Radiation therapy (RT) is an effective treatment method for head and neck cancer (HNC) and is a principal curative modality [1]. Most patients with HNC (80%; range, 73.9%–84.4%) receive RT [2]. Although RT is indispensable for HNC treatment, patients who are treated with RT experience acute or chronic side effects that include oral health deterioration, orocutaneous fistula formation, and osteoradionecrosis [3].

Orocutaneous fistula formation is a serious complication of RT that leads to wound infection, dysphasia, dysphagia, rupture of anastomotic vessels, and carotid blowout syndrome, which is defined as the rupture of the extracranial carotid artery or its branches, resulting in high morbidity and mortality [4-6]. Moreover, complications caused by a fistula can reduce a patient’s quality of life and make timely postoperative chemotherapy and radiotherapy administration difficult [7,8].

Wound healing in a previously irradiated neck region is often impaired by widespread scarring, fibrous tissue remodeling, and altered perfusion of irradiated tissues [9,10]. Consequently, fistula resolution in the irradiated neck region is difficult to achieve.

Improvement in patient outcome for the treatment of HNC complications depends on the selection of an appropriate surgical approach. In this study, we retrospectively reviewed our approaches for treating intractable fistulas that developed in seven patients after RT. We also discussed in detail the treatment methods used in two representative cases.

From 2009 to 2020, 62 cases received free tissue transfers for HNC reconstruction and 58 patients underwent surgery. A retrospective review of medical records was conducted to identify patients with fistulectomies and reconstructive surgeries for intractable fistulas. Patients who underwent RT were included. Patients were excluded from the study if they had undergone surgery for HNC and did not receive RT, or if their medical and clinical records were insufficient. A follow-up history of at least 1 year was a requirement for inclusion in the study.

The following data were analyzed with a retrospective observational study design: the number of surgeries, number of loco-regional surgeries, number of distant flap and free flap performed, number of additional surgeries needed after distant flap or free flap treatment, duration (months) from the first surgery to the last surgery, and type of surgery that led to fistula resolution.

This study was approved by the hospital’s institutional review board (IRB No. 2021-06-026) and was conducted in accordance with the principles of the Declaration of Helsinki. All participants provided written informed consent.

Seven patients (five males and two females) who were treated for fistulas from 2009 to 2020 were included in the study. Three patients had orocutaneous fistulas, two patients had oronasal fistulas, one patient had an esophagocutaneous fistula, and one patient had an oroantral fistula. One patient received preoperative RT, while six patients were treated with RT postoperatively. Three patients underwent chemotherapy with RT (Table 1).

Five loco-regional flaps, one distant flap, and one free flap were initially attempted for fistula repair; however, these procedures were unsuccessful. Six free flaps and one pedicled LDMC flap were the last surgeries performed in the patients. The last salvage reconstructions included two radial forearm free flaps, one fibular osteocutaneous free flap, and one anterolateral thigh free flap. Two patients received double free flaps that included: radial forearm flap and rectus abdominis flap, and fibular bone flap and anterolateral thigh flap (Table 1).

An average of 3.3±1.4 surgeries was required to resolve the fistulas and an average of 1.9±1.5 loco-regional surgeries and 1.4±0.5 distant flaps or free flaps were performed. Only three patients required additional surgery after distant flap or free flap. The mean time interval from the first surgery to the last surgery was 8.7±15.0 months. The failure rate of the loco-regional flap method was 100%; the combined distant flap and free flap failure rate was 30% (Table 2).

Despite clinical and medical advancements, the incidence of HNC is increasing and places a burden on public health due to the serious morbidity and mortality rates [13]. Recently, immediate elective repair using free tissue transfer has become an important treatment modality for reconstruction after HNC surgeries. Additionally, secondary free tissue transfer is used as a salvage method for the treatment of cancer recurrence, primary flap failure, or RT-related complications [14].

Distant flaps, such as the pectoralis major flap, deltoid flap, or latissimus dorsi flap, are still commonly used in reconstruction following HNC surgeries along with free tissue transfer. Distant flaps are also considered valid reconstruction tools when the primary free flap fails, or salvage reconstruction is needed due to other complications [15].

In contrast, loco-regional flaps can be used for small- to medium- sized defects of the head and neck; however, they are unsatisfactory for use in an irradiated field. RT elicits a series of inflammatory responses that lead to a radiation-induced fibroatrophic effect [16]. If the radiation-induced fibroatrophic effect occurs in a soft tissue around the neck, delayed wound healing can lead to fistula formation even when a free tissue transfer with good vascularity was used for reconstruction. These fistulas fail to heal with loco-regional flaps due to surrounding soft tissue fibrosis and impaired vascularity. In our study, all loco-regional flap surgeries failed. The combined failure rate of distant flap and free flap surgeries was 30%, and at least one distant flap or free flap was required to resolve the draining fistula.

Recipient vessel selection is limited in previously irradiated neck region. In these cases, the use of distant flaps such as PMMC flaps may be a suitable option for reconstructive surgery [17]. These flaps use multiple skin paddles and harvest muscle layers to reduce damage to the perforators, secure vascularity, and provide barriers to the fistulas. The use of distant flaps can shorten patients’ clinical courses and avoid unnecessary surgeries. The patient described in the first case lacked suitable recipient vessels in the neck for a successful free flap procedure (Fig. 1). Therefore, the reconstruction was performed with a pedicled LDMC flap that provided good vascularity. Although the patient’s fistula recurred once after the procedure, it was successfully treated with conservative measures.

Successful free tissue transfers are significant since they affect patients’ morbidity and mortality. Many factors are vital to the success of microscopic surgery; however, selecting an appropriate recipient vessel is one of the most significant factors [18]. In particular, patients with vessel-depleted neck who had undergone RT or a previous surgery lack suitable recipient vessels for free flap. At our institution, after checking the available recipient vessels using neck computed tomography angiography, the recipient vessels were selected outside the radiation field. The location of the soft tissue defect is the primary factor in the selection of recipient vessels. For upper head defects, the superficial temporal artery and vein or the middle temporal vein are the vessels of choice due to adequate caliber and ease of localization [19,20]. For lower head and neck defects, the superior thyroid artery and the external jugular vein are preferred, but these have often already been used for previous reconstructive surgery [21,22]. The facial or transverse cervical blood vessels can alternatively be used as another option for recipient vessels [18,23]. However, if these vessels are unavailable due to previous surgery or irradiation, the contralateral recipient vessels or distant flap should be considered [24]. In the second case presented in this study, the superficial temporal artery and middle temporal vein were used in the patient to resolve the oroantral fistula and the contralateral side vessels were used to resolve the orocutaneous fistula (Fig. 2). If all the methods are unfeasible, then the pectoral branch of the thoracoacromial artery or the internal mammary vessels can be used [25].

Due to the high loco-regional surgical failure rate, a distant flap or free flap with good vascularity is required for wound healing to occur. In addition, since the time interval between the first and last surgery is prolonged in these patients, unnecessary loco-regional surgery should be avoided. Therefore, if no improvement occurs after a sufficient period of conservative treatment, a distant flap or free tissue transfer should be considered for shortening the treatment periods and to reduce unnecessary surgeries for HNC patients who have undergone RT [26].

This study had several limitations. First, a selection bias may have occurred because of the retrospective study design. Second, there was an insufficient number of patients for a control group. Finally, statistical analyses could not be performed due to the small number of cases. Despite these limitations, we analyzed the appropriateness of the surgical treatments for the patients. Therefore, this study makes a valuable contribution for the small number of patients that require reconstructive surgery for intractable fistulas following RT for HNC.

Based on the study results, we suggest an approach to shorten patients’ treatment periods and reduce unnecessary surgeries for the treatment of fistulas that require reconstruction after RT for HNC. Free tissue transfers or distant flaps are often more invasive than loco-regional flaps and are difficult to perform [27]. However, when no improvement is achieved after a sufficient period of time with conservative management, free tissue transfers or distant flaps should be considered to shorten the treatment period.