Eur Arch Otorhinolaryngol DOI 10.1007/s00405-014-3372-0
HEAD AND NECK
Risk factors of recipient site infection in head and neck cancer patients undergoing pectoralis major myocutaneous flap reconstruction Chao-Hsien Wang • Yong-Kie Wong • Ching-Ping Wang • Chen-Chi Wang • Rong-San Jiang • Chih-Sheng Lai • Shih-An Liu
Received: 29 July 2014 / Accepted: 22 October 2014 Ó Springer-Verlag Berlin Heidelberg 2014
Abstract The aim of this study was to investigate the factors associated with infection at the recipient site of pectoralis major myocutaneous flap (PMMF) of head and neck cancer patients. We retrospectively reviewed head and neck cancer patients who underwent PMMF reconstruction and identified those with recipient site infection. Variables of patients with and without infection were compared and associated factors were investigated by logistic regression model. A total of 478 patients were included in the final analysis and 183 patients (38.3 %) developed recipient site infection. Lower margin of skin island, concurrent tracheotomy, diabetes mellitus, mandibular plate reconstruction, prior radiation, and perioperative blood transfusion were independent factors associated with recipient site infection of PMMF. Skin island of PMMF beyond the eighth intercostal space markedly increased the risk of recipient site infection after major head and neck cancer surgery. Recognition of
C.-H. Wang C.-P. Wang C.-C. Wang R.-S. Jiang S.-A. Liu (&) Department of Otolaryngology, Taichung Veterans General Hospital, No. 1650, Sect 4, Taiwan Boulevard, Taichung, Taiwan e-mail: [email protected] Y.-K. Wong Department of Oral and Maxillofacial Surgery, Taichung Veterans General Hospital, Taichung, Taiwan C.-S. Lai Department of Plastic and Reconstructive Surgery, Taichung Veterans General Hospital, Taichung, Taiwan S.-A. Liu Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
relevant factors associated with infection may help surgeons to identify those at risk. Keywords Head neck cancer Pectoralis major myocutaneous flap Surgical site infection Radiation Logistic regression model
Introduction The pectoralis major myocutaneous flap (PMMF), which gets its blood supply mainly from the thoracoacromial artery, was first introduced in 1979 by Ariyan [1]. PMMF is recognized as one of the most important techniques in the reconstruction of major head and neck cancer surgery due to its simple technical aspects, versatility, and proximity to the head and neck region [2]. Although the increased popularity of free flap reconstruction in complex soft tissue with/without bony defect has somewhat surpassed the PMMF, it is still a very valuable and reliable reconstructive method for defect after extirpation of head and neck cancer [3]. The complication rates of PMMF were reported to range from 13 to 43 % in the literature [3–8]. Complications consisted of infection, wound dehiscence, fistula formation, seroma, hematoma, and flap necrosis [7]. Factors associated with higher complication rates included salvage procedures, number of pack-years of cigarettes smoked, oral cavity reconstructions [2, 5], age over 70, female gender, albumin \4 g/dL [5], number of comorbidities [2, 5, 6], prior radiation therapy [3, 6, 9], prior chemotherapy, bipedicled flaps [6], extension of the skin flap over the rectus sheath [8], hypopharyngeal defect [9, 10], and concurrent anterior mandibular plate reconstruction [11]. However, fewer studies have investigated recipient site infection of
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PMMF and the relationship between lower margin of PMMF skin island and complications. Therefore, the aim of this study was to investigate the rate of recipient site infection after PMMF reconstruction in a large cohort of head and neck cancer patients. Furthermore, we determined the associated factors of recipient site infection after PMMF reconstruction by logistic regression analyses.
logistic regression analysis were excluded for further logistic regression model. Finally, the logistic regression model was adjusted for age. All statistical analyses were performed using SPSS for Windows, version 12.1 (SPSS, Chicago, IL, USA), and a P value \0.05 was regarded as statistically significant.
Results Materials and methods This study protocol was approved by the Institutional Review Board of Taichung Veterans General Hospital. We retrospectively reviewed over 2,000 chart records of head and neck cancer patients receiving surgical intervention in the studied hospital from March 1994 to December 2012. Those who underwent PMMF reconstruction were eligible for the current study. Those who had received other flap reconstruction simultaneously or had inadequate chart records were excluded. All patients were restaged according to the guidelines of the American Joint Committee on Cancer. Patients with stage I or II diseases were regarded as early stage, whereas those with stage III or IV were defined as late stage. Basic demographic data including age, gender, and personal habits such as smoking, alcoholic consumption, as well as tumor-related features were collected. In addition, type of surgical intervention and relevant data, which were reported to be associated with complications of major head and neck procedures in the literature (such as peri-operative blood loss, concurrent neck dissection, and type of mandible resection) were also recorded. All PMMF were transferred to the head and neck region through a supraclavicular tunnel. The definition of recipient site infection was modified from Johnson et al. [12], which was purulent discharge either spontaneously or by incision and drainage from recipient site of PMMF with/without the presence of an oro-cutaneous fistula regardless of etiology within 30 days after operation. The definition of skin flap total necrosis was total loss of skin paddle, while partial loss of skin paddle was defined as skin flap partial necrosis. We used descriptive statistics for general data presentation. Comparisons of nominal or ordinal variables between subgroups were analyzed by Chi square test or Fisher’s exact test, whereas continuous variables were examined by Student’s t test. In addition, we used a receiver operating characteristic (ROC) curve to identify a proper cutoff point for the continuous variables at which to divide the patients into two groups. Furthermore, stepwise backward logistic regression was used to determine correlations between the presence of recipient site infection and the variables according to the results of univariate analysis. Variables with P value of less than 0.05 during
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From March 1994 to December 2012, a total of 535 patients with head and neck cancer receiving surgical excision with reconstruction of PMMF were identified in our institute. Thirty-one (5.8 %) patients had free tissue transfer or other loco-regional flap simultaneously during reconstruction. In addition, 26 (4.9 %) patients had incomplete chart records. Adequate data were obtained from chart records of 478 patients. The average age of the studied population was 51.7 (±10.0) years and the majority of them were males (n = 472, 98.7 %). Three hundred and forty-two patients (71.5 %) were in the late stage, whereas 136 patients (28.5 %) were in the early stage. Most of the recipient sites were located in the oral cavity (n = 367, 76.8 %) followed by hypopharynx (n = 61, 12.8 %), oropharynx (n = 28, 5.9 %) and neck region (n = 22, 4.6 %). The majority of patients had habits of smoking (n = 400, 83.7 %), alcohol consumption (n = 344, 72.0 %), and betel quid chewing (n = 369, 77.2 %). Eighty-one patients (16.9 %) had previous operation for head and neck cancer, while 101 patients (21.1 %) had prior radiation therapy to the head and neck region. In addition, 116 patients (24.3 %) had prior chemotherapy. The indication of PMMF was mainly for reconstruction after extirpation of head and neck cancer (n = 446, 93.3 %). Only 32 patients (6.7 %) received PMMF for salvage procedures. The reasons for salvage procedures were soft tissue defect after surgical site infection (n = 16, 50.0 %), failure of free tissue transfer (n = 6, 18.8 %), osteoradionecrosis (n = 5, 15.6 %), and coverage of exposed carotid artery (n = 5, 15.6 %). In terms of comorbidities, 42 patients (8.8 %) had diabetes mellitus and 65 patients (13.6 %) had hypertension. More than half of the PMMF were harvested from the left side (n = 241, 50.4 %). The average area of skin island was 55.3 cm2 (±34.0 cm2). In 105 PMMF (22.0 %), the lower margin of skin islands were over the sixth intercostal space; while in 245 (51.3 %) and 101 (21.1 %) patients, the lower margin was over the seventh and eighth intercostal space, respectively. The lower margin of PMMF skin island beyond the eighth intercostal space was noted in 27 patients (5.6 %). Most of the PMMF (n = 329, 68.8 %) were for reconstruction of mucosal defects, whereas 42 (8.8 %) of them were for skin defects. Bipedicled PMMF
Eur Arch Otorhinolaryngol Table 1 Descriptive and bivariate analyses of patients who underwent PMMF reconstruction based on the recipient site infection status Variables
Total no. of patients (% in column)
No. of patients (%)
P value
Infectious group (n = 183)
Non-infectious group (n = 295)
Age, mean ± SD (year)
52.0 ± 10.1
52.6 ± 10.0
0.643
Gender (male/female)
181/2
291/4
0.999
23.1 ± 4.0
23.1 ± 3.8
0.943 0.729
2
BMI, mean ± SD (Kg/M ) Smoking Yes
400 (83.7 %)
155 (38.8 %)
245 (61.3 %)
No
78 (16.3 %)
28 (35.9 %)
50 (64.1 %)
Yes
344 (72.0 %)
137 (39.8 %)
207 (60.2 %)
No
134 (28.0 %)
46 (34.3 %)
88 (65.7 %)
Yes
369 (77.2 %)
140 (37.9 %)
229 (62.1 %)
No
109 (22.8 %)
43 (39.4 %)
66 (60.6 %)
Stage I, II
136 (28.5 %)
42 (30.9 %)
94 (69.1 %)
Stage III, IV
342 (71.5 %)
141 (41.2 %)
201 (58.8 %)
Alcohol consumption
0.314
Betel quid chewing
0.863
Tumor stage
0.046
Prior operation Yes
0.381 81 (16.9 %)
35 (43.2 %)
46 (56.8 %)
397 (83.1 %)
148 (37.3 %)
249 (62.7 %)
Yes
116 (24.3 %)
54 (46.6 %)
62 (53.4 %)
No
362 (75.7 %)
129 (35.6 %)
233 (64.4 %)
Yes
101 (21.1 %)
52 (51.5 %)
49 (48.5 %)
No
377 (78.9 %)
131 (34.7 %)
246 (65.3 %)
Yes
42 (8.8 %)
24 (57.1 %)
18 (42.9 %)
No
436 (91.2 %)
159 (36.5 %)
277 (63.5 %)
Yes
65 (13.6 %)
26 (40.0 %)
39 (60.0 %)
No
413 (86.4 %)
157 (38.0 %)
256 (62.0 %)
Primary reconstruction
446 (93.3 %)
170 (38.1 %)
276 (61.9 %)
Salvage procedure
32 (6.7 %)
13 (40.6 %)
19 (59.4 %)
217 (45.4 %)
99 (45.6 %)
118 (54.4 %)
261 (54.6 %)
84 (32.2 %)
177 (67.8 %)
No Prior chemotherapy
0.046
Prior radiotherapy
0.003
Diabetes mellitus
0.014
Hypertension
0.866
Surgical indication
Preoperative albumin level (g/dL) \4.0 C4.0
0.925
0.004
Preoperative hemoglobulin level (g/dL)
0.002
\13.0
194 (40.6 %)
91 (46.9 %)
103 (53.1 %)
C13.0
284 (59.4 %)
92 (32.4 %)
192 (67.6 %)
Oral cavity
367 (76.8 %)
135 (36.8 %)
232 (63.2 %)
Oropharynx
28 (5.9 %)
15 (53.6 %)
13 (46.4 %)
Hypopharynx
61 (12.8 %)
25 (41.0 %)
36 (59.0 %)
Neck
22 (4.6 %)
8 (36.4 %)
14 (63.6 %)
Reconstructive site
0.342
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Eur Arch Otorhinolaryngol Table 1 continued Variables
Total no. of patients (% in column)
No. of patients (%)
P value
Infectious group (n = 183)
Non-infectious group (n = 295)
237 (49.6 %)
94 (39.7 %)
143 (60.3 %)
Left Lower margin of PMMF
241 (50.4 %)
89 (36.9 %)
152 (63.1 %)
Sixth intercostal space
105 (22.0 %)
19 (18.1 %)
86 (81.9 %)
Seventh intercostal space
245 (51.3 %)
100 (40.8 %)
145 (59.2 %)
Eighth intercostal space
101 (21.1 %)
42 (41.6 %)
59 (58.4 %)
Below eighth intercostal space
27 (5.6 %)
22 (81.5 %)
5 (18.5 %)
\50
266 (55.6 %)
80 (30.1 %)
186 (69.9 %)
C50
212 (44.4 %)
103 (48.6 %)
109 (51.4 %)
329 (68.8 %)
116 (35.3 %)
213 (64.7 %)
PMMF donor site Right
0.603
\0.001
PMMF area (cm2)
\0.001
Surface for reconstruction Mucosa only
0.045
Skin only
42 (8.8 %)
15 (35.7 %)
27 (64.3 %)
Both mucosa and skin
107 (22.4 %)
52 (48.6 %)
55 (51.4 %)
Mandibulectomy
0.003
No
143 (29.9 %)
62 (43.4 %)
81 (56.6 %)
Marginal Segmental
185 (38.7 %) 106 (22.2 %)
57 (30.8 %) 38 (35.8 %)
128 (69.2 %) 68 (64.2 %)
Hemi
44 (9.2 %)
26 (59.1 %)
18 (40.9 %) \0.001
Mandibular plate Yes
109 (22.8 %)
56 (51.4 %)
53 (48.6 %)
No
369 (77.2 %)
127 (34.4 %)
242 (65.6 %)
No
62 (13.0 %)
21 (33.9 %)
41 (66.1 %)
Unilateral
325 (68.0 %)
115 (35.4 %)
210 (64.6 %)
Bilateral
91 (19.0 %)
47 (51.6 %)
44 (48.4 %)
Yes
158 (33.1 %)
88 (55.7 %)
70 (44.3 %)
No
320 (66.9 %)
95 (29.7 %)
225 (70.3 %)
\600
279 (58.4 %)
93 (33.3 %)
186 (66.7 %)
C600
199 (41.6 %)
90 (45.2 %)
109 (54.8 %)
371 (77.6 %)
112 (30.2 %)
259 (69.8 %)
107 (22.4 %)
71 (66.4 %)
36 (33.6 %)
Concurrent neck dissection
0.014
\0.001
Concurrent tracheotomy
Operation duration (min)
Peri-operative blood loss (mL) \1,200 C1,200
0.012
\0.001
Blood transfusion
0.037
Yes
402 (84.1 %)
162 (40.3 %)
240 (59.7 %)
No
76 (15.9 %)
21 (27.6 %)
55 (72.4 %)
PMMF pectoralis major myocutaneous flap, SD standard deviation, BMI body mass index
Fisher’s exact test
was noted in 107 patients (22.4 %) for simultaneous reconstruction of mucosal and skin defects. Twenty-one patients (4.4 %) experienced total flap necrosis, whereas 111 patients
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(23.2 %) had various degrees of flap necrosis. One hundred and fifty-eight patients (33.1 %) underwent tracheotomy during operation. Simultaneous mandibulectomy was
Eur Arch Otorhinolaryngol Table 2 Relationship between lower margin of pectoralis major myocutaneous flap skin island and flap necrosis
Lower margin
Total no. of patients (% in column)
Flap necrosis No
Partial
Total
Sixth intercostal space
105 (22.0 %)
94 (89.5 %)
8 (7.6 %)
3 (2.9 %)
Seventh intercostal space
245 (51.3 %)
175 (71.4 %)
62 (25.3 %)
8 (3.3 %)
Eighth intercostal space
101 (21.1 %)
70 (69.3 %)
27 (26.7 %)
4 (4.0 %)
27 (5.6 %)
7 (25.9 %)
14 (51.9 %)
6 (22.2 %)
Below eighth intercostal space
performed in 335 patients (70.1 %) with marginal, segmental, and hemi-mandibulectomy in 185, 106, and 44 patients, respectively. Mandibular plate reconstruction was needed in 109 patients (22.8 %). Three hundred and twenty-five patients (68.0 %) had concurrent unilateral neck dissection, while 91 patients (19.0 %) had bilateral neck dissections. The average operation duration was 590 min (±154 min). The average peri-operative blood loss was 968 mL (±540 mL) and 402 patients (84.1 %) required blood transfusion during operation. Recipient site infection of PMMF was identified in 183 (38.3 %) of patients within 30 days after operation. Stratification of the patients according to the recipients’ site infection status revealed no significant statistical differences between the two groups in age, sex ratio, body mass index (BMI), smoking, alcohol consumption, site of reconstruction, prior operation, and history of hypertension. However, late-stage patients tended to have a higher infection rate than that of early-stage patients (41.2 versus 30.9 %, P = 0.046). Those with prior radiation and a history of diabetes mellitus also had a higher infection rate than that of patients without (51.5 versus 34.7 %, P = 0.003, 57.1 versus 36.5 %, P = 0.014, respectively). Higher recipient site infection rates were found in patients with prior chemotherapy, lower preoperative serum albumin and hemoglobulin level, larger PMMF area, mandibular plate for reconstruction, concurrent neck dissection, and tracheotomy. Furthermore, there were significant differences between infectious group and non-infectious group in operation duration (613 ± 156 versus 576 ± 152 min, P = 0.010), peri-operative blood loss (1,044 ± 625 versus 905 ± 487 min, P = 0.010), and blood transfusion. Detailed data are presented in Table 1. In terms of flap necrosis status, the percentage of partial or total flap necrosis increased as the lower margin of skin island got lower. The data are shown in Table 2. ROC curve was used to identify a proper cutoff point for the continuous variables at which to divide the cases into two groups for each factor (preoperative serum albumin level C4.0 and\4.0 g/dL, preoperative hemoglobulin level C13.0 and \13.0 g/dL, PMMF area C50 and \50 cm2, operation duration C600 and \600 min, peri-operative blood loss C1,200 and \1,200 mL). The curves were
drawn according to the sensitivity and specificity that the variables could discriminate the development of recipient site infection. The longitudinal axial represents ‘‘sensitivity’’, whereas the horizontal axial represents ‘‘1 - specificity’’ (Fig. 1). The area under ROC curves for preoperative albumin and hemoglobulin level were 0.605 and 0.595, respectively (all with P \ 0.001). The sensitivity and specificity of variables were calculated and the cutoff point was chosen when the sensitivity and specificity were both as high as possible (Table 3). Finally, a stepwise backward logistic regression model was applied to determine the factors associated with recipient site infection of PMMF. Table 4 shows that prior radiation [odds ratio (OR) 1.844, P = 0.028], history of diabetes mellitus (OR 2.139, P = 0.035), lower margin of PMMF beyond the eighth intercostal space (OR 18.15, P \ 0.001), concurrent reconstruction of mandibular plate (OR 1.991, P = 0.006), concurrent tracheotomy (OR 2.383, P \ 0.001), and perioperative blood transfusion (OR 1.937, P = 0.031) were independent factors associated with recipient site infection of PMMF.
Discussion Free flaps are now recognized as the preferred reconstructive option for head and neck surgery due to the improvements in microsurgical techniques. However, free flaps are not suitable for every patient in every circumstance and PMMF is still a valuable reconstructive method for head and neck cancer patients. To the best of our knowledge, the present study is the largest series to investigate the relationship between lower margin of skin island of PMMF and recipient site infection. We found that extension of Skin Island beyond the eighth intercostal space markedly increased the possibility of flap necrosis and eventually increased the risk of recipient site infection of PMMF. A previous study on cadavers found that the skin perforator vessels originating from the fourth, fifth, and sixth intercostal branches of the internal thoracic artery were essential for the survival of PMMF skin paddle [13]. During PMMF preparation, the main blood flow of the abovementioned vessels was interrupted and their blood
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Fig. 1 Receiver operator characteristic curves for cutoff analysis of preoperative serum albumin and hemoglobulin level, pectoralis major myocutaneous flap (PMMF) area, operation duration, and perioperative blood loss in patients with recipient site infection. The area
under the curve is 0.605 for preoperative serum albumin and 0.595 for preoperative hemoglobulin level (left), 0.629 for PMMF area, 0.569 for operative duration, and 0.573 for peri-operative blood loss (right)
Table 3 Statistical parameters associated with recipient site infection of pectoralis major myocutaneous flap calculated using different cutoff values
electrocautery in preparing the skin paddle [9], elevation of underlying anterior sheath of the rectus abdominis muscle in inferiorly extended skin island [13], inclusion of the muscular branch of the third intercostal perforating branch in skin paddle [14], and preservation of lateral thoracic artery without compromising pedicle length by dividing the pectoralis minor muscle [15]. With the increasing popularity of free tissue transfer for primary reconstruction, PMMF has acquired secondary status [16]. However, the majority of patients underwent PMMF as the primary reconstruction after head and neck cancer excision in the current study. The disparity might be explained by the different health environments of patients. In addition, plastic surgeons are not always available in our institute. Therefore, PMMF was the alternative option in the coverage of a large defect after tumor extirpation in the current study. Our study failed to demonstrate salvage procedures, smoking, reconstructive site, age, gender, albumin \4 g/ dL, prior chemotherapy, bipedicled flaps, area of PMMF, and concurrent neck dissection as independent risk factors of recipient site infection of PMMF. The recipient site infection of PMMF in the current study was 38.3 %, which was higher than that reported in most of the previous studies [2–4, 7–9]. A comprehensive comparison of our results with those of other studies in the literature is somewhat difficult due to diversity in the study designs, methods of outcome measurements, and various studied populations. However, we did find concurrent tracheotomy to be an independent risk factor for recipient site infection of PMMF. A previous study indicated that secretions accumulated around a tracheotomy site or tube postoperatively might increase the possibility of wound colonization by communication between the respiratory tract and the neck wound [17]. Irradiation of the head and neck may
Preoperative albumin level cutoff (g/dL)
3.8
3.9
4.0
4.1
4.2
Sensitivity (%)
68.1
60.0
53.6
45.1
38.0
Specificity (%)
47.0
55.1
65.0
72.9
78.1
12.0
12.5
13.0
13.5
14.0
76.6
70.8
65.1
55.6
46.1
35.5
43.2
49.7
59.0
66.7
30
40
50
60
70
Sensitivity (%)
82.0
71.0
56.3
38.8
29.5
Specificity (%)
28.8
47.5
63.1
79.3
83.4
500
550
600
650
700
Sensitivity (%)
79.0
62.4
50.3
34.8
24.9
Specificity (%)
28.2
41.8
61.9
73.5
84.7
1000
1100
1200
1300
1400
Sensitivity (%)
50.3
43.2
38.8
31.7
27.9
Specificity (%)
61.0
80.3
87.8
89.8
91.2
Preoperative hemoglobulin level cutoff (g/dL) Sensitivity (%) Specificity (%) PMMF area cutoff (cm2)
Operation duration cutoff (min)
Peri-operative blood loss cutoff (mL)
PMMF pectoralis major myocutaneous flap
supply was through open choke vessels from the pectoralis branch of the thoracoacromial artery. Below the seventh intercostal space, the vascular supply of the skin arises from the cutaneous branches of the superior epigastric artery. Therefore, skin island of PMMF beyond the seventh intercostal space would increase the risk of partial skin loss [13]. In the current study, the percentage of skin flap necrosis increased in proportion to how far downward the lower margin of the skin island extended. Previous studies also had similar results [8, 9]. Therefore, some modifications or suggestions were proposed by previous studies to increase the survival of PMMF, such as avoidance of
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Sixth intercostal spacea
105
1.000
Seventh intercostal space
245
3.467 \0.001
1.919
6.264
likelihood of postoperative wound infection [18]. Perioperative blood transfusion was reported to have an immunosuppressive effect that increased the possibility of postoperative wound infection. In addition, the need of blood transfusion or mandibular plate reconstruction also implied extensive tissue ablation and a large surgical defect [18]. Foreign body reaction might further render patients with mandibular plate reconstruction more prone to postoperative infection. A major strength of the present study was the use of a large population of head and neck cancer patients who underwent PMMF reconstruction in a single hospital (tertiary referral center) with meticulous statistical analyses. However, there were several limitations in our study. First, external validity of the findings is limited because this study was conducted at a single institution. Second, this study included various subsites of head and neck cancers, which may have different characteristics. Third, this was a retrospective study rather than a cohort study and thus it was difficult to clarify the causal relationships. Lastly, although the treatment guidelines are standardized at our institute, individual variations among surgeons inevitably exist.
Eighth intercostal space
101
3.201
0.001
1.635
6.266
Conclusions
Below eighth intercostal space
27
\0.001
5.708
0.513
0.720
1.931
0.006
1.215
3.260
Table 4 Factors associated with recipient site infection of PMMF based on logistic regression model Variables
No. of patients (N = 478)
Odds Ratio
P value
95 % Confidence interval Lower limit
Upper limit
Age (years) \50a
211
1.000
C50
267
1.677
377
1.000
Yes 101 Diabetes mellitus
1.844
0.553
0.744
1.793
0.028
1.068
3.183
0.035
1.055
4.337
Prior radiation Noa
Noa
436
1.000
Yes
42
2.139
\0.001
Lower margin of PMMF
PMMF area (cm2) \50a 266 C50
18.15
57.70
1.000
212
1.179
Noa
369
1.000
Yes
109
1.991
Mandibular plate
A certain portion of head and neck patients who underwent PMMF reconstruction after tumor excision experienced recipient site infection postoperatively. Skin island of PMMF beyond the eighth intercostal space markedly increased the possibility of recipient site infection after major head and neck cancer surgery. Recognition of relevant factors associated with infection may help surgeons to identify those at high risk and can enable better management of such cases.
Concurrent tracheotomy Noa
320
1.000
Yes
158
2.383 \0.001
1.477
3.844
1.061
3.536
Blood transfusion
a
Noa
76
1.000
Yes
402
1.937
0.031
Reference group
induce microvascular injury, fibrosis, and tissue necrosis. Radiation-related fibroblast dysfunction and defective collagen deposition may also cause poor wound healing leading to serious surgical site infection [17]. This is probably the reason why our study found prior radiation to be a risk factor of recipient site infection of PMMF. Diabetes mellitus is a systemic disease and is well known to cause microvasculopathy and immunosuppression, which influences the wound healing and increases the
Acknowledgments The authors thank the Biostatistics Task Force of Taichung Veterans General Hospital for their assistance with the statistical analysis. The study was partially supported by grants from Taichung Veterans General Hospital (TCVGH-1037004C), Taichung, Taiwan, Republic of China. No potential conflict of interest was involved in this research. Conflict of interest The authors have no potential conflicts of interest to report. Role of the Sponsors The Taichung Veterans General Hospital had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript.
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18.
revascularized free tissue transfer: complications, gastrostomy tube dependence, and hospitalization. Arch Otolaryngol Head Neck Surg 130:181–186 Jsselstein CB, Hovius SE, ten Have BL, Wijthoff SJ, Sonneveld GJ, Meeuwis CA et al (1996) Is the pectoralis myocutaneous flap in intraoral and oropharyngeal reconstruction outdated? Am J Surg 172:259–262 Johnson JT, Myers EN, Thearle PB, Sigler BA, Schramm VL Jr (1984) Antimicrobial prophylaxis for contaminated head and neck surgery. Laryngoscope 94:46–51 Rikimaru H, Kiyokawa K, Inoue Y, Tai Y (2005) Three-dimensional anatomical vascular distribution in the pectoralis major myocutaneous flap. Plast Reconstr Surg 115:1342–1352 (discussion 1353–1354) Rikimaru H, Kiyokawa K, Watanabe K, Koga N, Nishi Y, Sakamoto A (2009) New method of preparing a pectoralis major myocutaneous flap with a skin paddle that includes the third intercostal perforating branch of the internal thoracic artery. Plast Reconstr Surg 123:1220–1228 Po-Wing Yuen A (2006) Preservation of lateral thoracic artery to improve vascular supply of distal skin without compromising pedicle length in harvesting pectoralis major myocutaneous flap. J Plast Reconstr Aesthet Surg 59:1433–1435 Schneider DS, Wu V, Wax MK (2012) Indications for pedicled pectoralis major flap in a free tissue transfer practice. Head Neck 34:1106–1110 Lee DH, Kim SY, Nam SY, Choi SH, Choi JW, Roh JL (2011) Risk factors of surgical site infection in patients undergoing major oncological surgery for head and neck cancer. Oral Oncol 47:528–531 Liu SA, Wong YK, Poon CK, Wang CC, Wang CP, Tung KC (2007) Risk factors for wound infection after surgery in primary oral cavity cancer patients. Laryngoscope 117:166–171
HEAD AND NECK
Risk factors of recipient site infection in head and neck cancer patients undergoing pectoralis major myocutaneous flap reconstruction Chao-Hsien Wang • Yong-Kie Wong • Ching-Ping Wang • Chen-Chi Wang • Rong-San Jiang • Chih-Sheng Lai • Shih-An Liu
Received: 29 July 2014 / Accepted: 22 October 2014 Ó Springer-Verlag Berlin Heidelberg 2014
Abstract The aim of this study was to investigate the factors associated with infection at the recipient site of pectoralis major myocutaneous flap (PMMF) of head and neck cancer patients. We retrospectively reviewed head and neck cancer patients who underwent PMMF reconstruction and identified those with recipient site infection. Variables of patients with and without infection were compared and associated factors were investigated by logistic regression model. A total of 478 patients were included in the final analysis and 183 patients (38.3 %) developed recipient site infection. Lower margin of skin island, concurrent tracheotomy, diabetes mellitus, mandibular plate reconstruction, prior radiation, and perioperative blood transfusion were independent factors associated with recipient site infection of PMMF. Skin island of PMMF beyond the eighth intercostal space markedly increased the risk of recipient site infection after major head and neck cancer surgery. Recognition of
C.-H. Wang C.-P. Wang C.-C. Wang R.-S. Jiang S.-A. Liu (&) Department of Otolaryngology, Taichung Veterans General Hospital, No. 1650, Sect 4, Taiwan Boulevard, Taichung, Taiwan e-mail: [email protected] Y.-K. Wong Department of Oral and Maxillofacial Surgery, Taichung Veterans General Hospital, Taichung, Taiwan C.-S. Lai Department of Plastic and Reconstructive Surgery, Taichung Veterans General Hospital, Taichung, Taiwan S.-A. Liu Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
relevant factors associated with infection may help surgeons to identify those at risk. Keywords Head neck cancer Pectoralis major myocutaneous flap Surgical site infection Radiation Logistic regression model
Introduction The pectoralis major myocutaneous flap (PMMF), which gets its blood supply mainly from the thoracoacromial artery, was first introduced in 1979 by Ariyan [1]. PMMF is recognized as one of the most important techniques in the reconstruction of major head and neck cancer surgery due to its simple technical aspects, versatility, and proximity to the head and neck region [2]. Although the increased popularity of free flap reconstruction in complex soft tissue with/without bony defect has somewhat surpassed the PMMF, it is still a very valuable and reliable reconstructive method for defect after extirpation of head and neck cancer [3]. The complication rates of PMMF were reported to range from 13 to 43 % in the literature [3–8]. Complications consisted of infection, wound dehiscence, fistula formation, seroma, hematoma, and flap necrosis [7]. Factors associated with higher complication rates included salvage procedures, number of pack-years of cigarettes smoked, oral cavity reconstructions [2, 5], age over 70, female gender, albumin \4 g/dL [5], number of comorbidities [2, 5, 6], prior radiation therapy [3, 6, 9], prior chemotherapy, bipedicled flaps [6], extension of the skin flap over the rectus sheath [8], hypopharyngeal defect [9, 10], and concurrent anterior mandibular plate reconstruction [11]. However, fewer studies have investigated recipient site infection of
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PMMF and the relationship between lower margin of PMMF skin island and complications. Therefore, the aim of this study was to investigate the rate of recipient site infection after PMMF reconstruction in a large cohort of head and neck cancer patients. Furthermore, we determined the associated factors of recipient site infection after PMMF reconstruction by logistic regression analyses.
logistic regression analysis were excluded for further logistic regression model. Finally, the logistic regression model was adjusted for age. All statistical analyses were performed using SPSS for Windows, version 12.1 (SPSS, Chicago, IL, USA), and a P value \0.05 was regarded as statistically significant.
Results Materials and methods This study protocol was approved by the Institutional Review Board of Taichung Veterans General Hospital. We retrospectively reviewed over 2,000 chart records of head and neck cancer patients receiving surgical intervention in the studied hospital from March 1994 to December 2012. Those who underwent PMMF reconstruction were eligible for the current study. Those who had received other flap reconstruction simultaneously or had inadequate chart records were excluded. All patients were restaged according to the guidelines of the American Joint Committee on Cancer. Patients with stage I or II diseases were regarded as early stage, whereas those with stage III or IV were defined as late stage. Basic demographic data including age, gender, and personal habits such as smoking, alcoholic consumption, as well as tumor-related features were collected. In addition, type of surgical intervention and relevant data, which were reported to be associated with complications of major head and neck procedures in the literature (such as peri-operative blood loss, concurrent neck dissection, and type of mandible resection) were also recorded. All PMMF were transferred to the head and neck region through a supraclavicular tunnel. The definition of recipient site infection was modified from Johnson et al. [12], which was purulent discharge either spontaneously or by incision and drainage from recipient site of PMMF with/without the presence of an oro-cutaneous fistula regardless of etiology within 30 days after operation. The definition of skin flap total necrosis was total loss of skin paddle, while partial loss of skin paddle was defined as skin flap partial necrosis. We used descriptive statistics for general data presentation. Comparisons of nominal or ordinal variables between subgroups were analyzed by Chi square test or Fisher’s exact test, whereas continuous variables were examined by Student’s t test. In addition, we used a receiver operating characteristic (ROC) curve to identify a proper cutoff point for the continuous variables at which to divide the patients into two groups. Furthermore, stepwise backward logistic regression was used to determine correlations between the presence of recipient site infection and the variables according to the results of univariate analysis. Variables with P value of less than 0.05 during
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From March 1994 to December 2012, a total of 535 patients with head and neck cancer receiving surgical excision with reconstruction of PMMF were identified in our institute. Thirty-one (5.8 %) patients had free tissue transfer or other loco-regional flap simultaneously during reconstruction. In addition, 26 (4.9 %) patients had incomplete chart records. Adequate data were obtained from chart records of 478 patients. The average age of the studied population was 51.7 (±10.0) years and the majority of them were males (n = 472, 98.7 %). Three hundred and forty-two patients (71.5 %) were in the late stage, whereas 136 patients (28.5 %) were in the early stage. Most of the recipient sites were located in the oral cavity (n = 367, 76.8 %) followed by hypopharynx (n = 61, 12.8 %), oropharynx (n = 28, 5.9 %) and neck region (n = 22, 4.6 %). The majority of patients had habits of smoking (n = 400, 83.7 %), alcohol consumption (n = 344, 72.0 %), and betel quid chewing (n = 369, 77.2 %). Eighty-one patients (16.9 %) had previous operation for head and neck cancer, while 101 patients (21.1 %) had prior radiation therapy to the head and neck region. In addition, 116 patients (24.3 %) had prior chemotherapy. The indication of PMMF was mainly for reconstruction after extirpation of head and neck cancer (n = 446, 93.3 %). Only 32 patients (6.7 %) received PMMF for salvage procedures. The reasons for salvage procedures were soft tissue defect after surgical site infection (n = 16, 50.0 %), failure of free tissue transfer (n = 6, 18.8 %), osteoradionecrosis (n = 5, 15.6 %), and coverage of exposed carotid artery (n = 5, 15.6 %). In terms of comorbidities, 42 patients (8.8 %) had diabetes mellitus and 65 patients (13.6 %) had hypertension. More than half of the PMMF were harvested from the left side (n = 241, 50.4 %). The average area of skin island was 55.3 cm2 (±34.0 cm2). In 105 PMMF (22.0 %), the lower margin of skin islands were over the sixth intercostal space; while in 245 (51.3 %) and 101 (21.1 %) patients, the lower margin was over the seventh and eighth intercostal space, respectively. The lower margin of PMMF skin island beyond the eighth intercostal space was noted in 27 patients (5.6 %). Most of the PMMF (n = 329, 68.8 %) were for reconstruction of mucosal defects, whereas 42 (8.8 %) of them were for skin defects. Bipedicled PMMF
Eur Arch Otorhinolaryngol Table 1 Descriptive and bivariate analyses of patients who underwent PMMF reconstruction based on the recipient site infection status Variables
Total no. of patients (% in column)
No. of patients (%)
P value
Infectious group (n = 183)
Non-infectious group (n = 295)
Age, mean ± SD (year)
52.0 ± 10.1
52.6 ± 10.0
0.643
Gender (male/female)
181/2
291/4
0.999
23.1 ± 4.0
23.1 ± 3.8
0.943 0.729
2
BMI, mean ± SD (Kg/M ) Smoking Yes
400 (83.7 %)
155 (38.8 %)
245 (61.3 %)
No
78 (16.3 %)
28 (35.9 %)
50 (64.1 %)
Yes
344 (72.0 %)
137 (39.8 %)
207 (60.2 %)
No
134 (28.0 %)
46 (34.3 %)
88 (65.7 %)
Yes
369 (77.2 %)
140 (37.9 %)
229 (62.1 %)
No
109 (22.8 %)
43 (39.4 %)
66 (60.6 %)
Stage I, II
136 (28.5 %)
42 (30.9 %)
94 (69.1 %)
Stage III, IV
342 (71.5 %)
141 (41.2 %)
201 (58.8 %)
Alcohol consumption
0.314
Betel quid chewing
0.863
Tumor stage
0.046
Prior operation Yes
0.381 81 (16.9 %)
35 (43.2 %)
46 (56.8 %)
397 (83.1 %)
148 (37.3 %)
249 (62.7 %)
Yes
116 (24.3 %)
54 (46.6 %)
62 (53.4 %)
No
362 (75.7 %)
129 (35.6 %)
233 (64.4 %)
Yes
101 (21.1 %)
52 (51.5 %)
49 (48.5 %)
No
377 (78.9 %)
131 (34.7 %)
246 (65.3 %)
Yes
42 (8.8 %)
24 (57.1 %)
18 (42.9 %)
No
436 (91.2 %)
159 (36.5 %)
277 (63.5 %)
Yes
65 (13.6 %)
26 (40.0 %)
39 (60.0 %)
No
413 (86.4 %)
157 (38.0 %)
256 (62.0 %)
Primary reconstruction
446 (93.3 %)
170 (38.1 %)
276 (61.9 %)
Salvage procedure
32 (6.7 %)
13 (40.6 %)
19 (59.4 %)
217 (45.4 %)
99 (45.6 %)
118 (54.4 %)
261 (54.6 %)
84 (32.2 %)
177 (67.8 %)
No Prior chemotherapy
0.046
Prior radiotherapy
0.003
Diabetes mellitus
0.014
Hypertension
0.866
Surgical indication
Preoperative albumin level (g/dL) \4.0 C4.0
0.925
0.004
Preoperative hemoglobulin level (g/dL)
0.002
\13.0
194 (40.6 %)
91 (46.9 %)
103 (53.1 %)
C13.0
284 (59.4 %)
92 (32.4 %)
192 (67.6 %)
Oral cavity
367 (76.8 %)
135 (36.8 %)
232 (63.2 %)
Oropharynx
28 (5.9 %)
15 (53.6 %)
13 (46.4 %)
Hypopharynx
61 (12.8 %)
25 (41.0 %)
36 (59.0 %)
Neck
22 (4.6 %)
8 (36.4 %)
14 (63.6 %)
Reconstructive site
0.342
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Eur Arch Otorhinolaryngol Table 1 continued Variables
Total no. of patients (% in column)
No. of patients (%)
P value
Infectious group (n = 183)
Non-infectious group (n = 295)
237 (49.6 %)
94 (39.7 %)
143 (60.3 %)
Left Lower margin of PMMF
241 (50.4 %)
89 (36.9 %)
152 (63.1 %)
Sixth intercostal space
105 (22.0 %)
19 (18.1 %)
86 (81.9 %)
Seventh intercostal space
245 (51.3 %)
100 (40.8 %)
145 (59.2 %)
Eighth intercostal space
101 (21.1 %)
42 (41.6 %)
59 (58.4 %)
Below eighth intercostal space
27 (5.6 %)
22 (81.5 %)
5 (18.5 %)
\50
266 (55.6 %)
80 (30.1 %)
186 (69.9 %)
C50
212 (44.4 %)
103 (48.6 %)
109 (51.4 %)
329 (68.8 %)
116 (35.3 %)
213 (64.7 %)
PMMF donor site Right
0.603
\0.001
PMMF area (cm2)
\0.001
Surface for reconstruction Mucosa only
0.045
Skin only
42 (8.8 %)
15 (35.7 %)
27 (64.3 %)
Both mucosa and skin
107 (22.4 %)
52 (48.6 %)
55 (51.4 %)
Mandibulectomy
0.003
No
143 (29.9 %)
62 (43.4 %)
81 (56.6 %)
Marginal Segmental
185 (38.7 %) 106 (22.2 %)
57 (30.8 %) 38 (35.8 %)
128 (69.2 %) 68 (64.2 %)
Hemi
44 (9.2 %)
26 (59.1 %)
18 (40.9 %) \0.001
Mandibular plate Yes
109 (22.8 %)
56 (51.4 %)
53 (48.6 %)
No
369 (77.2 %)
127 (34.4 %)
242 (65.6 %)
No
62 (13.0 %)
21 (33.9 %)
41 (66.1 %)
Unilateral
325 (68.0 %)
115 (35.4 %)
210 (64.6 %)
Bilateral
91 (19.0 %)
47 (51.6 %)
44 (48.4 %)
Yes
158 (33.1 %)
88 (55.7 %)
70 (44.3 %)
No
320 (66.9 %)
95 (29.7 %)
225 (70.3 %)
\600
279 (58.4 %)
93 (33.3 %)
186 (66.7 %)
C600
199 (41.6 %)
90 (45.2 %)
109 (54.8 %)
371 (77.6 %)
112 (30.2 %)
259 (69.8 %)
107 (22.4 %)
71 (66.4 %)
36 (33.6 %)
Concurrent neck dissection
0.014
\0.001
Concurrent tracheotomy
Operation duration (min)
Peri-operative blood loss (mL) \1,200 C1,200
0.012
\0.001
Blood transfusion
0.037
Yes
402 (84.1 %)
162 (40.3 %)
240 (59.7 %)
No
76 (15.9 %)
21 (27.6 %)
55 (72.4 %)
PMMF pectoralis major myocutaneous flap, SD standard deviation, BMI body mass index
Fisher’s exact test
was noted in 107 patients (22.4 %) for simultaneous reconstruction of mucosal and skin defects. Twenty-one patients (4.4 %) experienced total flap necrosis, whereas 111 patients
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(23.2 %) had various degrees of flap necrosis. One hundred and fifty-eight patients (33.1 %) underwent tracheotomy during operation. Simultaneous mandibulectomy was
Eur Arch Otorhinolaryngol Table 2 Relationship between lower margin of pectoralis major myocutaneous flap skin island and flap necrosis
Lower margin
Total no. of patients (% in column)
Flap necrosis No
Partial
Total
Sixth intercostal space
105 (22.0 %)
94 (89.5 %)
8 (7.6 %)
3 (2.9 %)
Seventh intercostal space
245 (51.3 %)
175 (71.4 %)
62 (25.3 %)
8 (3.3 %)
Eighth intercostal space
101 (21.1 %)
70 (69.3 %)
27 (26.7 %)
4 (4.0 %)
27 (5.6 %)
7 (25.9 %)
14 (51.9 %)
6 (22.2 %)
Below eighth intercostal space
performed in 335 patients (70.1 %) with marginal, segmental, and hemi-mandibulectomy in 185, 106, and 44 patients, respectively. Mandibular plate reconstruction was needed in 109 patients (22.8 %). Three hundred and twenty-five patients (68.0 %) had concurrent unilateral neck dissection, while 91 patients (19.0 %) had bilateral neck dissections. The average operation duration was 590 min (±154 min). The average peri-operative blood loss was 968 mL (±540 mL) and 402 patients (84.1 %) required blood transfusion during operation. Recipient site infection of PMMF was identified in 183 (38.3 %) of patients within 30 days after operation. Stratification of the patients according to the recipients’ site infection status revealed no significant statistical differences between the two groups in age, sex ratio, body mass index (BMI), smoking, alcohol consumption, site of reconstruction, prior operation, and history of hypertension. However, late-stage patients tended to have a higher infection rate than that of early-stage patients (41.2 versus 30.9 %, P = 0.046). Those with prior radiation and a history of diabetes mellitus also had a higher infection rate than that of patients without (51.5 versus 34.7 %, P = 0.003, 57.1 versus 36.5 %, P = 0.014, respectively). Higher recipient site infection rates were found in patients with prior chemotherapy, lower preoperative serum albumin and hemoglobulin level, larger PMMF area, mandibular plate for reconstruction, concurrent neck dissection, and tracheotomy. Furthermore, there were significant differences between infectious group and non-infectious group in operation duration (613 ± 156 versus 576 ± 152 min, P = 0.010), peri-operative blood loss (1,044 ± 625 versus 905 ± 487 min, P = 0.010), and blood transfusion. Detailed data are presented in Table 1. In terms of flap necrosis status, the percentage of partial or total flap necrosis increased as the lower margin of skin island got lower. The data are shown in Table 2. ROC curve was used to identify a proper cutoff point for the continuous variables at which to divide the cases into two groups for each factor (preoperative serum albumin level C4.0 and\4.0 g/dL, preoperative hemoglobulin level C13.0 and \13.0 g/dL, PMMF area C50 and \50 cm2, operation duration C600 and \600 min, peri-operative blood loss C1,200 and \1,200 mL). The curves were
drawn according to the sensitivity and specificity that the variables could discriminate the development of recipient site infection. The longitudinal axial represents ‘‘sensitivity’’, whereas the horizontal axial represents ‘‘1 - specificity’’ (Fig. 1). The area under ROC curves for preoperative albumin and hemoglobulin level were 0.605 and 0.595, respectively (all with P \ 0.001). The sensitivity and specificity of variables were calculated and the cutoff point was chosen when the sensitivity and specificity were both as high as possible (Table 3). Finally, a stepwise backward logistic regression model was applied to determine the factors associated with recipient site infection of PMMF. Table 4 shows that prior radiation [odds ratio (OR) 1.844, P = 0.028], history of diabetes mellitus (OR 2.139, P = 0.035), lower margin of PMMF beyond the eighth intercostal space (OR 18.15, P \ 0.001), concurrent reconstruction of mandibular plate (OR 1.991, P = 0.006), concurrent tracheotomy (OR 2.383, P \ 0.001), and perioperative blood transfusion (OR 1.937, P = 0.031) were independent factors associated with recipient site infection of PMMF.
Discussion Free flaps are now recognized as the preferred reconstructive option for head and neck surgery due to the improvements in microsurgical techniques. However, free flaps are not suitable for every patient in every circumstance and PMMF is still a valuable reconstructive method for head and neck cancer patients. To the best of our knowledge, the present study is the largest series to investigate the relationship between lower margin of skin island of PMMF and recipient site infection. We found that extension of Skin Island beyond the eighth intercostal space markedly increased the possibility of flap necrosis and eventually increased the risk of recipient site infection of PMMF. A previous study on cadavers found that the skin perforator vessels originating from the fourth, fifth, and sixth intercostal branches of the internal thoracic artery were essential for the survival of PMMF skin paddle [13]. During PMMF preparation, the main blood flow of the abovementioned vessels was interrupted and their blood
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Fig. 1 Receiver operator characteristic curves for cutoff analysis of preoperative serum albumin and hemoglobulin level, pectoralis major myocutaneous flap (PMMF) area, operation duration, and perioperative blood loss in patients with recipient site infection. The area
under the curve is 0.605 for preoperative serum albumin and 0.595 for preoperative hemoglobulin level (left), 0.629 for PMMF area, 0.569 for operative duration, and 0.573 for peri-operative blood loss (right)
Table 3 Statistical parameters associated with recipient site infection of pectoralis major myocutaneous flap calculated using different cutoff values
electrocautery in preparing the skin paddle [9], elevation of underlying anterior sheath of the rectus abdominis muscle in inferiorly extended skin island [13], inclusion of the muscular branch of the third intercostal perforating branch in skin paddle [14], and preservation of lateral thoracic artery without compromising pedicle length by dividing the pectoralis minor muscle [15]. With the increasing popularity of free tissue transfer for primary reconstruction, PMMF has acquired secondary status [16]. However, the majority of patients underwent PMMF as the primary reconstruction after head and neck cancer excision in the current study. The disparity might be explained by the different health environments of patients. In addition, plastic surgeons are not always available in our institute. Therefore, PMMF was the alternative option in the coverage of a large defect after tumor extirpation in the current study. Our study failed to demonstrate salvage procedures, smoking, reconstructive site, age, gender, albumin \4 g/ dL, prior chemotherapy, bipedicled flaps, area of PMMF, and concurrent neck dissection as independent risk factors of recipient site infection of PMMF. The recipient site infection of PMMF in the current study was 38.3 %, which was higher than that reported in most of the previous studies [2–4, 7–9]. A comprehensive comparison of our results with those of other studies in the literature is somewhat difficult due to diversity in the study designs, methods of outcome measurements, and various studied populations. However, we did find concurrent tracheotomy to be an independent risk factor for recipient site infection of PMMF. A previous study indicated that secretions accumulated around a tracheotomy site or tube postoperatively might increase the possibility of wound colonization by communication between the respiratory tract and the neck wound [17]. Irradiation of the head and neck may
Preoperative albumin level cutoff (g/dL)
3.8
3.9
4.0
4.1
4.2
Sensitivity (%)
68.1
60.0
53.6
45.1
38.0
Specificity (%)
47.0
55.1
65.0
72.9
78.1
12.0
12.5
13.0
13.5
14.0
76.6
70.8
65.1
55.6
46.1
35.5
43.2
49.7
59.0
66.7
30
40
50
60
70
Sensitivity (%)
82.0
71.0
56.3
38.8
29.5
Specificity (%)
28.8
47.5
63.1
79.3
83.4
500
550
600
650
700
Sensitivity (%)
79.0
62.4
50.3
34.8
24.9
Specificity (%)
28.2
41.8
61.9
73.5
84.7
1000
1100
1200
1300
1400
Sensitivity (%)
50.3
43.2
38.8
31.7
27.9
Specificity (%)
61.0
80.3
87.8
89.8
91.2
Preoperative hemoglobulin level cutoff (g/dL) Sensitivity (%) Specificity (%) PMMF area cutoff (cm2)
Operation duration cutoff (min)
Peri-operative blood loss cutoff (mL)
PMMF pectoralis major myocutaneous flap
supply was through open choke vessels from the pectoralis branch of the thoracoacromial artery. Below the seventh intercostal space, the vascular supply of the skin arises from the cutaneous branches of the superior epigastric artery. Therefore, skin island of PMMF beyond the seventh intercostal space would increase the risk of partial skin loss [13]. In the current study, the percentage of skin flap necrosis increased in proportion to how far downward the lower margin of the skin island extended. Previous studies also had similar results [8, 9]. Therefore, some modifications or suggestions were proposed by previous studies to increase the survival of PMMF, such as avoidance of
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Sixth intercostal spacea
105
1.000
Seventh intercostal space
245
3.467 \0.001
1.919
6.264
likelihood of postoperative wound infection [18]. Perioperative blood transfusion was reported to have an immunosuppressive effect that increased the possibility of postoperative wound infection. In addition, the need of blood transfusion or mandibular plate reconstruction also implied extensive tissue ablation and a large surgical defect [18]. Foreign body reaction might further render patients with mandibular plate reconstruction more prone to postoperative infection. A major strength of the present study was the use of a large population of head and neck cancer patients who underwent PMMF reconstruction in a single hospital (tertiary referral center) with meticulous statistical analyses. However, there were several limitations in our study. First, external validity of the findings is limited because this study was conducted at a single institution. Second, this study included various subsites of head and neck cancers, which may have different characteristics. Third, this was a retrospective study rather than a cohort study and thus it was difficult to clarify the causal relationships. Lastly, although the treatment guidelines are standardized at our institute, individual variations among surgeons inevitably exist.
Eighth intercostal space
101
3.201
0.001
1.635
6.266
Conclusions
Below eighth intercostal space
27
\0.001
5.708
0.513
0.720
1.931
0.006
1.215
3.260
Table 4 Factors associated with recipient site infection of PMMF based on logistic regression model Variables
No. of patients (N = 478)
Odds Ratio
P value
95 % Confidence interval Lower limit
Upper limit
Age (years) \50a
211
1.000
C50
267
1.677
377
1.000
Yes 101 Diabetes mellitus
1.844
0.553
0.744
1.793
0.028
1.068
3.183
0.035
1.055
4.337
Prior radiation Noa
Noa
436
1.000
Yes
42
2.139
\0.001
Lower margin of PMMF
PMMF area (cm2) \50a 266 C50
18.15
57.70
1.000
212
1.179
Noa
369
1.000
Yes
109
1.991
Mandibular plate
A certain portion of head and neck patients who underwent PMMF reconstruction after tumor excision experienced recipient site infection postoperatively. Skin island of PMMF beyond the eighth intercostal space markedly increased the possibility of recipient site infection after major head and neck cancer surgery. Recognition of relevant factors associated with infection may help surgeons to identify those at high risk and can enable better management of such cases.
Concurrent tracheotomy Noa
320
1.000
Yes
158
2.383 \0.001
1.477
3.844
1.061
3.536
Blood transfusion
a
Noa
76
1.000
Yes
402
1.937
0.031
Reference group
induce microvascular injury, fibrosis, and tissue necrosis. Radiation-related fibroblast dysfunction and defective collagen deposition may also cause poor wound healing leading to serious surgical site infection [17]. This is probably the reason why our study found prior radiation to be a risk factor of recipient site infection of PMMF. Diabetes mellitus is a systemic disease and is well known to cause microvasculopathy and immunosuppression, which influences the wound healing and increases the
Acknowledgments The authors thank the Biostatistics Task Force of Taichung Veterans General Hospital for their assistance with the statistical analysis. The study was partially supported by grants from Taichung Veterans General Hospital (TCVGH-1037004C), Taichung, Taiwan, Republic of China. No potential conflict of interest was involved in this research. Conflict of interest The authors have no potential conflicts of interest to report. Role of the Sponsors The Taichung Veterans General Hospital had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript.
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