J Craniomaxillofac Surg 22(6): 330-334.
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
Jacobson, A. S., D. Buchbinder, K. Hu and M. L. Urken (2010). "Paradigm shifts in the management of osteoradionecrosis of the mandible." Oral Oncol 46(11): 795801. Jereczek-Fossa, B. A. and R. Orecchia (2002). "Radiotherapy-induced mandibular bone complications." Cancer Treat Rev 28(1): 65-74. Krag, C., S. Holck, G. DeRose, T. Lyczakowski and C. R. Freeman (1982). "Healing of microvascular anastomoses. A comparative study using normal and irradiated recipient vessels for experimental free flaps in rabbits." Scand J Plast Reconstr Surg 16(3): 267-274. Kudo, K. and Y. Fujioka (1978). "Review of bone grafting for reconstruction of discontinuity defects of the mandible." J Oral Surg 36(10): 791-793. Li, B. H., H. J. Jung, S. W. Choi, S. M. Kim, M. J. Kim and J. H. Lee (2012). "Latissimus dorsi (LD) free flap and reconstruction plate used for extensive maxillomandibular reconstruction after tumour ablation." J Craniomaxillofac Surg 40(8): e293-300. Maier, A., A. Gaggl, H. Klemen, G. Santler, U. Anegg, B. Fell, H. Karcher, F. M. SmolleJuttner and G. B. Friehs (2000). "Review of severe osteoradionecrosis treated by surgery alone or surgery with postoperative hyperbaric oxygenation." Br J Oral Maxillofac Surg 38(3): 173-176. Mainous, E. G., G. B. Hart, D. J. Soffa and G. A. Graham (1975). "Hyperbaric oxygen treatment of mandibular osteomyelitis in osteopetrosis." J Oral Surg 33(4): 288291. Margolis, I. B., R. L. Smith and W. C. Davis (1976). "Reconstruction of defects of the mandible." Surgery 79(6): 638-643. Marx, R. E. and J. R. Ames (1982). "The use of hyperbaric oxygen therapy in bony reconstruction of the irradiated and tissue-deficient patient." J Oral Maxillofac Surg 40(7): 412-420. McAllister, B. S. and K. Haghighat (2007). "Bone augmentation techniques." J Periodontol 78(3): 377-396. Miles, B. A., D. P. Goldstein, R. W. Gilbert and P. J. Gullane (2010). "Mandible reconstruction." Curr Opin Otolaryngol Head Neck Surg 18(4): 317-322. Militsakh, O. N., D. I. Wallace, J. D. Kriet, T. T. Tsue and D. A. Girod (2005). "The role of the osteocutaneous radial forearm free flap in the treatment of mandibular osteoradionecrosis." Otolaryngol Head Neck Surg 133(1): 80-83. Mitsimponas, K. T., C. Iliopoulos, P. Stockmann, L. Bumiller, E. Nkenke, F. W. Neukam and K. A. Schlegel (2014). "The free scapular/parascapular flap as a reliable method of reconstruction in the head and neck region: a retrospective analysis of 130 reconstructions performed over a period of 5 years in a single department." J Craniomaxillofac Surg 42(5): 536-543. Moher, D., A. Liberati, J. Tetzlaff, D. G. Altman and P. Group (2009). "Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement." BMJ 339: b2535. Mounsey, R. A., D. H. Brown, T. P. O'Dwyer, P. J. Gullane and G. H. Koch (1993). "Role of hyperbaric oxygen therapy in the management of mandibular osteoradionecrosis." Laryngoscope 103(6): 605-608.
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
Nakatsuka, T., K. Harii, A. Yamada, K. Ueda, S. Ebihara and T. Takato (1996). "Surgical treatment of mandibular osteoradionecrosis: versatility of the scapular osteocutaneous flap." Scand J Plast Reconstr Surg Hand Surg 30(4): 291-298. Rinaldo, A., A. R. Shaha, W. I. Wei, C. E. Silver and A. Ferlito (2002). "Microvascular free flaps: a major advance in head and neck reconstruction." Acta Otolaryngol 122(7): 779-784. Salyer, K. E., H. T. Newsom, R. Holmes and G. Hahn (1977). "Mandibular reconstruction." Am J Surg 134(4): 461-464. Santamaria, E., F. C. Wei and H. C. Chen (1998). "Fibula osteoseptocutaneous flap for reconstruction of osteoradionecrosis of the mandible." Plast Reconstr Surg 101(4): 921-929. Sawhney, R. and Y. Ducic (2013). "Management of pathologic fractures of the mandible secondary to osteoradionecrosis." Otolaryngol Head Neck Surg 148(1): 54-58. Serafin, D., R. Riefkohl, I. Thomas and N. G. Georgiade (1980). "Vascularized ribperiosteal and osteocutaneous reconstruction of the maxilla and mandible: an assessment." Plast Reconstr Surg 66(5): 718-727. Store, G., M. Boysen and P. Skjelbred (2002). "Mandibular osteoradionecrosis: reconstructive surgery." Clin Otolaryngol Allied Sci 27(3): 197-203. Succo, G., M. Berrone, B. Battiston, P. Tos, F. Goia, P. Appendino and E. Crosetti (2014). "Step-by-step surgical technique for mandibular reconstruction with fibular free flap: application of digital technology in virtual surgical planning." Eur Arch Otorhinolaryngol. Suh, J. D., K. E. Blackwell, J. A. Sercarz, M. Cohen, J. H. Liu, C. G. Tang, E. Abemayor and V. Nabili (2010). "Disease relapse after segmental resection and free flap reconstruction for mandibular osteoradionecrosis." Otolaryngol Head Neck Surg 142(4): 586-591. Teng, M. S. and N. D. Futran (2005). "Osteoradionecrosis of the mandible." Curr Opin Otolaryngol Head Neck Surg 13(4): 217-221. Urken, M. L., D. Buchbinder, H. Weinberg, C. Vickery, A. Sheiner, R. Parker, J. Schaefer, P. Som, A. Shapiro, W. Lawson and et al. (1991). "Functional evaluation following microvascular oromandibular reconstruction of the oral cancer patient: a comparative study of reconstructed and nonreconstructed patients." Laryngoscope 101(9): 935-950. Vercruysse, H., Jr., T. Backer and M. Y. Mommaerts (2014). "Outcomes of osseous free flap reconstruction in stage III bisphosphonate-related osteonecrosis of the jaw: systematic review and a new case series." J Craniomaxillofac Surg 42(5): 377386. Wallace, C. G., Y. M. Chang, C. Y. Tsai and F. C. Wei (2010). "Harnessing the potential of the free fibula osteoseptocutaneous flap in mandible reconstruction." Plast Reconstr Surg 125(1): 305-314. Weaver, A. W. and D. B. Smith (1973). "Frozen autogenous mandibular stent-graft for immediate reconstruction in oral cancer surgery." Am J Surg 126(4): 505-506.
ACCEPTED MANUSCRIPT
RI PT
APPENDICES
Study Type
Continent
Total no. primary flaps
Flap Type
Mean Follow-up (months)
Retrospective Case Series
North America
63
Fibula n=38 (5 with pectoralis major, 6 with ALT, 1 with radial)
18.2
Europe
Cannady et al. (2011)
Retrospective Case Series
Celik et al. (2002)
Scapula n=1 Radial n=1
Rectus Abdominis n=7 Anterolateral thigh n=12 (2 with pectoralis major) Iliac crest n=63 (1 with ALT)
6
Fibula n=6
31.0
North America
53
Fibula n=36 Radial n=14 Rectus Abdominis n=1 Anterolateral thigh n=1 Iliac crest n=1
Not reported
Retrospective Case Series
Asia
27
Fibula n=22 Anterolateral thigh n=5
Not reported
Chandarana et al. (2013)
Retrospective Case Series
North America
12
Fibula n=4 Radial n=1 Scapula n=5 Iliac crest n=2
41.0
Chang et al. (2001)
Retrospective Case Series
30
Fibula n=17 Radial n=1 Scapula n=2 Rectus abdominis n=4 Iliac crest n=5
33.0
M AN U
Retrospective Case Series
TE D
Bozec et al. (2006)
SC
Author and Date Bauman et al. (2010)
EP
North America
Retrospective Case Series
South America
5
Fibula n=5
25.0
Retrospective Case Series
Europe
15
Latissimus Dorsi n=15
Not reported
Ioannides et al. (1993)
Retrospective Case Series
Europe
33
Serratus Anterior n=8 Iliac crest n=25
32.0
Militsakh et al. (2005)
Retrospective Case Series
North America
9
Radial n=9
36.0
Nakatsuka et al. (1996)
Retrospective Case Series
Asia
9
Radial n=1 Scapula n=8
Not reported
AC C
Curi et al. (2007) Hillerup et al. (2014)
ACCEPTED MANUSCRIPT
Retrospective Case Series
North America
12
Fibula n=12
45.0
Sawhney et al. (2013)
Retrospective Case Series
North America
37
Fibula n=32 Radial n=3 Scapula n=2
54.0
Store et al. (2002)
Retrospective Case Series
Europe
17
Fibula n=7 Radial n=1 Humerus n=5 Iliac crest n=4
57.0
Suh et al. (2010)
Retrospective Case Series
North America
40
Fibula n=36 Latissimus dorsi n=1 Serratus anterior n=2 Iliac crest n=1
17
M AN U
SC
RI PT
Santamaria et al. (1998)
AC C
EP
TE D
Table 1. Study characteristics
ACCEPTED MANUSCRIPT
63
Bozec et al. (2006) Cannady et al. (2011) Celik et al. (2002)
6
Type of Flap
Reason for Failure
4 (6.3)
Not stated
Vessel thrombosis (n=3) Carotid artery rupture (n=1)
0 (0)
N/A
7 (13.2)
Not stated Fibula n=2 Anterolateral thigh n=1
53 27 3 (11.1)
Chandarana et al. (2013) Chang et al. (2001)
13
4 (3.1) 30
AC C Store et al. (2002) Suh et al. (2010)
Not stated Fibula n=1 Iliac n=2 Scapula n=1 Fibula n=1 Latissimus Dorsi n=1
TE D
5 15
4 (1.4) 1 (20.0) 1 (6.7)
33
5 (15.2)
Iliac n=5
Fistula (n=3)
0 (0)
N/A
1 (11.1)
Scapula n=1
2 (16.7)
Fibula n=2
2 (5.4)
Fibula n=2
Not stated
Venous thrombosis (n=2), infection (n=1), other (n=1) Fistula (n=1) Plate exposure (n=1)
Venous thrombosis (n=4) Technical error (n=1)
9
EP
Curi et al. (2007) Hillerup et al. (2014) Ioannides et al. (1993) Militsakh et al. (2005) Nakatsuka et al. (1996) Santamaria et al. (1998) Sawhney et al. (2013)
RI PT
Bauman et al. (2010)
Total no. of free flap failures (%)
SC
Total free flaps (n)
M AN U
Study
9
12 37
17 40
Vessel thrombosis (n=1) Fistula (n=1) Skin paddle necrosis (n=2)
Infection (n=2) 2 (11.8)
Fibula n=2
0 (0)
N/A
Table 2. Free Flap Failures
ACCEPTED MANUSCRIPT
Baumann et al. (2010) (Baumann, Yu et al. 2011)
Total Flap Complications (n) 20
Bozec et al. (2006) (Bozec, Poissonnet et al. 2006) Cannady et al. (2011)
2
Celik et al. (2002) Chandarana et al. (2013)
3 20
Reason Infection (n=8) Fistula (n=6) Haematoma (n=2) Vessel Thrombosis (n=3) Vessel Rupture (n=1)
RI PT
Study
6
2
EP
Curi et al. (2007)
TE D
Chang et al. (2001)
M AN U
SC
13
Infection (n=1) Fistula (n=1) Skin paddle necrosis (n=1) Fistula (n=2) Vessel thrombosis (n=4) Vessel rupture (n=1) Other (n=5) Fistula (n=3) Infection (n=1) Skin paddle necrosis (n=1) Fistula (n=6) Non-union (n=4) Plate exposure (n=5) Haematoma (n=1) Other (n=3) Infection (n=1) Skin paddle necrosis (n=2) Vessel thrombosis (n=2) Fistula (n=1) Vessel thrombosis (n=1) N/A Infection (n=3) Fistula (n=2) Haematoma (n=2) Vessel Thrombosis (n=4) N/A Skin paddle necrosis (n=1) Fistula (n=1) Non-union (n=1) Skin paddle necrosis (n=1) Fistula (n=2) Vessel thrombosis (n=1) Skin paddle necrosis (n=1) Non-union (n=4)
AC C
Hillerup et al. (2014) Ioannides et al. (1993)
0 13
Militsakh et al. (2005) Nakatsuka et al. (1996)
0 3
Santamaria et al. (1998)
4
Sawhney et al. (2013)
15
ACCEPTED MANUSCRIPT
Plate exposure (n=3) 7 Infection (n=3) Plate exposure n=1 38 Infection n=7 Fistula n=6 Plate exposure n=17 Table 3. Free Flap Complications
Store et al. (2002)
AC C
EP
TE D
M AN U
SC
RI PT
Suh et al. (2010)
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT
Highlights
•
AC C
EP
TE D
M AN U
SC
• •
We conduct a worldwide systematic literature review of reported outcomes of microvascular free flap reconstruction in mandibular osteoradionecrosis. We examine the rates of free flap success and complications, and the different types of free flap tissue used. There is a significant failure and complication rate. There is a need for higher powered institutional studies to assess different types of free flap tissue and their use in mandibular reconstruction.
RI PT
•
S1010-5182(15)00058-X
DOI:
10.1016/j.jcms.2015.03.006
Reference:
YJCMS 1989
To appear in:
Journal of Cranio-Maxillo-Facial Surgery
Received Date: 12 December 2014 Revised Date:
2 March 2015
Accepted Date: 3 March 2015
Please cite this article as: Lee M, Chin RY, Eslick G, Sritharan N, Paramaesvaran S, Outcomes of Microvascular Free Flap Reconstruction for Mandibular Osteoradionecrosis: A Systematic Review, Journal of Cranio-Maxillofacial Surgery (2015), doi: 10.1016/j.jcms.2015.03.006. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Title: Outcomes of Microvascular Free Flap Reconstruction for Mandibular Osteoradionecrosis: A Systematic Review.
Keywords: Osteoradionecrosis, Mandible, Free Tissue Flaps, Surgical Flaps, Head
Authors: Migie Lee1 Ronald Y Chin2 Guy Eslick3 Niranjan Sritharan1
Affiliations:
M AN U
Suchitra Paramaesvaran2
SC
RI PT
and Neck Neoplasms
1
Department of Otolaryngology, Head and Neck Surgery, Nepean Hospital, Sydney
2
University of Sydney, Australia
3
The Whiteley-Martin Research Centre, The University of Sydney, Nepean Hospital,
TE D
Sydney
Corresponding author: Ronald Y Chin
AC C
EP
Address: Department of Otolaryngology, Head and Neck Surgery, Nepean Hospital Derby Street, Penrith NSW 2750 Email: [email protected]
ACCEPTED MANUSCRIPT
ABSTRACT Introduction Osteoradionecrosis of the mandible is a devastating complication of radiotherapy in patients with head and neck cancer. Many cases present at a late stage, from months
RI PT
to years following completion of radiation therapy. When medical treatment fails, surgery may be required with a variety of free flaps available for microvascular reconstructive techniques.
Objective
SC
To conduct a systematic review of the literature investigating the outcomes of free flap reconstruction of the jaw in mandibular osteoradionecrosis and determine the
M AN U
failure rates of different flap tissue.
Methods
A systematic literature search was performed using Medline (Ovid) Pubmed and Embase databases and Google Scholar. Primary outcome measures were flap failures and complications, with donor site complications representing the secondary outcome
Results
TE D
measure. Analysis of pooled outcomes was undertaken for different flaps.
333 articles were identified and 15 articles met the final inclusion criteria, detailing 368 primary free tissue flap transfers. There was a flap failure rate of 9.8%. There
EP
were 146 post-operative complications (39.7%), the most common being fistula
AC C
formation (8.4%), hardware plate exposure (7.1%) and flap wound infections (6.5%).
Conclusion
The fibula is the workhorse free flap for reconstruction in mandibular osteoradionecrosis. Evidence to date is largely limited with the need for larger powered multi-institutional prospective studies to determine the ideal flap donor tissue and evaluate patient and treatment predictors of free flap outcomes in order to tailor the best patient-based surgical approach for mandibular osteoradionecrosis.
ACCEPTED MANUSCRIPT
INTRODUCTION Osteoradionecrosis (ORN) is one of the most debilitating complications of radiation therapy in patients undergoing treatment for head and neck cancer. It is defined as exposed irradiated bone that fails to heal over a three-month period in the absence of
RI PT
residual or recurrent tumour (Epstein, Wong et al. 1987) and can affect any bony component of the craniomaxillofacial skeleton (Teng and Futran 2005).
The management of ORN comprises primarily on symptomatic management
and prevention of further disease progression. Despite appropriate management, many patients will progress to advanced ORN disease to a stage where tissue may become
SC
necrotic and overhwlemed by infection, making it difficult to salvage affected bone (Alam, Nuara et al. 2009).
With advancements in reconstructive techniques, there is increasing evidence
M AN U
for improved outcomes with microvascular free flap (MVFF) transfer following segmental resection of non-viable bone in osteoradionecrosis. MVFF in reconstructing ORN defects has an advantage over multi-stage reconstructions as it allows simultaneous reconstruction of both hard and soft tissue components of the defect with tissue from a separate site (Buchbinder and St Hilaire 2006).
Historically, it has been shown that higher complication rates are experienced when reconstructing tissue previously exposed to radiation treatment (Weaver and
TE D
Smith 1973, Margolis, Smith et al. 1976, Salyer, Newsom et al. 1977, Kudo and Fujioka 1978, Adamo and Szal 1979, Serafin, Riefkohl et al. 1980) with the key challenge in the inherent poor wound healing in irradiated tissue. Radiation exposure compromises the integrity of recipient vessels and negatively affects free flap viability (Krag, Holck et
EP
al. 1982), with both pre-operative and post-operative radiotherapy associated with an increased flap complication rate (Deutsch, Kroll et al. 1999). With advancements in technology and surgical techniques, the rates of flap success
AC C
have increased to a reported rate of 86-100% (Celik, Wei et al. 2002, Store, Boysen et al. 2002, Ang, Black et al. 2003, Militsakh, Wallace et al. 2005, Buchbinder and St Hilaire 2006). Whilst free flap outcome is arguably primarily due to surgical technique, a better understanding of clinical predictors and contributing factors is necessary to help optimise peri-operative and post-operative management. The aim of this systematic review is to present collective evidence from up to date literature and further define factors contributing the flap failure by exploring the outcomes of microvascular free tissue transfer reconstructions in patients with mandibular osteoradionecrosis.
ACCEPTED MANUSCRIPT
METHODS
Study Protocol We followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses
RI PT
(PRISMA) guidelines (Moher, Liberati et al. 2009). Relevant articles were identified
through a systematic search of the databases MEDLINE, PubMed, Embase, Cochrane
databases and Google Scholar through to September 1, 2014. The search used the terms ‘Free Tissue Flaps’ AND ‘Osteoradionecrosis’ OR ‘Osteoradionecrosis’ AND ‘Mandibular Reconstruction’, which were searched as text word and as exploded
SC
medical subject headings where possible. The reference lists of relevant articles were
also hand-searched for appropriate studies. Conference proceedings were not examined. No language restrictions were used in either the search or study selection.
M AN U
A search for unpublished literature was not performed.
Study Selection
We included all types of studies that met the following inclusion criteria: (1) Osteoradionecrosis was clearly described by clinical examination and/or confirmed radiologically; (2) the total sample size of the study exceeded 5 free flaps; (3) results examined the outcomes of microvascular free tissue transfer reconstruction; (4) the
TE D
point estimate was reported as an odds ratio (OR), or the data was presented such that an OR could be calculated; (5) the 95% confidence interval (CI) was reported, or the data was presented such that the CI could be calculated. Two independent reviewers initially screened the titles and abstracts of the search for possible inclusion and the full
EP
text of all screened studies were obtained for assessment. Any uncertainty or disagreement was resolved by discussion with a third independent reviewer. We
AC C
excluded studies that did not meet the inclusion criteria.
Data Extraction
One reviewer (M.L.) performed the data extraction using a standardized data extraction form. Information was extracted on the publication year, study design, number of cases, population type, country, continent, mean age, gender, adjuvant treatment, months of follow-up, flap failure rates and incidence of free flap complications. Quality of the studies was not assessed as all studies found were observational case series. In articles that provided a contact email address, authors were contacted for missing data.
ACCEPTED MANUSCRIPT
Figure 1. Study selection flowchart
RI PT
From the initial literature search, 333 titles were retrieved and after removal of
duplicates, screening and exclusion based on criteria, a final 15 articles met the final
inclusion criteria (Ioannides, Fossion et al. 1994, Nakatsuka, Harii et al. 1996, Curi and Dib 1997, Santamaria, Wei et al. 1998, Chang, Oh et al. 2001, Celik, Wei et al. 2002, Store, Boysen et al. 2002, Militsakh, Wallace et al. 2005, Bozec, Poissonnet et al.
SC
2006, Suh, Blackwell et al. 2010, Baumann, Yu et al. 2011, Cannady, Dean et al. 2011, Chandarana, Chanowski et al. 2013, Sawhney and Ducic 2013, Hillerup, Elberg et al.
M AN U
2014).
Statistical Analysis
Pooled odds ratio estimates and 95% confidence intervals were calculated for risk factors of mandibular osteoradionecrosis using a random effects model (DerSimonian and Laird 1986). We tested heterogeneity with Cochran’s Q statistic, with P<0.10
TE D
indicating heterogeneity, and quantified the degree of heterogeneity using the I2 statistic, which represents the percentage of the total variability across studies which is due to heterogeneity that is not due to chance (Higgins, Thompson et al. 2003). All
AC C
EP
analyses were performed with Comprehensive Meta-analysis (version 2.0).
ACCEPTED MANUSCRIPT
RESULTS Study Characteristics
RI PT
Table 1 shows selected characteristics of the identified studies (Ioannides, Fossion et al. 1994, Nakatsuka, Harii et al. 1996, Curi and Dib 1997, Santamaria, Wei et al. 1998, Chang, Oh et al. 2001, Celik, Wei et al. 2002, Store, Boysen et al. 2002, Militsakh, Wallace et al. 2005, Bozec, Poissonnet et al. 2006, Suh, Blackwell et al. 2010,
Baumann, Yu et al. 2011, Cannady, Dean et al. 2011, Chandarana, Chanowski et al.
SC
2013, Sawhney and Ducic 2013, Hillerup, Elberg et al. 2014). Eight studies examined populations from North America, one from South America, four from Europe and two
from Asia. Of the 11 studies that reported follow-up periods, the average duration was
M AN U
35.4 months. Mean age was 57.4 years, and the reported percentage of males was 68% (58%-72%), I2=37.52, p=0.07 and smokers 55% (18%-88%), I2=92.07, p<0.001. Squamous cell carcinoma comprised the majority of cases, 83% (77%-89%), I2=0.00, p=0.61 and the mean radiotherapy dose 67.71 gray (Gy). Adjuvant Treatment
Of those that reported adjuvant treatment, one quarter received adjuvant
TE D
chemotherapy (25%(17%-36%), I2=37.63, p=0.16) and more than half underwent hyperbaric oxygen therapy (HBO) (53%(40%-65%), I2=70.83, p<0.01.
EP
Table 1. Study characteristics
AC C
Table 2. Free Flap Failures
ACCEPTED MANUSCRIPT
Free Flap Donor Sites A total of 368 primary free flaps were performed in 15 different studies. Used donor sites comprised of that from the fibula (n= 215), iliac crest (n=43), radial (n=31),
(n=12), serratus anterior (n=10) and the humerus (n=5).
Flap Failures
RI PT
scapula (n=18), anterolateral thigh (n=18), latissimus dorsi (n=16), rectus abdominis
There were 36 flap failures (9.8% (9%-16%), I2=0.00, p=0.56) requiring revision
SC
operations. These flaps originated from donor sites fibula (n=10), iliac crest (n=7),
scapula (n=2) and anterolateral thigh (n=1) and latissimus dorsi (n=1). In the 15 failures unaccounted for (from 4 studies), donor sites were not stated. Of those that failed, 5
M AN U
had fistula formation, 3 became otherwise infected, 10 had vessel thromboses and 2 had skin paddle necrosis. One case had carotid artery rupture in which the flap that was connected to the vessels in the contralateral neck was lost during resuscitation. This patient subsequently died from multiorgan failure.
AC C
EP
TE D
Figure 2. Forest plot for flap failure event rate per study
ACCEPTED MANUSCRIPT
The pooled event rate for patients who underwent free flap reconstruction for mandibular osteoradionecrosis is 0.12 (95%CI 0.09-0.16). Failure rates according to tissue type were: iliac crest (n=7, 16.3%), scapula (n=2,
RI PT
11.1%) and anterolateral thigh (n=1, 5.6%) and fibula (n=10, 4.7%),
Other Flap Complications
There were 146 post-operative complications (39.7%) that otherwise did not result in
SC
flap failure. The most common complications fistula formation (n=31), hardware plate
exposure (n=26) and flap wound infections (n=24). Vessel complications were noted in a total 5 patients; thromboses were seen in 16 free flaps (4.3%), haematoma formation
M AN U
in 5 (1.4%) and 2 patients (0.5%) had carotid artery rupture following flap reconstruction.
Table 3. Free Flap Complications
DISCUSSION
TE D
A total of 20 (5.4%) donor site complications were reported.
Osteonecrosis is a serious complication not limited to the effects of radiotherapy but
EP
also medication-induced side effects e.g. bisphosphonates (Vercruysse, Backer et al.
2014). When it does arise, it can cause significant morbidity particularly that is devastating to the patient. The focus of this review is mandibular osteoradionecrosis in
AC C
head and neck cancer patients, which has variable incidence rates reported in the literature, ranging from as low as 0.4% to as high as 56% (Jereczek-Fossa and Orecchia 2002). In advanced disease, paradigm shifts in the management of mandibular osteoradionecrosis have seen surgical resection and immediate free tissue transfer performed for stage 3 disease (Jacobson, Buchbinder et al. 2010). Free flap reconstruction in the irradiated jaw is difficult. Choosing the right donor site and harvesting an appropriate flap requires great precision and skill. Identification and dissection of recipient vessels can be arduous and necessitates selection of vessels
ACCEPTED MANUSCRIPT
arising from outside the irradiated field, often from the contralateral neck (Cordeiro, Disa et al. 1999, Ang, Black et al. 2003). Surgical reconstruction of the mandible in patients with osteoradionecrosis is reserved for advanced disease. In the treatment of early disease, the authors
RI PT
recommend oral hygiene, optimization of nutritional status and multidisciplinary
management including dental, head and neck surgery and plastics surgery review. In cases that are more severe, debridement of necrotic tissue and appropriate use of antibiotics with involvement of infectious diseases are necessary.
In treatment early stage disease, management is conservative comprising of
SC
debridement of necrotic tissue, antibiotics and in some institutions, hyperbaric oxygen therapy (HBO). From the 1960s, HBO had been utilised as an additional treatment modality in the management of osteoradionecrosis, popularized by Marx (Marx and
M AN U
Ames 1982) as an adjunct to soft tissue flaps in managing irradiated tissue. It continues to be utilized by some institutions and although in the days of its inception, HBO did show promising results in the treatment of ORN (Mainous, Hart et al. 1975, Hart and Mainous 1976, Davis, Dunn et al. 1979), current literature demonstrates no benefit. Recent evidence has questioned any significant benefit (Mounsey, Brown et al. 1993, Maier, Gaggl et al. 2000) with a multicenter randomized, double-blinded, placebo-controlled trial in 2004 showing no benefit of HBO treatment in patients for
TE D
osteoradionecrosis of the jaw (Annane, Depondt et al. 2004). Reconstructive procedures should be reserved for difficult and severe cases where conservative management has been unsuccessful in achieving adequate healing. Surgical repair of osteoradionecrotic tissue is a challenge both peri-operatively
EP
and post-operatively. Previous surgery obliterates tissue planes and radiation-induced tissue breakdown leads to problems with wound healing(Ang, Black et al. 2003). Local wound healing problems may manifest as infection, dehiscence, fistula formation
AC C
and/or plate exposure and rates of such complications range from 8 to 43% (Celik, Wei et al. 2002, Coskunfirat, Wei et al. 2005), the upper limit close to that of this review (42.7%). Progression of local wound complications, or other microvascular events e.g. thrombosis, can lead to partial or total free flap loss requiring further surgery for a second free flap or regional myocutaneous flap (Ang, Black et al. 2003). The overall flap failure rate was 9.8% (n=36). Flap tissue type was identified in
21 flaps across 11 studies. 4 of the 15 studies did not identify the types of flaps that failed, leaving 15 flap failures unaccounted for.
ACCEPTED MANUSCRIPT
In mandibular reconstruction, restoration of bone continuity is not the only key to success. The surgery needs to achieve adequate bone height and width and supporting of overlying soft tissue structures to restore jaw motion (McAllister and Haghighat 2007). The masseter muscle is the strongest muscle in the body and does
RI PT
not stretch uniformly for major jaw movement thus a good supportive bone and soft
tissue structural graft is crucial to maintain the functional integrity of the jaw. The soft tissue needs to be forgiving in both size as quality thus when considering the use of non-vascularised bone grafts, the ideal tissue should have enough bulk, vascularity and cellularity to achieve good graft application (Arotiba, Effiom et al. 2012).
SC
Four osteocutaneous flaps are commonly used for mandible reconstruction:
fibula flap, iliac crest flap, scapula flap and the radial flap. Li et al (Li, Jung et al. 2012)
M AN U
conducted a cohort study in which 116 patients underwent latissimus dorsi free flap and plate reconstruction following advanced oro-mandibular tumour resection. The series demonstrated a very good survival rate (99.1%). Despite favourable results, the use of latissimus dorsi along with serratus anterior and upper arm (humerus) flaps is becomingling increasingly less common, largely due to the limited available bone to repair mandible defects, and the short pedicle available, which make the flaps difficult to anastomose.
TE D
The iliac crest flap is usually considered when there is a contraindication to the fibula flap. Patients with signs of lower limb vascular insufficiency or a history of lower limb fracture are deemed unsuitable for the fibula flap. It does offer certain unique advantages over the fibula flap in the quality and quantity of bone available, whereby
EP
the resting shape of the iliac crest bone resembles the mandible anatomically, requiring minimal osteotomy. The major drawback is that whilst it has robust blood supply to the bone and internal oblique muscle, issues can arise in the blood supply to the skin,
AC C
whereby the supplying perforators of the deep circumflex iliac artery can tear easily as they pass through the layers of the abdominal wall (Chepeha 2001). The iliac crest flap had a success rate of 76.6%, with the most common failure reason attributed to venous thrombosis (Ioannides, Fossion et al. 1994). The scapula flap is a reasonable option with its main feature being that of its
abundant soft tissue and its two discrete skin paddles, which allows for greater flexibility in repairing complex facial defects. A recent retrospective institutional study found the free scapula/parascapular flap to be a versatile and reliable flap for head and neck reconstructions with a good success rate (96%) and a low complication rate (2.3%) (Mitsimponas, Iliopoulos et al. 2014). One limitation of this flap is its limited
ACCEPTED MANUSCRIPT
length, and the thin and fine nature of the bone. Another disadvantage is the need for patient repositioning during the surgery in order to harvest the flap, precluding simultaneous harvesting at the time of tumour resection and prolonging the operating time (Miles, Goldstein et al. 2010).
RI PT
The radial forearm free flap is a reasonable alternative in its key property of superior blood supply compared to other tissue options. It offers a large, thin and pliable skin segment that is widely favored for soft tissue reconstruction of
pharyngoesophageal defects as a fasciocutaneous flap. Additional bulk can be
included with use of the brachioradialis muscle and it has good nerve supply for
SC
optimal recovery of sensory function (Disa and Cordeiro 2000). As an osteocutaneous flap however, the radius in limited in the lack of bone available for osteotomy (AbdelKader, Tamam et al.). There is approximately 10cm of bone available to be taken and
M AN U
although it is cortical bone, only one third of the cross-sectional area can be taken without increasing the risk of mechanical stress fracture (Clark, Greenwood et al. 2004). This compromises the thickness of the bone and thus only a small bony defect can be repaired using the radial flap, unless combined with other donor sites (Rinaldo, Shaha et al. 2002). Of the total 31 radial free flaps, no flap failures were reported. However, it is unclear whether those undertaken in the studies included osteotomy or if they were fasciocutaneous flaps only.
TE D
The fibula microvascular free flap for head and neck reconstruction was first introduced by Hidalgo in 1989(Hidalgo 1989) and is now considered as the workhorse for mandible reconstruction (George and Krishnamurthy 2013, Succo, Berrone et al. 2014) (Ang, Black et al. 2003). The fibula osteocutaneous free flap has quickly gained
EP
popularity over other vascularized bone flaps in recent years for several reasons. The fibula benefits from its quality of bone, with good cortical thickness, and the generous length of bone available (up to 25-30cm), which permits multiple osteotomies even
AC C
whilst the pedicle is still attached (Urken, Buchbinder et al. 1991) (Hao, Chen et al. 1999). The vasculature is also ideal. The flap’s dominant arterial supply is from the peroneal artery and venous drainage via the 2 venae comitantes, which have an average caliber of 1.5mm and 3mm respectively. These vessel diameters closely match that of most recipient vessels in the neck facilitating effective anastomoses. Its long and reliable vascular pedicle (up to 12-15cm) is useful when confronted with recipient vessels that are difficult to locate in heavily irradiated tissue (Wallace, Chang et al. 2010). Furthermore, the fibula provides the bony platform for eventual prosthetic rehabilitation, allowing the placement of intraosseous dental implants. The fibula free
ACCEPTED MANUSCRIPT
flap offers considerable advantages over its counterparts as the ideal flap of choice for mandibular reconstruction and it was by far the most common free flap tissue used (n=215) and, from the free flap failure data reported, had a good success rate (95.3%). With the great variations across the studies, and the small numbers of some
flap site were unable to be conducted.
RI PT
e.g. humerus (n=5) sufficiently powered subset analyses to determine the best donor
The purpose of this systematic review was to summarize the reported literature to date in the variety of free flap reconstructions used and the outcomes of different
practice across different institutions. We appreciate that this review is a retrospective
SC
pooling of case series predisposed to the drawbacks associated with such studies. We also acknowledge the assumed limitations in the outdated nature of some articles, particularly those predating the new millennium (Ioannides, Fossion et al. 1994, Curi
M AN U
and Dib 1997, Santamaria, Wei et al. 1998), with which current practice may now vastly differ to that carried out in the older studies. In the 15 studies included in this review, all retrospective case series, there were a total 368 primary microvascular free flaps studied with a 9.8% failure rate. Flap failure requires a revision operation and in most instances, necessitates a secondary free flap from another donor site. This leads to further morbidity and a longer hospital stay, which calls for measures in acquiring a better understanding of the factors associated with flap loss. Direct associations
TE D
between clinical and patient factors with flap loss overall were not explored in the included articles in this systematic review, thus pooled outcomes of such could not be reported. In the literature, important factors that have been associated with graft survival include the length of mandibular defect, timing of the reconstruction
EP
(immediate or delayed), cancer diagnosis, intraoral communication, estimated blood loss and the duration of post-operative antibiotics (August, Tompach et al. 2000). Furthermore, longer close follow-up periods are needed. All of the 11 studies that
AC C
reported follow-up period durations reported outcomes within a 5 year post-operative period. Long-term outcomes and potential adverse consequences are not known. This is the first systematic review looking at the surgical outcomes of
reconstruction with microvascular free flaps used in patients with mandibular osteoradionecrosis. The results show the challenges inherent in successful microvascular free flap reconstruction in patients with mandibular osteoradionecrosis, however the systematic review is limited in the retrospective nature of all studies and the inherent selection bias in the patient populations. The lack of randomized trials, variability in the donor flap site used and the potential for confounding factors e.g.
ACCEPTED MANUSCRIPT
adjuvant medical treatment and surgical technique, limit an objective analysis. As institutional practices in relation to flap choice and surgical technique and consistencies in follow-up reporting of outcomes are likely to vary, future prospective studies with indepth analyses of the predictors of flap survival are needed. Recommendations for
RI PT
future research directions include the investigation of predictive patient and clinical factors and determination of the ideal donor flap site associated with the best outcomes.
CONCLUSIONS
SC
Osteoradionecrosis of the mandible is an uncommon but significant complication of
radiotherapy, where surgical treatment for advanced disease can carry great morbidity with post-operative complications. Whilst a number of free flap tissue types can be
M AN U
used, the fibula free flap continues to be the gold standard and workhorse flap in the reconstruction of mandibular defects with a good success rate. Higher-powered prospective studies that closely examine patient and clinical factors associated with flap outcomes will lead to greater understanding of predictors of flap survival and help guide individualized patient approaches to appropriate microvascular reconstruction in mandibular osteoradionecrosis.
AC C
EP
TE D
Conflicts of Interest: None.
ACCEPTED MANUSCRIPT
REFERENCES
AC C
EP
TE D
M AN U
SC
RI PT
Abdel-Kader, M. S., A. A. Tamam, A. A. Elderwy, M. Gad, M. A. El-Gamal, A. Kurkar and A. S. Safwat (2013). "Management of symptomatic ureteral calculi during pregnancy: Experience of 23 cases." Urol Ann 5(4): 241-244. Adamo, A. K. and R. L. Szal (1979). "Timing, results, and complications of mandibular reconstructive surgery: report of 32 cases." J Oral Surg 37(10): 755763. Alam, D. S., M. Nuara and J. Christian (2009). "Analysis of outcomes of vascularized flap reconstruction in patients with advanced mandibular osteoradionecrosis." Otolaryngol Head Neck Surg 141(2): 196-201. Ang, E., C. Black, J. Irish, D. H. Brown, P. Gullane, B. O'Sullivan and P. C. Neligan (2003). "Reconstructive options in the treatment of osteoradionecrosis of the craniomaxillofacial skeleton." Br J Plast Surg 56(2): 92-99. Annane, D., J. Depondt, P. Aubert, M. Villart, P. Gehanno, P. Gajdos and S. Chevret (2004). "Hyperbaric oxygen therapy for radionecrosis of the jaw: a randomized, placebo-controlled, double-blind trial from the ORN96 study group." J Clin Oncol 22(24): 4893-4900. Arotiba, G. T., A. O. Effiom, A. S. Ayodele, M. O. Ogundana, M. O. Gbotolorun, H. O. Olasoji, O. James, A. L. Ladeinde, V. I. Ugboko, K. C. Ndukwe, I. C. Ikem and R. O. Braimah (2012). "A classification system for recurrent ameloblastoma of the jaws-review of 30 cases in Nigerians." Nig Q J Hosp Med 22(1): 44-51. August, M., P. Tompach, Y. Chang and L. Kaban (2000). "Factors influencing the long-term outcome of mandibular reconstruction." J Oral Maxillofac Surg 58(7): 731-737; discussion 738. Baumann, D. P., P. Yu, M. M. Hanasono and R. J. Skoracki (2011). "Free flap reconstruction of osteoradionecrosis of the mandible: a 10-year review and defect classification." Head Neck 33(6): 800-807. Bozec, A., G. Poissonnet, S. Converset, J. Vallicioni, F. Demard and O. Dassonville (2006). "[Fibula free flap for reconstruction of extensive mandibular osteoradionecrosis]." Ann Otolaryngol Chir Cervicofac 123(2): 98-106. Buchbinder, D. and H. St Hilaire (2006). "The use of free tissue transfer in advanced osteoradionecrosis of the mandible." J Oral Maxillofac Surg 64(6): 961964. Cannady, S. B., N. Dean, A. Kroeker, T. A. Albert, E. L. Rosenthal and M. K. Wax (2011). "Free flap reconstruction for osteoradionecrosis of the jaws--outcomes and predictive factors for success." Head Neck 33(3): 424-428. Celik, N., F. C. Wei, H. C. Chen, M. H. Cheng, W. C. Huang, F. C. Tsai and Y. C. Chen (2002). "Osteoradionecrosis of the mandible after oromandibular cancer surgery." Plast Reconstr Surg 109(6): 1875-1881. Chandarana, S. P., E. J. Chanowski, K. A. Casper, G. T. Wolf, C. R. Bradford, F. P. Worden, A. Eisbruch and D. B. Chepeha (2013). "Osteocutaneous free tissue transplantation for mandibular osteoradionecrosis." J Reconstr Microsurg 29(1): 5-14. Chang, D. W., H. K. Oh, G. L. Robb and M. J. Miller (2001). "Management of advanced mandibular osteoradionecrosis with free flap reconstruction." Head Neck 23(10): 830-835.
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
Chepeha, D. B., Teknos, T.N., Ed. (2001). Microvascular Free Flaps in Head and Neck Reconstruction, Lippincott Williams & Wilkins. Clark, S., M. Greenwood, R. J. Banks and R. Parker (2004). "Fracture of the radial donor site after composite free flap harvest: a ten-year review." Surgeon 2(5): 281286. Cordeiro, P. G., J. J. Disa, D. A. Hidalgo and Q. Y. Hu (1999). "Reconstruction of the mandible with osseous free flaps: a 10-year experience with 150 consecutive patients." Plast Reconstr Surg 104(5): 1314-1320. Coskunfirat, O. K., F. C. Wei, W. C. Huang, M. H. Cheng, W. G. Yang and Y. M. Chang (2005). "Microvascular free tissue transfer for treatment of osteoradionecrosis of the maxilla." Plast Reconstr Surg 115(1): 54-60. Curi, M. M. and L. L. Dib (1997). "Osteoradionecrosis of the jaws: a retrospective study of the background factors and treatment in 104 cases." J Oral Maxillofac Surg 55(6): 540-544; discussion 545-546. Davis, J. C., J. M. Dunn, G. A. Gates and R. D. Heimbach (1979). "Hyperbaric oxygen. A new adjunct in the management of radiation necrosis." Arch Otolaryngol 105(2): 58-61. DerSimonian, R. and N. Laird (1986). "Meta-analysis in clinical trials." Control Clin Trials 7(3): 177-188. Deutsch, M., S. S. Kroll, N. Ainsle and B. Wang (1999). "Influence of radiation on late complications in patients with free fibular flaps for mandibular reconstruction." Ann Plast Surg 42(6): 662-664. Disa, J. J. and P. G. Cordeiro (2000). "Mandible reconstruction with microvascular surgery." Semin Surg Oncol 19(3): 226-234. Epstein, J. B., F. L. Wong and P. Stevenson-Moore (1987). "Osteoradionecrosis: clinical experience and a proposal for classification." J Oral Maxillofac Surg 45(2): 104-110. George, R. K. and A. Krishnamurthy (2013). "Microsurgical free flaps: Controversies in maxillofacial reconstruction." Ann Maxillofac Surg 3(1): 72-79. Hao, S. P., H. C. Chen, F. C. Wei, C. Y. Chen, A. R. Yeh and J. L. Su (1999). "Systematic management of osteoradionecrosis in the head and neck." Laryngoscope 109(8): 1324-1327; discussion 1327-1328. Hart, G. B. and E. G. Mainous (1976). "The treatment of radiation necrosis with hyperbaric oxygen (OHP)." Cancer 37(6): 2580-2585. Hidalgo, D. A. (1989). "Fibula free flap: a new method of mandible reconstruction." Plast Reconstr Surg 84(1): 71-79. Higgins, J. P., S. G. Thompson, J. J. Deeks and D. G. Altman (2003). "Measuring inconsistency in meta-analyses." BMJ 327(7414): 557-560. Hillerup, S., J. J. Elberg, J. J. Thorn and M. Andersen (2014). "Reconstruction of irradiated mandible after segmental resection of osteoradionecrosis-a technique employing a microvascular latissimus dorsi flap and subsequent particulate iliac bone grafting." Craniomaxillofac Trauma Reconstr 7(3): 190-196. Ioannides, C., E. Fossion, W. Boeckx, B. Hermans and D. Jacobs (1994). "Surgical management of the osteoradionecrotic mandible with free vascularised composite flaps." J Craniomaxillofac Surg 22(6): 330-334.
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
Jacobson, A. S., D. Buchbinder, K. Hu and M. L. Urken (2010). "Paradigm shifts in the management of osteoradionecrosis of the mandible." Oral Oncol 46(11): 795801. Jereczek-Fossa, B. A. and R. Orecchia (2002). "Radiotherapy-induced mandibular bone complications." Cancer Treat Rev 28(1): 65-74. Krag, C., S. Holck, G. DeRose, T. Lyczakowski and C. R. Freeman (1982). "Healing of microvascular anastomoses. A comparative study using normal and irradiated recipient vessels for experimental free flaps in rabbits." Scand J Plast Reconstr Surg 16(3): 267-274. Kudo, K. and Y. Fujioka (1978). "Review of bone grafting for reconstruction of discontinuity defects of the mandible." J Oral Surg 36(10): 791-793. Li, B. H., H. J. Jung, S. W. Choi, S. M. Kim, M. J. Kim and J. H. Lee (2012). "Latissimus dorsi (LD) free flap and reconstruction plate used for extensive maxillomandibular reconstruction after tumour ablation." J Craniomaxillofac Surg 40(8): e293-300. Maier, A., A. Gaggl, H. Klemen, G. Santler, U. Anegg, B. Fell, H. Karcher, F. M. SmolleJuttner and G. B. Friehs (2000). "Review of severe osteoradionecrosis treated by surgery alone or surgery with postoperative hyperbaric oxygenation." Br J Oral Maxillofac Surg 38(3): 173-176. Mainous, E. G., G. B. Hart, D. J. Soffa and G. A. Graham (1975). "Hyperbaric oxygen treatment of mandibular osteomyelitis in osteopetrosis." J Oral Surg 33(4): 288291. Margolis, I. B., R. L. Smith and W. C. Davis (1976). "Reconstruction of defects of the mandible." Surgery 79(6): 638-643. Marx, R. E. and J. R. Ames (1982). "The use of hyperbaric oxygen therapy in bony reconstruction of the irradiated and tissue-deficient patient." J Oral Maxillofac Surg 40(7): 412-420. McAllister, B. S. and K. Haghighat (2007). "Bone augmentation techniques." J Periodontol 78(3): 377-396. Miles, B. A., D. P. Goldstein, R. W. Gilbert and P. J. Gullane (2010). "Mandible reconstruction." Curr Opin Otolaryngol Head Neck Surg 18(4): 317-322. Militsakh, O. N., D. I. Wallace, J. D. Kriet, T. T. Tsue and D. A. Girod (2005). "The role of the osteocutaneous radial forearm free flap in the treatment of mandibular osteoradionecrosis." Otolaryngol Head Neck Surg 133(1): 80-83. Mitsimponas, K. T., C. Iliopoulos, P. Stockmann, L. Bumiller, E. Nkenke, F. W. Neukam and K. A. Schlegel (2014). "The free scapular/parascapular flap as a reliable method of reconstruction in the head and neck region: a retrospective analysis of 130 reconstructions performed over a period of 5 years in a single department." J Craniomaxillofac Surg 42(5): 536-543. Moher, D., A. Liberati, J. Tetzlaff, D. G. Altman and P. Group (2009). "Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement." BMJ 339: b2535. Mounsey, R. A., D. H. Brown, T. P. O'Dwyer, P. J. Gullane and G. H. Koch (1993). "Role of hyperbaric oxygen therapy in the management of mandibular osteoradionecrosis." Laryngoscope 103(6): 605-608.
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
Nakatsuka, T., K. Harii, A. Yamada, K. Ueda, S. Ebihara and T. Takato (1996). "Surgical treatment of mandibular osteoradionecrosis: versatility of the scapular osteocutaneous flap." Scand J Plast Reconstr Surg Hand Surg 30(4): 291-298. Rinaldo, A., A. R. Shaha, W. I. Wei, C. E. Silver and A. Ferlito (2002). "Microvascular free flaps: a major advance in head and neck reconstruction." Acta Otolaryngol 122(7): 779-784. Salyer, K. E., H. T. Newsom, R. Holmes and G. Hahn (1977). "Mandibular reconstruction." Am J Surg 134(4): 461-464. Santamaria, E., F. C. Wei and H. C. Chen (1998). "Fibula osteoseptocutaneous flap for reconstruction of osteoradionecrosis of the mandible." Plast Reconstr Surg 101(4): 921-929. Sawhney, R. and Y. Ducic (2013). "Management of pathologic fractures of the mandible secondary to osteoradionecrosis." Otolaryngol Head Neck Surg 148(1): 54-58. Serafin, D., R. Riefkohl, I. Thomas and N. G. Georgiade (1980). "Vascularized ribperiosteal and osteocutaneous reconstruction of the maxilla and mandible: an assessment." Plast Reconstr Surg 66(5): 718-727. Store, G., M. Boysen and P. Skjelbred (2002). "Mandibular osteoradionecrosis: reconstructive surgery." Clin Otolaryngol Allied Sci 27(3): 197-203. Succo, G., M. Berrone, B. Battiston, P. Tos, F. Goia, P. Appendino and E. Crosetti (2014). "Step-by-step surgical technique for mandibular reconstruction with fibular free flap: application of digital technology in virtual surgical planning." Eur Arch Otorhinolaryngol. Suh, J. D., K. E. Blackwell, J. A. Sercarz, M. Cohen, J. H. Liu, C. G. Tang, E. Abemayor and V. Nabili (2010). "Disease relapse after segmental resection and free flap reconstruction for mandibular osteoradionecrosis." Otolaryngol Head Neck Surg 142(4): 586-591. Teng, M. S. and N. D. Futran (2005). "Osteoradionecrosis of the mandible." Curr Opin Otolaryngol Head Neck Surg 13(4): 217-221. Urken, M. L., D. Buchbinder, H. Weinberg, C. Vickery, A. Sheiner, R. Parker, J. Schaefer, P. Som, A. Shapiro, W. Lawson and et al. (1991). "Functional evaluation following microvascular oromandibular reconstruction of the oral cancer patient: a comparative study of reconstructed and nonreconstructed patients." Laryngoscope 101(9): 935-950. Vercruysse, H., Jr., T. Backer and M. Y. Mommaerts (2014). "Outcomes of osseous free flap reconstruction in stage III bisphosphonate-related osteonecrosis of the jaw: systematic review and a new case series." J Craniomaxillofac Surg 42(5): 377386. Wallace, C. G., Y. M. Chang, C. Y. Tsai and F. C. Wei (2010). "Harnessing the potential of the free fibula osteoseptocutaneous flap in mandible reconstruction." Plast Reconstr Surg 125(1): 305-314. Weaver, A. W. and D. B. Smith (1973). "Frozen autogenous mandibular stent-graft for immediate reconstruction in oral cancer surgery." Am J Surg 126(4): 505-506.
ACCEPTED MANUSCRIPT
RI PT
APPENDICES
Study Type
Continent
Total no. primary flaps
Flap Type
Mean Follow-up (months)
Retrospective Case Series
North America
63
Fibula n=38 (5 with pectoralis major, 6 with ALT, 1 with radial)
18.2
Europe
Cannady et al. (2011)
Retrospective Case Series
Celik et al. (2002)
Scapula n=1 Radial n=1
Rectus Abdominis n=7 Anterolateral thigh n=12 (2 with pectoralis major) Iliac crest n=63 (1 with ALT)
6
Fibula n=6
31.0
North America
53
Fibula n=36 Radial n=14 Rectus Abdominis n=1 Anterolateral thigh n=1 Iliac crest n=1
Not reported
Retrospective Case Series
Asia
27
Fibula n=22 Anterolateral thigh n=5
Not reported
Chandarana et al. (2013)
Retrospective Case Series
North America
12
Fibula n=4 Radial n=1 Scapula n=5 Iliac crest n=2
41.0
Chang et al. (2001)
Retrospective Case Series
30
Fibula n=17 Radial n=1 Scapula n=2 Rectus abdominis n=4 Iliac crest n=5
33.0
M AN U
Retrospective Case Series
TE D
Bozec et al. (2006)
SC
Author and Date Bauman et al. (2010)
EP
North America
Retrospective Case Series
South America
5
Fibula n=5
25.0
Retrospective Case Series
Europe
15
Latissimus Dorsi n=15
Not reported
Ioannides et al. (1993)
Retrospective Case Series
Europe
33
Serratus Anterior n=8 Iliac crest n=25
32.0
Militsakh et al. (2005)
Retrospective Case Series
North America
9
Radial n=9
36.0
Nakatsuka et al. (1996)
Retrospective Case Series
Asia
9
Radial n=1 Scapula n=8
Not reported
AC C
Curi et al. (2007) Hillerup et al. (2014)
ACCEPTED MANUSCRIPT
Retrospective Case Series
North America
12
Fibula n=12
45.0
Sawhney et al. (2013)
Retrospective Case Series
North America
37
Fibula n=32 Radial n=3 Scapula n=2
54.0
Store et al. (2002)
Retrospective Case Series
Europe
17
Fibula n=7 Radial n=1 Humerus n=5 Iliac crest n=4
57.0
Suh et al. (2010)
Retrospective Case Series
North America
40
Fibula n=36 Latissimus dorsi n=1 Serratus anterior n=2 Iliac crest n=1
17
M AN U
SC
RI PT
Santamaria et al. (1998)
AC C
EP
TE D
Table 1. Study characteristics
ACCEPTED MANUSCRIPT
63
Bozec et al. (2006) Cannady et al. (2011) Celik et al. (2002)
6
Type of Flap
Reason for Failure
4 (6.3)
Not stated
Vessel thrombosis (n=3) Carotid artery rupture (n=1)
0 (0)
N/A
7 (13.2)
Not stated Fibula n=2 Anterolateral thigh n=1
53 27 3 (11.1)
Chandarana et al. (2013) Chang et al. (2001)
13
4 (3.1) 30
AC C Store et al. (2002) Suh et al. (2010)
Not stated Fibula n=1 Iliac n=2 Scapula n=1 Fibula n=1 Latissimus Dorsi n=1
TE D
5 15
4 (1.4) 1 (20.0) 1 (6.7)
33
5 (15.2)
Iliac n=5
Fistula (n=3)
0 (0)
N/A
1 (11.1)
Scapula n=1
2 (16.7)
Fibula n=2
2 (5.4)
Fibula n=2
Not stated
Venous thrombosis (n=2), infection (n=1), other (n=1) Fistula (n=1) Plate exposure (n=1)
Venous thrombosis (n=4) Technical error (n=1)
9
EP
Curi et al. (2007) Hillerup et al. (2014) Ioannides et al. (1993) Militsakh et al. (2005) Nakatsuka et al. (1996) Santamaria et al. (1998) Sawhney et al. (2013)
RI PT
Bauman et al. (2010)
Total no. of free flap failures (%)
SC
Total free flaps (n)
M AN U
Study
9
12 37
17 40
Vessel thrombosis (n=1) Fistula (n=1) Skin paddle necrosis (n=2)
Infection (n=2) 2 (11.8)
Fibula n=2
0 (0)
N/A
Table 2. Free Flap Failures
ACCEPTED MANUSCRIPT
Baumann et al. (2010) (Baumann, Yu et al. 2011)
Total Flap Complications (n) 20
Bozec et al. (2006) (Bozec, Poissonnet et al. 2006) Cannady et al. (2011)
2
Celik et al. (2002) Chandarana et al. (2013)
3 20
Reason Infection (n=8) Fistula (n=6) Haematoma (n=2) Vessel Thrombosis (n=3) Vessel Rupture (n=1)
RI PT
Study
6
2
EP
Curi et al. (2007)
TE D
Chang et al. (2001)
M AN U
SC
13
Infection (n=1) Fistula (n=1) Skin paddle necrosis (n=1) Fistula (n=2) Vessel thrombosis (n=4) Vessel rupture (n=1) Other (n=5) Fistula (n=3) Infection (n=1) Skin paddle necrosis (n=1) Fistula (n=6) Non-union (n=4) Plate exposure (n=5) Haematoma (n=1) Other (n=3) Infection (n=1) Skin paddle necrosis (n=2) Vessel thrombosis (n=2) Fistula (n=1) Vessel thrombosis (n=1) N/A Infection (n=3) Fistula (n=2) Haematoma (n=2) Vessel Thrombosis (n=4) N/A Skin paddle necrosis (n=1) Fistula (n=1) Non-union (n=1) Skin paddle necrosis (n=1) Fistula (n=2) Vessel thrombosis (n=1) Skin paddle necrosis (n=1) Non-union (n=4)
AC C
Hillerup et al. (2014) Ioannides et al. (1993)
0 13
Militsakh et al. (2005) Nakatsuka et al. (1996)
0 3
Santamaria et al. (1998)
4
Sawhney et al. (2013)
15
ACCEPTED MANUSCRIPT
Plate exposure (n=3) 7 Infection (n=3) Plate exposure n=1 38 Infection n=7 Fistula n=6 Plate exposure n=17 Table 3. Free Flap Complications
Store et al. (2002)
AC C
EP
TE D
M AN U
SC
RI PT
Suh et al. (2010)
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT
Highlights
•
AC C
EP
TE D
M AN U
SC
• •
We conduct a worldwide systematic literature review of reported outcomes of microvascular free flap reconstruction in mandibular osteoradionecrosis. We examine the rates of free flap success and complications, and the different types of free flap tissue used. There is a significant failure and complication rate. There is a need for higher powered institutional studies to assess different types of free flap tissue and their use in mandibular reconstruction.
RI PT
•