Concurrent chemoradiation therapy (CCRT) or organ preserving surgery with adjuvant treatment have been frequently used as an initial treatment in head and neck cancer [1,2], because of better functional outcome and a lower rate of acute complications than radical surgery [3]. However, with the increase of CCRT or organ preserving surgery, salvage surgery after failure of initial treatment is increasing and surgery is becoming more important for the treatment of recurrent or residual cancer [4]. Wide excision to achieve clear margins is important not only in primary but also in salvage surgery, and free flap surgery is the gold standard in the reconstruction of large surgical defects. Although the overall success rate of free flaps in the head and neck is known to be high [5-9], microvascular anastomosis in a previously treated neck will be technically more difficult to accomplish than normal condition but increasingly required for recurrent or residual cancer. When the flap’s survival is uncertain, rapid re-exploration is important. The overall unplanned reoperation rates after free flap surgery are known to range from 18.0% to 20.0% [10-14] and there are cases where free flaps are rescued through re-exploration, but there are cases where the rescue fails and the flaps are finally lost. The overall unplanned reoperation rates after free flap surgery are known to range from 18.0% to 20.0% [10-14], but there is a lack of accurate analysis of the risk of early complications, such as hemorrhage or venous congestion that necessitate immediate re-exploration, when microvascular anastomosis is performed in the neck where previous treatments such as radiation therapy (RT) or surgery have been performed. Given that unplanned reoperation for flap salvage is a burden to patients and surgeons and result in a prolonged hospital stay and increased health care costs, the identification of risk factors of flap failure or re-exploration is important for treatment. Previous studies have shown that reoperation after free flap surgery is associated with comorbidities such as smoking, hypertension, and prolonged operation time [10-14]. In addition, the direct causes of reoperation and failure of free flaps include thrombosis, and the most important factor in the development of thrombosis is the technical ability of the surgeon [8,15]. There have been study on the effects of previous treatment on flap outcome through comparison between salvage surgery and primary surgery, there was no statistically significant effect [16]. But no studies have subdivided the previous treatment, the risk of performing microvascular anastomosis in the context of previous RT or surgery was not analyzed. As such, the aim of this study is to identify the risk factors for early complications, such as flap failure and re-exploration, and causes that required re-exploration after the microvascular anastomosis, especially previous treatments such as neck dissection or RT, using a single surgeon’s data.

CCRT and organ preserving surgery with adjuvant treatment have been preferred as initial treatment because they outperform radical surgery in functional outcomes and complications [1-3]. As a result, more cases of salvage surgery are required, and the number of cases of salvage surgery seems to be also increasing in this study, and microvascular anastomosis at sites which had previously undergone neck dissection and/or RT are likely to lead to early complications and re-exploration. In our study, the overall free flap success rate was 92.3%, which is similar to the previous literature reports, which range from 85% to 98% [5-9]. Up to 18.6% of patients underwent a re-exploration after free flap reconstruction, which is also similar to reoperation rate in free flap reconstruction surgery of head and neck reported by previous studies [11,12]. Previous studies have shown that several factors are associated with reoperation and free flap failure, such as previous treatment at the anastomosis site, cardiovascular diseases such as hypertension, angina pectoris, arteriosclerosis, and diabetes [8,10,13,15]. However, in the head and neck, few authors have confirmed that the previous treatment is a risk factor for re-exploration after free flap reconstruction [11,14]. The identification of the risk of performing microvascular anastomosis in previously treated neck can help surgeons better consult with patients and make such risks predictable. In the present study we analyzed the free flap reconstruction performed by a single surgeon to reduce the bias due to the differences between surgeons.

Many medical factors, such as comorbidities including cardiovascular disease, diabetes, obesity, and smoking history, may influence re-exploration and flap success [17,18]. However, in the present study, there was no significant correlation between age, sex, cardiovascular disease, diabetes mellitus, smoking, obesity, and re-exploration and free flap failure.

There have been some papers that compared the success rate of free flaps by donor site. Nakatsuka, et al. [19] have shown that flap survival rate for radial forearm, rectus abdominis, and jejunum flaps is significantly better than that of other flaps in a series of 2372 head and neck free flap reconstructions. However, Zhou, et al. [20] have concluded that there is statistically significant difference between the success rates in fibula flap, anterolateral thigh flap, and radial forearm flap groups. In our series, reconstruction with a flap that is rarely used like scapular, iliac crest and rectus abdominis flaps had higher failure and re-exploration rates and the surgeon’s familiarity for the flap may be an important factor influencing flap failure or re-exploration. Also, our analysis showed that surgery duration of more than 12 hours was an independent risk factors for re-exploration [OR=1.253 (95% CI 1.253-6.666, p=0.013)]. A prolonged anesthesia may set off a longer tissue ischemia, resulting in anoxic injuries [21]. Prolonged anesthesia also requires more fluid supply during surgery. Large amounts of crystalloid supplies during surgery also are associated with free flap complications [22]. Wong, et al. [23] have concluded that operative time is also significantly associated with increased risk for free flap failure in a study including 778 free flap operations. However, the prolonged operation time in this series may mean surgery with larger resection and complex reconstruction as these data are from a single surgeon and the meaning may be that difficult surgeries have a higher risk of re-exploration.

The main focus of this research was the effect of previous treatment in the field of microvascular anastomosis. As the RT is used frequently as primary treatment in many head and neck cancers, the influence of RT on the microvascular anastomosis became an issue in salvage surgeries. Radiotherapy is known to causes damage to blood vessels, which can cause blood flow reduction and thrombus formation and affect the outcome of the flap [24]. However the effect of previous irradiation at the anastomosis site on free flap failure remains controversial. Significant correlations between flap failures and previous RT in excess of total 60 Gy have been reported [25-27], but a study by Zhao, et al. [14] did not confirm the statistical relationship between radiotherapy within 30 days prior to surgery and reoperation. Further, in a study by Bengtson, et al. [28], there was no significant difference in the incidence of total free flap loss patients that received preoperative radiotherapy (5.3%) and those who did not (5.0%). In our analysis, microvascular anastomosis in terrains, where only RT had been performed, did not significantly increase the risk of flap failure or re-exploration. Although the risk of hematoma requiring re-exploration showed tendency to be higher than that of untreated necks [OR=3.536 (95% CI 0.979-12.767, p=0.053)], the risk of venous congestion was not affected by RT.

In contrast, the risk of re-exploration was significantly higher in patients earlier treated with both neck dissection and RT in whom microvascular anastomosis is performed. However, in case of previous neck dissection and RT, although the rate of flap failure was higher than in other groups, did not show any statistically significant difference in the risk of flap failure. In patients with a history of previous neck surgery, the formation of scar tissue and the vascular condition can affect the outcome of free flaps. In a study by Zhou, et al. [20], patients who had previous neck surgery (21.4%) had significantly higher failure rates than those who did not (2.7%) (p=0.007). In our study, the most common cause of re-exploration was venous congestion, and more venous congestion occurred in patients who received both neck dissection and radiotherapy before reconstruction surgery. Furthermore, hematoma was the second most common cause (33.3%) of re-exploration, and previous neck dissection with or without RT influenced the development of hematoma requiring re-exploration. Previous neck dissection significantly increased the incidence of hematoma, which may be due to the restriction of drain position due to the pedicle and vascular condition affected by the previous surgery, or the scar tissue and the vascular condition may have been more affected by the postoperative enoxaparine.

As in any retrospective review, this study had some limitations. the database does not contain detailed information on the previous treatment, pedicle status, so we were unable to study these items together as variables.

In conclusion, the flap failure rate did not increase significantly with microvascular anastomosis in previously treated patients, but re-exploration was frequently performed in patients who previously received both neck dissection and RT. In particular, venous congestion and hematoma, the most common causes of re-exploration, were more common in patients who previously underwent both neck dissection and RT. Microvascular anastomosis in the context of previous RT did not increase the risk of flap failure or re-exploration and seemed to be performed safely. Therefore, microvascular anastomosis in previously treated necks, especially those previously treated with RT only, looks feasible without increasing the risk of flap failure. However, the surgeon should check the previous treatment history of the patient and be aware that microvascular anastomosis in the neck where both neck dissection and radiotherapy were performed earlier may be more likely to cause venous congestion or hematoma. In the case of patients with history neck dissection and radiotherapy, careful intraoperative hemostasis and technique are required, and postoperative management should also be taken care of with the higher possibility of re-exploration.