Accepted Manuscript Pectoralis Major Myocutaneous Flap in Primary and Salvage Head and Neck Cancer Surgery Aleksandar Aničin, MD, PhD (consultant), Robert Šifrer, MD (consultant), Primož Strojan, MD, PhD, Professor PII:
S0278-2391(15)00600-X
DOI:
10.1016/j.joms.2015.05.016
Reference:
YJOMS 56824
To appear in:
Journal of Oral and Maxillofacial Surgery
Received Date: 21 April 2015 Revised Date:
10 May 2015
Accepted Date: 11 May 2015
Please cite this article as: Aničin A, Šifrer R, Strojan P, Pectoralis Major Myocutaneous Flap in Primary and Salvage Head and Neck Cancer Surgery, Journal of Oral and Maxillofacial Surgery (2015), doi: 10.1016/j.joms.2015.05.016. 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 Pectoralis Major Myocutaneous Flap in Primary and Salvage Head and Neck Cancer Surgery
Aleksandar Aničin, MD, PhD (consultant)
1
Robert Šifrer, MD (consultant)
2
Professor Primož Strojan, MD, PhD
1
Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre
SC
RI PT
1
Ljubljana, Slovenia
Department of Radiation Oncology, Institute of Oncology, Ljubljana, Slovenia
M AN U
2
Correspondence to: Alekasandar Aničin, MD, PhD
TE D
Department of Otorhinolaryngology and Cervicofacial Surgery University Medical Centre Ljubljana Zaloška 2, SI-1000 Ljubljana, Slovenia
EP
Phone: +386 1 5224850 Fax: +386 1 5224815
AC C
E-mail: [email protected]
ACCEPTED MANUSCRIPT Pectoralis Major Myocutaneous Flap in Primary and Salvage Head and Neck Cancer
AC C
EP
TE D
M AN U
SC
RI PT
Surgery
1
ACCEPTED MANUSCRIPT Abstract Purpose: To analyse the oncological, functional and aesthetic results of the pectoralis major myocutaneous flap (PMMF) used between November 2001 and April 2012 at the Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana,
RI PT
Slovenia.
Patients and Methods: Patients with squamous cell carcinoma of the head and neck (SCCHN) submitted to tissue defect reconstruction with PMMF were identified from a prospective
SC
database. Medical and surgical records were reviewed for information on clinical characteristics, treatment and outcome, and, specifically, indication for PMMF, wound
M AN U
healing, flap vitality, functional results and aesthetics.
Results: 40 PMMFs were used in 39 HNSCC patients. In respect to eventual previous therapy and prognosis, the patients were sorted into a primary surgery group (19 patients) and a salvage surgery group (20 patients with recurrent disease). Significantly better locoregional
TE D
control and disease-free survival were observed in the first group. Wound healing was completed in 32 patients (median time from surgery of 22 days). There were 3 cases with partial PMMF necrosis. Functional results, occlusion of pharyngocutaneous fistula, speech
groups.
EP
intelligibility, upper limb dysfunction, and aesthetic outcome did not differ between the two
AC C
Conclusion: PMMF is a reasonable choice in primary head and neck cancer surgery and in salvage procedures. Its use is characterised by vitality, reasonably short recovery time and a favourable aesthetic outcome at the donor site in the majority of patients.
2
ACCEPTED MANUSCRIPT Introduction In head and neck reconstructive surgery, selection of the most appropriate reconstruction method to fill a tissue defect after tumour resection follows the reconstructive ladder that leads from simple to more complex solutions. At the simpler part of this scale, regional flaps
RI PT
have proved to be reliable and easy to harvest, representing a good solution to cover larger tissue defects in the head and neck region. Among them, the most commonly used is pedicled pectoralis major myocutaneous flap (PMMF). Since 1979, when PMMF was first described
SC
by Ariyan, it has become “the workhorse” in head and neck cancer reconstructive surgery. PMMF can be easily mobilized and due to a rather long pedicle that includes the
M AN U
thoracoacromial artery as the axial vessel, it can even reach the level of the skull base. PMMF allows reconstruction immediately after resection through a single-stage procedure, which was not possible earlier with cutaneous tubulated flaps.1
A virtually simultaneous introduction of highly promising microvascular reconstructive
TE D
techniques, starting in 1981 with the description of the radial forearm free flap (RFFF),2 consigned PMMF to relative oblivion. Accordingly, the use of pedicled flaps was restricted only to cases of free-flap failure, salvage or reparative operations, where free flaps are
EP
generally not considered the most appropriate method due to tissue changes resulting from previous surgery and/or (chemo)radiotherapy, especially in co-morbid patients and at centres
AC C
with microsurgical facility shortage.3 Recently, several reports have testified to renewed interest in the use of PMMF in patients with squamous cell carcinoma of the head and neck (SCCHN), even in the centres where microvascular flaps are in routine use.4 This may be due to the growing interest in nonsurgical organ preservation treatment programs and, consequently, increasing need for salvage surgery, gaining ground for pedicled flaps.
3
ACCEPTED MANUSCRIPT In the present study, we analysed the oncological, functional and aesthetic results of the PMMF use during the last decade at the Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana, Slovenia.
RI PT
Methods
Due to the retrospective nature of this study, it was granted an exemption in writing by the Protocol Review Board of the University Clinical Centre Ljubljana, Slovenia.
SC
The database of the Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana was used to identify patients with SCCHN submitted to
M AN U
tissue defect reconstruction with PMMF between November 2001 and April 2012. The medical and surgical records of identified patients were reviewed for relevant information on clinical characteristics, treatment and outcome, and, specifically, indication for PMMF, wound healing, flap vitality, functional results and aesthetics. The tumours were staged using
TE D
criteria of the International Union against Cancer (UICC) TNM staging system, 7th edition. Details related to PMMF reconstruction, i.e. functionality, and aesthetics were provided only for patients who were alive and without locoregional recurrence at 6 months after
EP
surgery. Healing time and flap vitality were assessed in all patients. The healing time after PMMF surgery was measured from the day of operation to the day of completed wound
AC C
healing, which was defined by either continuation of oral feeding after oral, pharyngeal or laryngeal surgery or by removal of surgical stitches in the case of neck surgery. Depending on the indication for PMMF placement and its location, functionality was assessed in terms of pharyngocutaneous fistula (PCF) closure, restoration of oral alimentation and speech intelligibility. Considering the latter, a four-grade scale was used as described previously.5 Four aesthetic features at the donor site were considered: position of the nipple, bulk over the clavicle, depression in the upper chest because of pectoral major muscle transposition, and
4
ACCEPTED MANUSCRIPT appearance of the upper chest skin. When all four features were assessed as satisfying, the cosmetic effect was considered excellent; in other cases, it was deemed good (3 features recognised as satisfying) or poor ( 0.05) compared to those from the salvage surgery group.
Healing
RI PT
Healing process was successfully completed in 32 patients after a median time interval from surgery of 22 days (range 13-277 days). In six patients, local recurrence developed before surgical wound healing was accomplished (recurrence diagnosed at 120-301 days after
SC
PMMF surgery, median 165 days), and one patient died of sepsis 63 days after PCF occlusion without completion of the healing process. There was no statistically significant difference in
M AN U
the proportion of patients with an unhealed wound after PMMF surgery as well as in the duration of healing time between the primary and salvage surgery groups (Table 4).
Vitality
TE D
Vitality of the flap was not an issue in 37 of 40 PMMFs (92.5%). In one patient, a 50% necrosis of the PMMF developed, and the patient was taken for gastrostomy; local recurrence was diagnosed five months after PMMF surgery. In another two patients, a partial necrosis of
EP
the skin paddle was observed. Additional surgery employing anterolateral thigh free flap was successfully performed in one of them, whereas the second patient got a permanent
AC C
gastrostomy tube and died eight months after PMMF surgery with local recurrence and distant metastasis. All patients with partial flap necrosis belonged to the salvage surgery group (compared to the primary surgery group: p > 0.05) (Table 4).
Functionality Functional results are presented in Table 4.
8
ACCEPTED MANUSCRIPT Occlusion of the PCF. It was assessed in 9 patients: in 8 of them, fistula occlusion was observed after 16-122 days post-surgery (median 37.5 days), while in one patient, PCF persisted until his death due to local tumour recurrence 10 months after PMMF surgery. PCF occlusion time did not differ between the two surgical groups.
RI PT
Oral alimentation. It was sufficiently restored in 14 out of 15 patients with oral and/or pharyngeal resections without laryngectomy and in 11 out of 13 patients with laryngectomy followed by pharyngeal and/or pre-laryngeal cutaneous defect reconstruction or PCF
SC
occlusion. Three patients needed a permanent gastrostomy because of insufficient swallowing. After PMMF surgery, all patients with restored oral alimentation and free of disease or with
M AN U
metachronous malignant disease maintained constant body mass. Median time to restoration of oral alimentation was significantly shorter in the primary surgery group compared to the salvage surgery group (20.5 vs. 35 days, p = 0.046).
Speech intelligibility. After pharyngeal and oral reconstructions without laryngectomy,
TE D
spontaneous speech intelligibility was assessed as normal in 9 patients, mildly impaired in 4 patients and moderately impaired in 2 patients. After total laryngectomy-related PMMF reconstructions, oesophageal speech was compromised in 11 patients, and 2 patients were
patients.
EP
unable to learn any alternative speech. There was no difference between both groups of
AC C
Upper limb dysfunction. Due to major pectoral muscle transposition, no upper limb dysfunction interfering with everyday tasks was reported in our patients. Arm mobility in its extreme positions was limited due to spinal accessory nerve paresis in 4 patients who underwent classical radical neck dissection (with or without PMMF closure).
Aesthetics
9
ACCEPTED MANUSCRIPT Aesthetic effect was considered excellent in 26 patients and good in 5 patients (after extended RND, 3 patients had nipple displacement, and after PCF occlusion, 2 patients had residual bulkiness over the clavicle) (Fig. 1). No difference was observed between the two surgical
the PMMF tissue bulk next to tracheostoma after PCF occlusion.
Discussion
RI PT
groups (Table 4). In regard to the PMMF acceptor site, only one patient needed a reduction of
SC
PMMF proved to be one of the most versatile flaps in the reconstruction of tissue defects in head and neck cancer surgery. In the present study, the observed functional and aesthetic
M AN U
results were satisfactory to excellent, while survival statistics clearly reflected the timing of PMMF reconstruction.
As expected, the treatment outcome was influenced by eventual previous treatment intervention in the area of intended PMMF placement and by indication for surgery (i.e.
TE D
recurrent disease or other). The resulting fibrous changes and hypovascularity of the surgical bed are responsible for higher complication probability and reduced chance for complete tumour removal. In addition, there are reasons other than local failure that lead to poor
EP
survival in these patients, such as unhealthy lifestyle choices and propensity to systemic dissemination of tumour cells. In our patients, the LRC control was clearly superior in the
AC C
primary surgery group compared to the salvage surgery group. The difference in OS was less pronounced (at 2 years: 63% vs. 30%, p = 0.075), although still meaningful. Similarly, in a series of Zou et al., which included 28 patients with recurrent SCC of the oral cavity in whom PMMF was used for salvage reconstruction, the 3-year OS was only 30.9%.6 Despite unfavourable outcome results, surgical salvage is still the most effective curative-intent treatment of local or regional recurrence and should be offered to all patients with resectable disease and sufficiently good health status. The only alternative is re-irradiation alone or
10
ACCEPTED MANUSCRIPT combined with concurrent systemic therapy which resulted, even after the most rigorous selection of patients and with most advanced radiation techniques, in poor survival rates, ranging from 10 to 30% at 2 years.7,8 There were several favourable features of PMMF observed in our patients that should be
RI PT
mentioned. Firstly, the median time for the wound to heal was 20 days in 32 out of 39 patients; recurrence or death surpassed the completion of the healing process in 7 patients. Importantly, the healing time and frequency of unhealed wounds did not differ between the
was required in majority of patients after using PMMF.
SC
primary and salvage surgery groups. No delay in the commencement of adjuvant treatment
M AN U
Secondly, in our series, the incidence of partial flap necrosis was only 7.5% (3 cases, all belonging to the salvage surgery group). The figures reported in the literature vary between 429% for partial and 1-7% for total flap necrosis.9 The possible explanation for good vitality of skin paddles in our series could be their design. The horizontal bisection line placed at the
TE D
level of the nipple allows good vascularisation of a major part of the flap’s skin via direct perforating vessels from the pectoralis major muscle. Specifically, we place the incision for pectoralis major muscle exposition along with its lower edge, i.e. above the nipple in men and
EP
below the breast in women in order to maintain normal anatomic position of the nipple/breast, which also facilitates wound closure at the donor site. To the contrary, in a classic “defensive”
AC C
approach described by McGregor, the PMMF’s skin paddle is somewhat lower and includes fewer direct perforating arteries, as its preparation is done after raising a typical deltopectoral flap.10 The extension of the skin flap over the rectus sheath as the cause of skin flap necrosis, which can be minimized with modifications of the classic technique, was also identified by Ramakrishnan et al.11 From a functional point of view, upper limb dysfunction was observed only in 4 patients with spinal accessory nerve paresis caused by RND. Using the visual analogue scale (VAS)
11
ACCEPTED MANUSCRIPT evaluation, Montemari et al. also found no functional defects at the ipsilateral arm when PMMF was used for hypopharynx reconstruction, which could be attributed to good compensatory action of latissimus dorsi and teres major muscles.12. Furthermore, restoration of oral alimentation and normal to mildly impaired spontaneous speech intelligibility was
RI PT
recorded in 14 and 13 of our patients (out of 15), respectively, in whom pharyngeal and oral reconstruction, excluding laryngectomy, was performed. After total laryngectomy, 11 patients (out of 13) sufficiently restored the oral alimentation function and 11 patients had
SC
oesophageal speech, although compromised. Compared to anterolateral thigh free flap (ALTFF), Zhang et al. observed worse shoulder function but better speech function in patients
M AN U
reconstructed with PMMF when the University of Washington Quality of Life Questionnaire was used for evaluation.13
There is good evidence to support the routine use of a vascularised flap from outside the radiation field as a strategy to reduce the incidence of PCF after salvage total laryngectomy.14
TE D
On the other hand, vascularised tissue represents a fair option in post-laryngectomy PCF repair. We successfully used PMMF for the closure of extensive PCFs in 8 of 9 patients; the only patient with persistent PCF died of local recurrence at 10 months after PMMF surgery.
EP
With a median PCF occlusion time of 37.5 days (range 16-122 days), PMMF can be considered a good reconstruction tool in this setting, particularly in heavily pre-treated
AC C
patients. Finally, aesthetic results in our series were also favourable and consistent with other reports.12
Apparently, the choice of the most appropriate reconstructive method is of crucial importance. Although clinical practice militates in favour of better durability of pedicled flaps compared to microvascular ones, especially in patients with severe co-morbidities, prior to (chemo)radiotherapy or surgery in areas exposed to saliva, virtually no references can be found to confirm this. Our experience with PMMF, supported by statistics from large
12
ACCEPTED MANUSCRIPT series,4,15,16 confirmed its vitality, a reasonably short recovery time and a favourable aesthetic outcome at the donor site in the majority of patients. We can conclude that there are still vital indications for PMMF even in the era of microvascular free flap reconstruction. According to our experience, PMMF is a reasonable
RI PT
choice in primary head and neck cancer surgery whenever comparable functional and aesthetic results are expected, as in the case of microvascular flaps, e.g. in the reconstruction of the lateral pharyngeal wall and tongue. In salvage procedures, indications for pedicled flaps
SC
are much wider and also include RND or pharyngeal reconstruction after circumferential
AC C
EP
TE D
choice reconstructive method.
M AN U
pharyngolaryngectomy, while in sealing persistent PCFs after laryngectomy, PMMF is a first-
13
ACCEPTED MANUSCRIPT References 1. Ariyan S: The pectoralis major myocutaneous flap. A versatile flap for reconstruction in the head and neck. Plast Reconstr Surg 63:73–81, 1979
61:139-141, 1981
RI PT
2. Yang G, Chen B, Gao W, et al: Forearm free skin flap transplantation. Natl Med J China
3. El-Marakby HH: The reliability of pectoralis major myocutaneous flap in head and neck reconstruction. J Egypt Natl Canc Inst 18:41-50, 2006
SC
4. Milenović A, Virag M, Uglesić V, Aljinović-Ratković N: The pectoralis major flap in head and neck reconstruction: first 500 patients. J Craniomaxillofac Surg 34:340-343,
M AN U
2006
5. De Carvaho-Teles V, Sennes LU, Gielow I: Speech evaluation after palatal augmentation in patients undergoing glossectomy. Arch Otolaryngol Head Neck Surg 134:1066-1070, 2008
TE D
6. Zou H, Zhang WF, Han QB, Zhao YF: Salvage reconstruction of extensive recurrent oral cancer defects with the pectoralis major myocutaneous flap. J Oral Maxillofac Surg 65:1935-1939, 2007
EP
7. Strojan P, Corry J, Eisbruch A, et al: Recurrent and second primary squamous cell carcinoma of the head and neck: when and how to reirradiate. Head Neck 37:134-150,
AC C
2015
8. Gomez-Millan J, Fernandez RJ, Medina Carmona JA: Current status of IMRT in head and neck cancer. Rep Pract Oncol Radiother 18:371-375, 2013 9. Castelli ML, Pecorari G, Succo G, Bena A, Andreis M, Sartoris A: Pectoralis major myocutaneous flap: analysis of complications in difficult patients. Eur Arch Otorhinolaryngol 258:542-545, 2001
14
ACCEPTED MANUSCRIPT 10. McGregor I: A “defensive” approach to the island pectoralis major myocutaneous flap. Br J Plast Surg 34:435-437, 1981 11. Ramakrishnan V, Yao W, Campana J: Improved skin paddle survival in pectoralis major myocutaneous flap reconstruction of head and neck defects. Arch Facial Plast Surg
RI PT
11:306-310, 2009
12. Montemari G, Rocco A, Galla S, Damiani V, Bellocchi G: Hypopharynx reconstruction with pectoralis major myofascial flap: our experience in 45 cases. Acta Otorhinolaryngol
SC
Ital 32:93–97, 2012
13. Zhang X, Li MJ, Fang QG, Sun CF: A comparison between the pectoralis major
M AN U
myocutaneous flap and the free anterolateral thigh perforator flap for reconstruction in head and neck cancer patients: assessment of the quality of life. J Craniofac Surg 25:868871, 2014
14. Paleri V, Drinnan M, van den Brekel MW, et al: Vascularised tissue to reduce fistula
2014
TE D
following salvage total laryngectomy: a systematic review. Laryngoscope 124:1848-1853,
15. Liu R. Gullane P. Brown D. Irish J: Pectoralis major myocutaneous pedicled flap in head
EP
and neck reconstruction: retrospective review of indications and results in 244 consecutive cases at the Toronto General Hospital. J Otolaryngol 30:34-40, 2001
AC C
16. Avery C: A perspective on the role of the pectoralis major flap in oral and maxillofacial oncology surgery. Oral Surgery 7:130-142, 2014
15
ACCEPTED MANUSCRIPT Figure legend Fig. 1. PMMF donor site in two patients from the primary surgery group showing an excellent
AC C
EP
TE D
M AN U
SC
RI PT
aesthetics effect: A – 65 months after reconstruction; B – 68 months after reconstruction.
16
ACCEPTED MANUSCRIPT Table 1. Characteristics of patients, tumors and treatment. p-value
2/37 60 (40-76)
Salvage surgery (N=20) 1/19 61 (52-76)
1 (2.6%) 20 (51.2%) 16 (41%) 2 (5.2%)
1 (5.3%) 10 (52.6%) 6 (31.6%) 2 (10.5%)
0 10 (50%) 10 (50%) 0
n.s.
5 (12.8%) 17 (43.5%) 6 (15.5%) 10 (25.6%) 1 (2.6%)
1 (5.3%) 9 (47.4%) 5 (26.3%) 3 (15.8%) 1 (5.25%)
4 (20%) 8 (40%) 1 (5%) 7 (35%) 0
0.079
1 (2.6%) 9 (23%) 29 (74.4%) IVa=22 IVb=6 IVc=1
1 (5.25%) 6 (31.6%) 12 (63.15%) IVa=9 IVb=3 IVc=0
0 3 (15%) 17 (85%) IVa=13 IVb=3 IVc=1
n.s.
AC C
EP
TE D
Indication for PMMF PCF occlusion 10 (25.7%) 5 (26.3%) 5 (25%) Pharyngeal/oral defects, without 15 (38.5%) 9 (47.4%) 6 (30%) laryngectomy) Defects after extended laryngectomy 9 (23%) 3 (15.8%) 6 (30%) Defects after extended RND 5 (12.8%) 2 (10.5%) 3 (15%) Therapy before PMMF surgery No 15 (38.5%) 15 (79%) 0 Surgery 1 (2.6%) 0 1 (5%) Surgery + radiotherapy 8 (20.5%) 4 (21%) 4 (20%) Radiotherapy 8 (20.5%) 0 7 (35%) Radiochemotherapy 7 (18%) 0 8 (40%) Adjuvant treatment after PMMF surgery No 23 (59%) 4 (21.1%) 19 (95 %) Radiotherapy 9 (23%) 7 (36.1%) 1 (5%) Chemoradioherapy 7 (18%) 8 (42.1%) 0 2 Extracapsular tumour spread Positive 12 (55%) 7 (54%) 5 (55.5%) Negative 10 (45%) 6 (46%) 4 (44.5%) 1 Median (range), in years. 2 Only patients with pN+, N=22 PMMF – Pectoralis major myocutaneous flap; ASA – American Society of Anesthesiologists; n.s. – Statistically non-significant; N – Number of patients.
17
n.s. n.s.
RI PT
Sex (female/male) Age(years)1 Performance status (ASA score): ASA 1 ASA 2 ASA 3 ASA 4 Primary tumour site Oral cavity Oropharynx Hypopharynx Larynx Unknown primary Overall pTNM stage Stage II Stage III Stage IV
Primary surgery (N=19) 1/18 60 (40-75)
SC
All (N=39)
M AN U
Patients
n.s.
S0278-2391(15)00600-X
DOI:
10.1016/j.joms.2015.05.016
Reference:
YJOMS 56824
To appear in:
Journal of Oral and Maxillofacial Surgery
Received Date: 21 April 2015 Revised Date:
10 May 2015
Accepted Date: 11 May 2015
Please cite this article as: Aničin A, Šifrer R, Strojan P, Pectoralis Major Myocutaneous Flap in Primary and Salvage Head and Neck Cancer Surgery, Journal of Oral and Maxillofacial Surgery (2015), doi: 10.1016/j.joms.2015.05.016. 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 Pectoralis Major Myocutaneous Flap in Primary and Salvage Head and Neck Cancer Surgery
Aleksandar Aničin, MD, PhD (consultant)
1
Robert Šifrer, MD (consultant)
2
Professor Primož Strojan, MD, PhD
1
Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre
SC
RI PT
1
Ljubljana, Slovenia
Department of Radiation Oncology, Institute of Oncology, Ljubljana, Slovenia
M AN U
2
Correspondence to: Alekasandar Aničin, MD, PhD
TE D
Department of Otorhinolaryngology and Cervicofacial Surgery University Medical Centre Ljubljana Zaloška 2, SI-1000 Ljubljana, Slovenia
EP
Phone: +386 1 5224850 Fax: +386 1 5224815
AC C
E-mail: [email protected]
ACCEPTED MANUSCRIPT Pectoralis Major Myocutaneous Flap in Primary and Salvage Head and Neck Cancer
AC C
EP
TE D
M AN U
SC
RI PT
Surgery
1
ACCEPTED MANUSCRIPT Abstract Purpose: To analyse the oncological, functional and aesthetic results of the pectoralis major myocutaneous flap (PMMF) used between November 2001 and April 2012 at the Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana,
RI PT
Slovenia.
Patients and Methods: Patients with squamous cell carcinoma of the head and neck (SCCHN) submitted to tissue defect reconstruction with PMMF were identified from a prospective
SC
database. Medical and surgical records were reviewed for information on clinical characteristics, treatment and outcome, and, specifically, indication for PMMF, wound
M AN U
healing, flap vitality, functional results and aesthetics.
Results: 40 PMMFs were used in 39 HNSCC patients. In respect to eventual previous therapy and prognosis, the patients were sorted into a primary surgery group (19 patients) and a salvage surgery group (20 patients with recurrent disease). Significantly better locoregional
TE D
control and disease-free survival were observed in the first group. Wound healing was completed in 32 patients (median time from surgery of 22 days). There were 3 cases with partial PMMF necrosis. Functional results, occlusion of pharyngocutaneous fistula, speech
groups.
EP
intelligibility, upper limb dysfunction, and aesthetic outcome did not differ between the two
AC C
Conclusion: PMMF is a reasonable choice in primary head and neck cancer surgery and in salvage procedures. Its use is characterised by vitality, reasonably short recovery time and a favourable aesthetic outcome at the donor site in the majority of patients.
2
ACCEPTED MANUSCRIPT Introduction In head and neck reconstructive surgery, selection of the most appropriate reconstruction method to fill a tissue defect after tumour resection follows the reconstructive ladder that leads from simple to more complex solutions. At the simpler part of this scale, regional flaps
RI PT
have proved to be reliable and easy to harvest, representing a good solution to cover larger tissue defects in the head and neck region. Among them, the most commonly used is pedicled pectoralis major myocutaneous flap (PMMF). Since 1979, when PMMF was first described
SC
by Ariyan, it has become “the workhorse” in head and neck cancer reconstructive surgery. PMMF can be easily mobilized and due to a rather long pedicle that includes the
M AN U
thoracoacromial artery as the axial vessel, it can even reach the level of the skull base. PMMF allows reconstruction immediately after resection through a single-stage procedure, which was not possible earlier with cutaneous tubulated flaps.1
A virtually simultaneous introduction of highly promising microvascular reconstructive
TE D
techniques, starting in 1981 with the description of the radial forearm free flap (RFFF),2 consigned PMMF to relative oblivion. Accordingly, the use of pedicled flaps was restricted only to cases of free-flap failure, salvage or reparative operations, where free flaps are
EP
generally not considered the most appropriate method due to tissue changes resulting from previous surgery and/or (chemo)radiotherapy, especially in co-morbid patients and at centres
AC C
with microsurgical facility shortage.3 Recently, several reports have testified to renewed interest in the use of PMMF in patients with squamous cell carcinoma of the head and neck (SCCHN), even in the centres where microvascular flaps are in routine use.4 This may be due to the growing interest in nonsurgical organ preservation treatment programs and, consequently, increasing need for salvage surgery, gaining ground for pedicled flaps.
3
ACCEPTED MANUSCRIPT In the present study, we analysed the oncological, functional and aesthetic results of the PMMF use during the last decade at the Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana, Slovenia.
RI PT
Methods
Due to the retrospective nature of this study, it was granted an exemption in writing by the Protocol Review Board of the University Clinical Centre Ljubljana, Slovenia.
SC
The database of the Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana was used to identify patients with SCCHN submitted to
M AN U
tissue defect reconstruction with PMMF between November 2001 and April 2012. The medical and surgical records of identified patients were reviewed for relevant information on clinical characteristics, treatment and outcome, and, specifically, indication for PMMF, wound healing, flap vitality, functional results and aesthetics. The tumours were staged using
TE D
criteria of the International Union against Cancer (UICC) TNM staging system, 7th edition. Details related to PMMF reconstruction, i.e. functionality, and aesthetics were provided only for patients who were alive and without locoregional recurrence at 6 months after
EP
surgery. Healing time and flap vitality were assessed in all patients. The healing time after PMMF surgery was measured from the day of operation to the day of completed wound
AC C
healing, which was defined by either continuation of oral feeding after oral, pharyngeal or laryngeal surgery or by removal of surgical stitches in the case of neck surgery. Depending on the indication for PMMF placement and its location, functionality was assessed in terms of pharyngocutaneous fistula (PCF) closure, restoration of oral alimentation and speech intelligibility. Considering the latter, a four-grade scale was used as described previously.5 Four aesthetic features at the donor site were considered: position of the nipple, bulk over the clavicle, depression in the upper chest because of pectoral major muscle transposition, and
4
ACCEPTED MANUSCRIPT appearance of the upper chest skin. When all four features were assessed as satisfying, the cosmetic effect was considered excellent; in other cases, it was deemed good (3 features recognised as satisfying) or poor ( 0.05) compared to those from the salvage surgery group.
Healing
RI PT
Healing process was successfully completed in 32 patients after a median time interval from surgery of 22 days (range 13-277 days). In six patients, local recurrence developed before surgical wound healing was accomplished (recurrence diagnosed at 120-301 days after
SC
PMMF surgery, median 165 days), and one patient died of sepsis 63 days after PCF occlusion without completion of the healing process. There was no statistically significant difference in
M AN U
the proportion of patients with an unhealed wound after PMMF surgery as well as in the duration of healing time between the primary and salvage surgery groups (Table 4).
Vitality
TE D
Vitality of the flap was not an issue in 37 of 40 PMMFs (92.5%). In one patient, a 50% necrosis of the PMMF developed, and the patient was taken for gastrostomy; local recurrence was diagnosed five months after PMMF surgery. In another two patients, a partial necrosis of
EP
the skin paddle was observed. Additional surgery employing anterolateral thigh free flap was successfully performed in one of them, whereas the second patient got a permanent
AC C
gastrostomy tube and died eight months after PMMF surgery with local recurrence and distant metastasis. All patients with partial flap necrosis belonged to the salvage surgery group (compared to the primary surgery group: p > 0.05) (Table 4).
Functionality Functional results are presented in Table 4.
8
ACCEPTED MANUSCRIPT Occlusion of the PCF. It was assessed in 9 patients: in 8 of them, fistula occlusion was observed after 16-122 days post-surgery (median 37.5 days), while in one patient, PCF persisted until his death due to local tumour recurrence 10 months after PMMF surgery. PCF occlusion time did not differ between the two surgical groups.
RI PT
Oral alimentation. It was sufficiently restored in 14 out of 15 patients with oral and/or pharyngeal resections without laryngectomy and in 11 out of 13 patients with laryngectomy followed by pharyngeal and/or pre-laryngeal cutaneous defect reconstruction or PCF
SC
occlusion. Three patients needed a permanent gastrostomy because of insufficient swallowing. After PMMF surgery, all patients with restored oral alimentation and free of disease or with
M AN U
metachronous malignant disease maintained constant body mass. Median time to restoration of oral alimentation was significantly shorter in the primary surgery group compared to the salvage surgery group (20.5 vs. 35 days, p = 0.046).
Speech intelligibility. After pharyngeal and oral reconstructions without laryngectomy,
TE D
spontaneous speech intelligibility was assessed as normal in 9 patients, mildly impaired in 4 patients and moderately impaired in 2 patients. After total laryngectomy-related PMMF reconstructions, oesophageal speech was compromised in 11 patients, and 2 patients were
patients.
EP
unable to learn any alternative speech. There was no difference between both groups of
AC C
Upper limb dysfunction. Due to major pectoral muscle transposition, no upper limb dysfunction interfering with everyday tasks was reported in our patients. Arm mobility in its extreme positions was limited due to spinal accessory nerve paresis in 4 patients who underwent classical radical neck dissection (with or without PMMF closure).
Aesthetics
9
ACCEPTED MANUSCRIPT Aesthetic effect was considered excellent in 26 patients and good in 5 patients (after extended RND, 3 patients had nipple displacement, and after PCF occlusion, 2 patients had residual bulkiness over the clavicle) (Fig. 1). No difference was observed between the two surgical
the PMMF tissue bulk next to tracheostoma after PCF occlusion.
Discussion
RI PT
groups (Table 4). In regard to the PMMF acceptor site, only one patient needed a reduction of
SC
PMMF proved to be one of the most versatile flaps in the reconstruction of tissue defects in head and neck cancer surgery. In the present study, the observed functional and aesthetic
M AN U
results were satisfactory to excellent, while survival statistics clearly reflected the timing of PMMF reconstruction.
As expected, the treatment outcome was influenced by eventual previous treatment intervention in the area of intended PMMF placement and by indication for surgery (i.e.
TE D
recurrent disease or other). The resulting fibrous changes and hypovascularity of the surgical bed are responsible for higher complication probability and reduced chance for complete tumour removal. In addition, there are reasons other than local failure that lead to poor
EP
survival in these patients, such as unhealthy lifestyle choices and propensity to systemic dissemination of tumour cells. In our patients, the LRC control was clearly superior in the
AC C
primary surgery group compared to the salvage surgery group. The difference in OS was less pronounced (at 2 years: 63% vs. 30%, p = 0.075), although still meaningful. Similarly, in a series of Zou et al., which included 28 patients with recurrent SCC of the oral cavity in whom PMMF was used for salvage reconstruction, the 3-year OS was only 30.9%.6 Despite unfavourable outcome results, surgical salvage is still the most effective curative-intent treatment of local or regional recurrence and should be offered to all patients with resectable disease and sufficiently good health status. The only alternative is re-irradiation alone or
10
ACCEPTED MANUSCRIPT combined with concurrent systemic therapy which resulted, even after the most rigorous selection of patients and with most advanced radiation techniques, in poor survival rates, ranging from 10 to 30% at 2 years.7,8 There were several favourable features of PMMF observed in our patients that should be
RI PT
mentioned. Firstly, the median time for the wound to heal was 20 days in 32 out of 39 patients; recurrence or death surpassed the completion of the healing process in 7 patients. Importantly, the healing time and frequency of unhealed wounds did not differ between the
was required in majority of patients after using PMMF.
SC
primary and salvage surgery groups. No delay in the commencement of adjuvant treatment
M AN U
Secondly, in our series, the incidence of partial flap necrosis was only 7.5% (3 cases, all belonging to the salvage surgery group). The figures reported in the literature vary between 429% for partial and 1-7% for total flap necrosis.9 The possible explanation for good vitality of skin paddles in our series could be their design. The horizontal bisection line placed at the
TE D
level of the nipple allows good vascularisation of a major part of the flap’s skin via direct perforating vessels from the pectoralis major muscle. Specifically, we place the incision for pectoralis major muscle exposition along with its lower edge, i.e. above the nipple in men and
EP
below the breast in women in order to maintain normal anatomic position of the nipple/breast, which also facilitates wound closure at the donor site. To the contrary, in a classic “defensive”
AC C
approach described by McGregor, the PMMF’s skin paddle is somewhat lower and includes fewer direct perforating arteries, as its preparation is done after raising a typical deltopectoral flap.10 The extension of the skin flap over the rectus sheath as the cause of skin flap necrosis, which can be minimized with modifications of the classic technique, was also identified by Ramakrishnan et al.11 From a functional point of view, upper limb dysfunction was observed only in 4 patients with spinal accessory nerve paresis caused by RND. Using the visual analogue scale (VAS)
11
ACCEPTED MANUSCRIPT evaluation, Montemari et al. also found no functional defects at the ipsilateral arm when PMMF was used for hypopharynx reconstruction, which could be attributed to good compensatory action of latissimus dorsi and teres major muscles.12. Furthermore, restoration of oral alimentation and normal to mildly impaired spontaneous speech intelligibility was
RI PT
recorded in 14 and 13 of our patients (out of 15), respectively, in whom pharyngeal and oral reconstruction, excluding laryngectomy, was performed. After total laryngectomy, 11 patients (out of 13) sufficiently restored the oral alimentation function and 11 patients had
SC
oesophageal speech, although compromised. Compared to anterolateral thigh free flap (ALTFF), Zhang et al. observed worse shoulder function but better speech function in patients
M AN U
reconstructed with PMMF when the University of Washington Quality of Life Questionnaire was used for evaluation.13
There is good evidence to support the routine use of a vascularised flap from outside the radiation field as a strategy to reduce the incidence of PCF after salvage total laryngectomy.14
TE D
On the other hand, vascularised tissue represents a fair option in post-laryngectomy PCF repair. We successfully used PMMF for the closure of extensive PCFs in 8 of 9 patients; the only patient with persistent PCF died of local recurrence at 10 months after PMMF surgery.
EP
With a median PCF occlusion time of 37.5 days (range 16-122 days), PMMF can be considered a good reconstruction tool in this setting, particularly in heavily pre-treated
AC C
patients. Finally, aesthetic results in our series were also favourable and consistent with other reports.12
Apparently, the choice of the most appropriate reconstructive method is of crucial importance. Although clinical practice militates in favour of better durability of pedicled flaps compared to microvascular ones, especially in patients with severe co-morbidities, prior to (chemo)radiotherapy or surgery in areas exposed to saliva, virtually no references can be found to confirm this. Our experience with PMMF, supported by statistics from large
12
ACCEPTED MANUSCRIPT series,4,15,16 confirmed its vitality, a reasonably short recovery time and a favourable aesthetic outcome at the donor site in the majority of patients. We can conclude that there are still vital indications for PMMF even in the era of microvascular free flap reconstruction. According to our experience, PMMF is a reasonable
RI PT
choice in primary head and neck cancer surgery whenever comparable functional and aesthetic results are expected, as in the case of microvascular flaps, e.g. in the reconstruction of the lateral pharyngeal wall and tongue. In salvage procedures, indications for pedicled flaps
SC
are much wider and also include RND or pharyngeal reconstruction after circumferential
AC C
EP
TE D
choice reconstructive method.
M AN U
pharyngolaryngectomy, while in sealing persistent PCFs after laryngectomy, PMMF is a first-
13
ACCEPTED MANUSCRIPT References 1. Ariyan S: The pectoralis major myocutaneous flap. A versatile flap for reconstruction in the head and neck. Plast Reconstr Surg 63:73–81, 1979
61:139-141, 1981
RI PT
2. Yang G, Chen B, Gao W, et al: Forearm free skin flap transplantation. Natl Med J China
3. El-Marakby HH: The reliability of pectoralis major myocutaneous flap in head and neck reconstruction. J Egypt Natl Canc Inst 18:41-50, 2006
SC
4. Milenović A, Virag M, Uglesić V, Aljinović-Ratković N: The pectoralis major flap in head and neck reconstruction: first 500 patients. J Craniomaxillofac Surg 34:340-343,
M AN U
2006
5. De Carvaho-Teles V, Sennes LU, Gielow I: Speech evaluation after palatal augmentation in patients undergoing glossectomy. Arch Otolaryngol Head Neck Surg 134:1066-1070, 2008
TE D
6. Zou H, Zhang WF, Han QB, Zhao YF: Salvage reconstruction of extensive recurrent oral cancer defects with the pectoralis major myocutaneous flap. J Oral Maxillofac Surg 65:1935-1939, 2007
EP
7. Strojan P, Corry J, Eisbruch A, et al: Recurrent and second primary squamous cell carcinoma of the head and neck: when and how to reirradiate. Head Neck 37:134-150,
AC C
2015
8. Gomez-Millan J, Fernandez RJ, Medina Carmona JA: Current status of IMRT in head and neck cancer. Rep Pract Oncol Radiother 18:371-375, 2013 9. Castelli ML, Pecorari G, Succo G, Bena A, Andreis M, Sartoris A: Pectoralis major myocutaneous flap: analysis of complications in difficult patients. Eur Arch Otorhinolaryngol 258:542-545, 2001
14
ACCEPTED MANUSCRIPT 10. McGregor I: A “defensive” approach to the island pectoralis major myocutaneous flap. Br J Plast Surg 34:435-437, 1981 11. Ramakrishnan V, Yao W, Campana J: Improved skin paddle survival in pectoralis major myocutaneous flap reconstruction of head and neck defects. Arch Facial Plast Surg
RI PT
11:306-310, 2009
12. Montemari G, Rocco A, Galla S, Damiani V, Bellocchi G: Hypopharynx reconstruction with pectoralis major myofascial flap: our experience in 45 cases. Acta Otorhinolaryngol
SC
Ital 32:93–97, 2012
13. Zhang X, Li MJ, Fang QG, Sun CF: A comparison between the pectoralis major
M AN U
myocutaneous flap and the free anterolateral thigh perforator flap for reconstruction in head and neck cancer patients: assessment of the quality of life. J Craniofac Surg 25:868871, 2014
14. Paleri V, Drinnan M, van den Brekel MW, et al: Vascularised tissue to reduce fistula
2014
TE D
following salvage total laryngectomy: a systematic review. Laryngoscope 124:1848-1853,
15. Liu R. Gullane P. Brown D. Irish J: Pectoralis major myocutaneous pedicled flap in head
EP
and neck reconstruction: retrospective review of indications and results in 244 consecutive cases at the Toronto General Hospital. J Otolaryngol 30:34-40, 2001
AC C
16. Avery C: A perspective on the role of the pectoralis major flap in oral and maxillofacial oncology surgery. Oral Surgery 7:130-142, 2014
15
ACCEPTED MANUSCRIPT Figure legend Fig. 1. PMMF donor site in two patients from the primary surgery group showing an excellent
AC C
EP
TE D
M AN U
SC
RI PT
aesthetics effect: A – 65 months after reconstruction; B – 68 months after reconstruction.
16
ACCEPTED MANUSCRIPT Table 1. Characteristics of patients, tumors and treatment. p-value
2/37 60 (40-76)
Salvage surgery (N=20) 1/19 61 (52-76)
1 (2.6%) 20 (51.2%) 16 (41%) 2 (5.2%)
1 (5.3%) 10 (52.6%) 6 (31.6%) 2 (10.5%)
0 10 (50%) 10 (50%) 0
n.s.
5 (12.8%) 17 (43.5%) 6 (15.5%) 10 (25.6%) 1 (2.6%)
1 (5.3%) 9 (47.4%) 5 (26.3%) 3 (15.8%) 1 (5.25%)
4 (20%) 8 (40%) 1 (5%) 7 (35%) 0
0.079
1 (2.6%) 9 (23%) 29 (74.4%) IVa=22 IVb=6 IVc=1
1 (5.25%) 6 (31.6%) 12 (63.15%) IVa=9 IVb=3 IVc=0
0 3 (15%) 17 (85%) IVa=13 IVb=3 IVc=1
n.s.
AC C
EP
TE D
Indication for PMMF PCF occlusion 10 (25.7%) 5 (26.3%) 5 (25%) Pharyngeal/oral defects, without 15 (38.5%) 9 (47.4%) 6 (30%) laryngectomy) Defects after extended laryngectomy 9 (23%) 3 (15.8%) 6 (30%) Defects after extended RND 5 (12.8%) 2 (10.5%) 3 (15%) Therapy before PMMF surgery No 15 (38.5%) 15 (79%) 0 Surgery 1 (2.6%) 0 1 (5%) Surgery + radiotherapy 8 (20.5%) 4 (21%) 4 (20%) Radiotherapy 8 (20.5%) 0 7 (35%) Radiochemotherapy 7 (18%) 0 8 (40%) Adjuvant treatment after PMMF surgery No 23 (59%) 4 (21.1%) 19 (95 %) Radiotherapy 9 (23%) 7 (36.1%) 1 (5%) Chemoradioherapy 7 (18%) 8 (42.1%) 0 2 Extracapsular tumour spread Positive 12 (55%) 7 (54%) 5 (55.5%) Negative 10 (45%) 6 (46%) 4 (44.5%) 1 Median (range), in years. 2 Only patients with pN+, N=22 PMMF – Pectoralis major myocutaneous flap; ASA – American Society of Anesthesiologists; n.s. – Statistically non-significant; N – Number of patients.
17
n.s. n.s.
RI PT
Sex (female/male) Age(years)1 Performance status (ASA score): ASA 1 ASA 2 ASA 3 ASA 4 Primary tumour site Oral cavity Oropharynx Hypopharynx Larynx Unknown primary Overall pTNM stage Stage II Stage III Stage IV
Primary surgery (N=19) 1/18 60 (40-75)
SC
All (N=39)
M AN U
Patients
n.s.
