Introduction

Oral squamous cell carcinoma (OSCC) is a common form of head and neck cancer [1]. It preferentially affects males, with a mean age of diagnosis in the fifth or sixth decades. Women and young adults are increasingly affected by OSCC [2]. The principal aetiology of this cancer is tobacco use, with alcohol as co-responsible factor [3]. Whenever possible, surgical removal with margins, in association with homo or bilateral cervical node resections, is the standard treatments [4]. Surgical resection and reconstruction can lead to functional and aesthetic disabilities, particularly with T3 and T4 tumours [5]. As it is considered to be a reliable technique, free flap surgery is often performed for reconstruction in head and neck cancers [6].

Patients suffering from OSCC have many comorbidities stemming from tobacco and alcohol dependence. An associated artery disease, high blood pressure, diabetes and malnutrition can lead to medical and surgical complications in the perioperative period. Oral feeding is suspended for a number of days in favour of gastrostomy or a feeding tube. Furthermore, although there is not a consensus regarding its use, a tracheostomy is often performed, and this can interfere with the recovery of oral feeding [7]. All of these factors can influence the postoperative morbi-mortality and free flap failure after tumour resection [8,9,10,11]. Moreover, practices vary considerably between teams and countries in terms of the peri- and postoperative care, such as nutrition and ventilation support.

The aim of this study was to identify the factors responsible for free flap failure, the surgical complications, and the non-oral feeding period in patients treated for an OSCC.

Materials and methods

Study design

This multicentric retrospective study involved five hospital centres in France and its overseas territories (the maxillofacial surgery (MFS) departments of Nantes and Lille, and the otorhinolaryngology (ENT) departments of Nantes, Lille, and Saint-Denis in Reunion) between 2010 and 2016. All of these centres are accredited and have the capacity to perform cancer surgery and microvascular reconstruction in keeping with head and neck cancer guidelines. The inclusion criteria were a first newly diagnosed and histologically defined OSCC, treated by radical resection with immediate free flap reconstruction. The exclusion criteria were other oral tumour entities (e.g. an adenocarcinoma, ameloblastoma), a medical history of previously treated OSCC, and head and neck radiotherapy. Patients for whom the relevant medical data was largely lacking were also excluded from the study.

This non-interventional study was approved by the ethics committee of the Nantes University Hospital, according to the Articles L. 1121-1 paragraph 1 and R 1121-2, paragraph 1 of the French Public Health Code.

Data collection

Two different investigators reviewed all of the medical files and they collected the data regarding the hospital stays. Thus, the complete examination and nursing records, the operative indications and procedures, the histopathological reports, and the medical-surgery-anaesthesiology records were compiled.

The data were divided into four groups for specific analyses:

  • The first group comprised the patient characteristics and their medical history: age, gender, high blood pressure controlled by medications, artery disease (including leg arteriopathy, carotid stenosis, and coronary heart disease CHD), and type 1 or type 2 diabetes. The body mass index (BMI) was calculated and the extent of tobacco and alcohol consumption was assessed. The physical status score from the American Society of Anaesthesiologists (ASA) was collected systematically. The patients were classified by the anaesthesiologist according to their comorbidities and their age, in order to predict the potential medical perioperative risk [12].

  • The second group comprised the tumour-related features: the TNM classification of the tumour, tumour grading (WHO) from I to IV (grade I (T1 N0), grade II (T2 N0), grade III (T1-2 N1; T3 N01), grade IV (T1-2-3-4 N> 2; T4 N0-1)) and the specific location of the disease (i.e. the mandible, mouth floor, palate, cheek, lip, tongue or intermaxillary commissure (IMC)).

  • The third group comprised the surgical procedure: the type of free flap reconstruction (i.e. a forearm fasciocutaneous flap, fibular flap, anterolateral thigh flap, scapular flap, lateral arm septocutaneous flap, dorsi flap, or lateral arm osteoseptocutaneous flap), the duration of the surgery (in hours), the use of a blood transfusion, tracheostomy, and the tracheostomy period (in days).

  • The fourth group comprised the data regarding the postoperative recovery: the duration of the hospital stay, free flap vitality at the end of stay, oral feeding at the end of the stay, the duration of non-oral feeding, and any deaths that occurred during the hospital stay. All of the postoperative complications were compiled and separated into medical and surgical complications, and each was categorised as being either a minor or a major complication. The major medical complications included life-threatening problems, whereas the major surgical complications threatened with the vitality of the free flap and required a second surgical procedure. The main causes were necrosis, orocutaneous fistula, bleeding, infection, and free flap ischemia.

Statistical analysis

The data were analysed using SAS® version 9.4 software (SAS Institute, Brie-Comte-Robert, France). The association of one of the studied criteria with potential risk factors was assessed. Factors exhibiting a significant association in univariate logistic regression analysis (p value < 0.20) were included in multivariate logistic regression models. We used a “bottom-up” method to define the final model. A p value < 0.05 was considered to be statistically significant.

Results

General results

Two hundred fifteen patients were included in the study according to the inclusion and exclusion criteria. Of these, 170 (79.1%) were males and 45 (20.9%) were females. The mean age of the patients was 58.6 years (ranging from 25 to 85). Ninety-seven patients (45.1%) were treated at the Nantes MFS unit, 42 (19.5%) at the Lille ENT unit, 31 (14.4%) at the Lille MFS unit, 25 (11.6%) at the Nantes ENT unit, and 20 (9.4%) at the Saint-Denis (Reunion) ENT unit.

Patient characteristics and medical histories (group 1)

Analysis of the patient medical files revealed that the majority of them had a tobacco dependence (66.5%), whereas close to half of the population (56.3%) had an alcohol dependence. The mean median BMI was normal as it was between 18 and 25. The proportion of patients with high blood pressure was 35.8%, artery disease was present in 19% of the patients, and 13% had diabetes. The ASA score was between 1 and 3, and none of the patients had a score between 4 and 6.

The patient characteristics are presented in Table 1.

Table 1 Patient characteristics and medical histories
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Tumour-related features (group 2)

Most of tumours occurred in the mouth floor, accounting for 55.3% (119) of the patients; whereas the tongue, the mandible, the inner side of the cheek, the IMC and the palate were involved in 15.8%, 13%, 6.5%, 6%, and 3.3% of the cases, respectively.

Most of the patients had grade IV disease (72.5%) and the majority of the tumours were T3 (22.8%) and T4 (58.2%) in size (according to the TNM classification). The node status was negative in nearly half of the cases (45.4%). The characteristics for all of the tumours are presented in Table 2.

Table 2 Tumour-related features; n, number of patients
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T tumour size; N, regional lymph nodes involved; M distant metastasis

Free flap surgical reconstruction and perioperative parameters (group 3)

A substantial proportion of the patients were reconstructed with a forearm fasciocutaneous flap (39.5%) or a fibular osseous free flap (30.8%). Other reconstructions included osseous and non-osseous lateral arm flaps (15.3%), musculocutaneous dorsi flaps (12.6%) and anterolateral thigh and scapular osseous flaps (1.8%).

The mean duration of the surgery was 7.7 h ± 2.08 h. A perioperative blood transfusion was provided to 163 patients (76.5%). A tracheostomy was performed on 143 patients (66.5%). Antibiotics were administered to 198 patients (92.1%).

Postoperative recovery and complications (group 4)

The hospital stay lasted 16.9 days ±9.76 days. The tracheostomy, when performed, was maintained for 12.8 days ±23.67 days. Non-oral feeding lasted 17.6 days ±28 days. At the end of the hospital stay, 71.6% of patients were fed orally, whereas 37 (17.6%) and 19 (9%) patients were fed by a feeding tube or a gastrostomy, respectively. The records indicate that 5 deaths (2.3%) occurred, 4 patients died from cardiorespiratory arrest and one died due to adult respiratory distress syndrome (ARDS). The free flap failure rate was 5.6%, occurring in 12 patients.

A postoperative complication occurred in 101 patients (41%) and was classified as a minor medical complication (46%), a major medical complication (10.2%), a minor surgical complication (24.6%), or a major surgical complication (22.3%). The most common minor medical complications were confusion due mostly to alcohol withdrawal, pneumonia, anaemia, and neurological or cardiac issues; the treatments comprised medical monitoring, blood transfusion, and the administration of medications. The most common major medical complications were bleeding, tracheostomy related accidents, and cardiac arrest; the treatments remained medical, with no surgical procedure being undertaken. The most common minor surgical complications were infection, bleeding, scars, partial necrosis, and orocutaneous fistula; the main treatments were medical control, local care, and occasionally the use of a hyperbaric chamber. The main surgical complications were orocutaneous fistula, full necrosis, infection, scars, and bleeding; all of these complications required a surgical treatment under general anaesthesia. When a patient presented with two types of complications, only the most severe one was taken into account. All of the complications were treated as independent variables and could be considered jointly in the multivariate analysis.

Seven factors were found to be associated with a free flap failure in the univariate logistic regression analysis (Table 3). The factor “hospital stay” was voluntarily removed from the multivariate analysis as it was closely linked to “non-oral feeding period,” “tracheostomy period” and “duration of surgery”. In the multivariate logistic regression model, the minor surgical complications were shown to increase the free flap failure rate (OR 3.32; 95% CI 1.02 – 10.78; p = 0.0459).

Table 3 Univariate logistic regression for the analysis of free flap failure; OR, odds ratio; 95% CI, 95% confidence interval
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A major surgical complication occurred in 48 patients (22.3%). Factors linked to major surgical complications were then analysed according to a univariate and multivariate logistic regression (Table 4). A protective effect of a medical history of high blood pressure was found in regard to the occurrence of a major surgical complication (OR 0.43, p = 0.038). Whereas minor surgical complications and the use of tracheostomy were found to predispose to a major surgical complication in our patients (OR 2.89, p = 0.004 and OR 5.76, p = 0.002, respectively).

Table 4 Multivariate logistic regression for the analysis of the major surgical complications; OR, odds ratio; 95% CI, 95% confidence interval
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At the end of the hospital stay, 28.4% of the patients were unable to eat normally and were fed by a feeding tube or a gastrostomy. The minor and major surgical complications, as well as the tracheostomy were found to be correlated with the failure of oral feeding (Table 5).

Table 5 Multivariate regression logistic model for the analysis of the oral feeding; OR, odds ratio; 95% CI, 95% confidence interval
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A statistical analysis was performed to identify the factors that could increase the need for a tracheostomy. The occurrence of a major surgical complication, a tumour of the mouth floor, and all free flaps except the forearm free flaps were found to increase the risk of a tracheostomy (Table 6).

Table 6 Multivariate regression logistic model for the tracheostomy indication; OR, odds ratio; 95% CI, 95% confidence interval
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Discussion

Microvascular reconstruction is considered to be a reliable technique for head and neck surgery [13, 14], as underscored by the increase in the success rate from 80 to 95% over the past 20 years. Our study aimed to establish the nature of the comorbidities in patients exhibiting an OSCC treated by surgical resection and free flap reconstruction, and to identify the risk factors associated with failure and perioperative complications. This could help refine and standardise the medical and the surgical practices for OSCC patients. Due to the risk of vessel stenosis, surgical complications, and free flap failures after head and neck radiotherapy [15, 16], patients with a medical history of radiotherapy were not included in this study.

We report a 94.4% success rate for the free flap reconstruction in the 215 patients who underwent treatment. Furthermore, the overall rate of complications was 47%, and the specific rate of major surgical complications was 22.3%. These results are in accordance with the data in the literature; although the tumour locations tended to be different, primarily affecting the oropharynx, the neck and the skin (Table 7). As highlighted by Dassonville et al., the main risk factor for free flap failure in our study was the occurrence of a surgical complication, such as an infection, postoperative bleeding, scars, partial necrosis, and orocutaneous fistula [20].

Table 7 Summary of the results found in the literature regarding the success rate for free flaps, the rate of surgical complications, and the death rate; *r, retrospective; p, prospective
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Tracheostomy was found to increase the incidence of major surgical complications and to delay oral feeding in the postoperative period. It was indicated in situations with a high risk of postoperative cervical oedema or in case of respiratory distress, with no consensus on its execution. To avoid a tracheostomy, Coyle et al. have suggested a postoperative protocol including 12 h of intubation in an intensive care unit (ICU), 8 mg of intravenous dexamethasone over a 72 h period, tube removal on the next day, and a return to the conventional medical unit. This protocol enhances the postoperative recovery and decreases the duration of the hospital stay [23, 24]. Based on the tumour location, the performance of a mandibulectomy, or bilateral cervical nodes dissection with reconstruction, the score proposed by Cameron et al. [25] helps predict the use of a tracheostomy. Furthermore, oral feeding resumes sooner when patients do not undergo a tracheostomy [7]. Forearm free flaps appeared to be associated less with a tracheostomy; these flaps are thinner, their harvesting is easier and shorter, and cervical oedema is hence rare [26]. On the other hand, osseous free flaps are more difficult to harvest and involve a longer surgery time, even when the surgeon is experienced in this regard [27, 28].

The surgical complications as well as the tracheostomy significantly increased the duration of the non-oral feeding period. A recent study has shown that early oral feeding does not increase the risk of orocutaneous fistula and it does not compromise the vitality of the free flap, with a shortened hospital stay as a result [29]. However, the question of whether to perform a preoperative gastrostomy remains. The present study did not indicate whether gastrostomy is preferable to a feeding tube.

In our study, high blood pressure that is being controlled by medication appeared to be a protective factor in regard to major surgical complications. To our knowledge, this factor has not been previously reported in the literature. Age was not a statistically significant factor for free flap failure, major surgical complications or the duration of the non-oral feeding period. These findings are in keeping with the results found in others studies [30,30,31,33]. Nevertheless, age is responsible for medical complications such as pulmonary or cardiac issues [18, 34], and a preoperative evaluation of comorbidities should be systematically undertaken, particularly with geriatric populations [35]. Many studies have identified diabetes as a risk factor for free flap failure, with a risk ratio in the literature that ranges from 2.3 to 5 [36,36,37,39]. Although 13% of the patients in our study were diabetics, we did not find a statistical correlation between diabetes and free flap failure. Similarly, the BMI and major surgical complications were not significant factors for free flap failure in our study. According to the literature, an extremely low BMI can lead to an increased risk of free flap complications [33]. New “nutritional practices” include a blood nutritional analysis (albuminemy, pre-albuminemy, phosphoremy) as well as food supply with a gastrostomy or a feeding tube during the preoperative period. The ASA score was not a predictive factor of free flap failure, major surgical complications, or non-oral feeding at the end of the hospital stay. Although the literature indicates that the ASA score is linked to major medical and surgical complications [11, 18], we did not find evidence for such a link in our series. Similarly, the duration of the surgery and a perioperative blood transfusion did not correlate with free flap failures or major surgical complications. It has been reported that surgeries lasting longer than 10 h are more subject to complications [15, 40].

The main limitation of our study is the retrospective nature of the data collection. To standardise the data collection method between the various centres, complications could have been selected according to the Clavien-Dindo-Strasberg classification [23]. This reliable classification method standardises data collection for investigators and it classifies postoperative complications. It is, however, not specific for head and neck surgery [24]. To increase the number of patients and thus the number of events (e.g. free flap failures and complications), our study was multicentric. Also, the practices and specialisations, in terms of perioperative and postoperative medical care, differed considerably between the centres participating in our study.

A study by Kruse et al. in 2010 led to recommendations based on the ASA score to decrease the risk of free flap complications [41]. These recommendations comprise postoperative respiratory physiotherapy, three doses of antibiotics, an anti-coagulant treatment for special indications (e.g. small vessels, lack of congruence between vessels, poor quality of vessels and vessel interposition), hourly monitoring of the free flap viability during the first day and then every 4 h over the next 2 days. It is preferably that monitoring of the free flap is done in a surveillance unit, so as to detect and treat any complications as soon as possible [42]. Various instrumental techniques have been developed for flap monitoring [43] (e.g. implantable Doppler system, colour duplex sonography, near-infrared spectroscopy, microdialysis, laser Doppler flowmetry), although none of them are used routinely.

Conclusion

Free flap reconstruction is a safe and reliable technique for head and neck cancer reconstruction. The occurrence of a minor surgical complication increases the risk of free flap failure. Tracheostomy increases the risk of major surgical complications and it increases the duration of the non-oral feeding period. This study also highlights the protective effect of controlled high blood pressure in regard to the occurrence of a major surgical complication after OSCC removal and reconstruction.