From January, 2010 to December, 2019, 48 patients underwent TPLCE at Nara Medical University (Kashihara, Japan). A retrospective analysis of the clinical records was conducted and the incidence of TRN was calculated. Moreover, eight surgical techniques that may be used to prevent TRN were examined. The present retrospective study was approved by the Ethics Committee of Nara Medical University Hospital. Informed consent was obtained from all patients for the publication of the study and any accompanying images.

The patient information and clinical characteristics are presented in Table I. In total, 4 patients were female, and 44 were male. The mean age was 66 years (range, 44-86 years). In addition, 4 patients had oropharyngeal cancer, 34 patients had hypopharyngeal cancer, 5 patients had laryngeal cancer, and 5 patients had cervical esophageal cancer. The grading of the tumors in the present study as per the TNM classification system for cancers is presented in Tables II and III. In all patients, the tissue type was histopathologically confirmed as squamous cell carcinoma (9). The results of p16 immunohistochemical analysis were negative in all patients with oropharyngeal cancer.

A total of 13 patients underwent TPLCE as salvage treatment for recurrent or residual cancer following chemoradiotherapy (CRT) or radiotherapy (RT) alone or recurrent post-surgery. In addition, 7 patients underwent TPLCE following neoadjuvant chemotherapy. Docetaxel, cisplatin and 5-fluorouracil were administered as neoadjuvant chemotherapy. Cisplatin and 5-fluorouracil, cisplatin alone, carboplatin alone, or cetuximab alone were administered as CRT, and the irradiation dose ranged from 60-70 Gy. In total, 19 patients received post-operative RT or CRT due to the histopathological diagnosis, including extra-nodal spread and multiple cervical lymph node metastases. TRN as the necrosis of membranes or cartilage of more than one tracheal ring.

TPLCE was performed by a head and neck surgeon. All patients underwent reconstruction with a free jejunal transfer, which was performed to compensate for the defect of the cervical digestive tract and was harvested by an abdominal surgeon. Microvascular anastomosis of a free jejunal transfer was performed by a plastic surgeon. Finally, pharyngo-jejunal and jejunal-esophageal anastomoses were performed manually by head and neck surgeons. Although the extent of neck dissection was dependent on the location and size of lymph node metastasis in each patient, all patients underwent at least an ipsilateral neck lymph node dissection and paratracheal node dissection. In this surgery, the cutting lines were set at least 20 mm away from the margin of the tumor to ensure negative surgical margin. Therefore, in all cases, cervical esophagus was included in the resected tissue. In the first process, a collar incision was applied to all patients who underwent head and neck surgery as a cervical approach at Nara Medical University (Fig. 1).

In tumor resections, care is taken so as not to peel the esophageal membrane from the tracheal wall, as much as this is possible, with the exception of cases in which there is tumor invasion to the trachea in hypopharyngeal and laryngeal cancer and in the case of esophageal cancer. At the same time, while peeling this compartment, a scalpel was used instead of an electrocautery. These methods comprised the second process.

In the paratracheal operation, care was taken to preserve the branches of the inferior thyroid artery (ITA) as a third process (Fig. 2). When total thyroidectomy or lobectomy is required in some cases, the ITA is cut immediately in front of the thyroid gland. Hemostasis is performed as little as possible, particularly on the surface of the trachea, which indicates the fourth process. Immediately following TPLCE, a small part of the tracheal edge was cut to examine the blood supply to the trachea.

When forming the tracheal stoma, the subcutaneous incision after denudation was designed, as shown in Fig. 3A during the fifth process. The half-buried vertical mattress suture with non-absorbable thread was applied to form the tracheal stoma, and the sutures were performed at equal distances, which comprises the sixth process. First, the half-buried vertical mattress suture starts from the epidermal side to the tracheal side. The suture material crosses the wound and tracheal cartilage, similar to a regular vertical mattress suture. Second, the wound on the tracheal side did not cross when returning. Finally, the subcutaneous edge on the epidermal side was crossed, and a knot was made (Fig. 3B).

Surgical loupes magnification was used to view the images more clearly and closely. In addition, the already operated fields were covered with wet gauze to avoid drying. These are routinely performed to preserve the small vessels and are defined as the seventh and eighth processes.

The reasons for the development of TRN in the 3 patients in the present study were as follows:

Patient 1 had a cervical esophageal carcinoma close to the tracheal side (Fig. 5A). As the tumor had to be resected up to the closest to the tracheal wall, a number of ITA branches may have become damaged during this procedure, which indicates that the second and third processes were not fulfilled.

Patient 2 underwent anterior cervical discectomy and fusion, and had a plate and screws (Fig. 5B). These materials were close to the tumor that they needed to be removed at the same time. Therefore, the duration of the surgery was lengthy, and the blood supply and tissue may have been disrupted by dryness. Moreover, it was difficult to peel the laryngopharynx and cervical esophagus from the surrounding tissue due to the post-operative use of cicatrix due to anterior cervical discectomy and fusion. In this procedure, several branches of the ITA may have become damaged. A few days after the surgery, the free jejunum was necrotized. Although this patient was salvaged by tracheoplasty and pharyngostomy with a pectoral major musculocutaneous flap, some processes could not be performed, particularly the second and third, in the first surgery.

Patient 3 experienced TRN in only a small portion of one tracheal ring. The preservation of the blood supply to the trachea and the tissue around the tracheal stoma may be insufficient, although care was taken with these eight processes. Fortunately, the TRN improved only by application of an ointment.

In the present study, no patients experienced TRN following RT or CRT, and TRN developed immediately after surgery. It was thus considered that post-operative TRN mainly derived from the surgical procedure and these eight processes were played an important role in preserving the blood supply. These eight processes can be applied by any surgeons, and there are few recurrences around the tracheal stoma. In order to prevent TRN, the preservation of the branches of the ITA is essential. Although, in fact, there are some cases with unavoidable factors that may affect the development of TRN, such as thyroidectomy and paratracheal node dissection, the necessity of tracheal resection at a low level and the difficulty in surgery due to pre-operative tracheostomy, care is taken to preserve the blood supply to the trachea with the current surgical technique. The current surgical technique is effective at reducing the risk of developing TRN in cases with these factors as well.

Due to the retrospective nature of the present study, selection bias could not be avoided. Another limitation of the study is the severity of the disease. In other hospitals, surgeons may resect more aggressively owing to the advancement of the disease.

In conclusion, to date, only a limited number of studies have investigated TRN following TPLCE (6-8). The present study described the incidence of TRN at Nara Medical University and the surgical technique used. Knowledge regarding detailed anatomical structures and intraoperative exertion will lead to a decrease in the incidence of TRN. The authors hope that the surgical processes described herein may help numerous patients. Improved surgical techniques for the prevention of fatal complications need to be further investigated.