Microvascular Myocutaneous and Cutaneous Free Flap Reconstruction for Patients With Terminal Esophagostomy After Complicated Oncological Esophagus Resection

Abstract


Background
Esophageal cancer remains a rare diagnosis with limited prognosis in the western world. In Austria 423 patients were diagnosed with esophagus cancer in 2018. [1] Squamous cell carcinoma (SCC) and adenocarcinoma are the most frequently observed types of esophageal cancer with 5.2 per 100.000 for SCC and 0.7 per 100.000 for adenocarcinoma. SCC is most frequently observed in Asia whereas adenocarcinoma is more frequently observed in Europe, with rising incidence compared to SCC in recent years. [2] Medication based therapies for oncological diseases have rapidly improved over the years. [3] However, surgical esophagus resection is considered as gold standard treatment and as only potentially curative treatment option. Locally advanced tumors should receive neoadjuvant therapy to lower regiolocal recurrence rates and to ensure R0 resection. Widely used treatment options are neoadjuvant chemotherapies as well as neoadjuvant chemoradiation. In Europe currently the most commonly used neoadjuvant chemoradiation scheme is CROSS. Preoperative radiation is known to be an independent risk factor for local complications, complications appear more often especially when radiation dosage increases. [4][5][6] Typically, esophagus resection is followed by gastric tube pull-up reconstruction, either anatomical or extraanatomical retrosternal pull-up. SCC usually requires McKeown esophagectomy with cervical anastomosis, and adenocarcinoma can more often be treated by Ivor-Lewis esophagectomy with intrathoracic anastomosis. Minimal invasive operation techniques have improved patient outcome lately, yet esophagus resection remains a procedure with high mortality and morbidity. Especially anastomosis insu ciency remains a major problem. In patients with SCC who received cervical anastomosis prognosis depends on limitation to cervical region or further intrathoracic manifestation if insu ciency appears. Thoracic manifestation is associated with higher mortality and morbidity. Major reason for persisting anastomotic leakage is gastric pull-up tube necrosis. This complication appears scares, approximately 1% of esophagus resections with gastric pull-up lead to necrosis of gastric conduit with need for surgical revision. [7] Further used reconstruction techniques are colonic interposition or interposition of small bowel. Colonic interposition requires more anastomosis, which increases risk of anastomotic leak. Therefore, it is less frequently used.
[8] However, treatment options are scarce if secondary interposition develops necrosis as well or stulation occurs and sometimes terminal esophagostomy is the only solution. [9,10] This condition is associated with poor quality of life due to impossibility of oral intake. Quality of life is most impacted by possibility of oral nutrition, even in jejunum interposition quality of life is described to improve signi cantly. [11] Need for in-hospital-stay is frequent and therefore associated with high costs.
Despite multiple reconstructive approaches proposed in the past, there remains no consensus for the optimal method of reconstructing a terminal esophagostomy. [5,10,12,13]. Especially in patients after complicated postoperative course who received preoperative radiotherapy and are without treatment options. Microvascular myocutaneous and cutaneous free ap reconstruction could be a promising alternative for such patients. The use for esophageal reconstruction has already been described previously. [13] Free ap reconstruction has also been described as successful technique for reconstruction of complex mediastinal tracheal defects. [14] The aim of this paper is to analyze the outcome of microvascular myocutaneous and cutaneous free ap reconstruction for patients with terminal esophagostomy respectively persisting cervical anastomotic leak after complicated oncological esophagus resection for SCC at our surgical department.

Patients And Methods
We performed a retrospective analysis of all patients who received MFF reconstruction between March 2017 and November 2020 at University Hospital Salzburg in cooperation of Department of Surgery and Department of Oral and Maxillofacial Surgery.
The protocol for the research project has been approved by Ethics Committee of the institution within which the work was undertaken, and it conforms to the provisions of the Declaration of Helsinki in 1995 (as revised in Edinburgh 2000). Informed consent was obtained from all subjects. The research project was undergone without any nancial assistance and there are no relationships that may pose con ict of interest.
In the study period 7 patients were treated. All patients who received MFF reconstruction were male. Six patients initially received oncological esophagus resection because of SCC, one patient initially received hypopharyngeal resection after SCC diagnosis followed by esophageal resection because of esophageal recurrence. Gastric pull-up was performed in all seven patients. Secondary carcinoma was diagnosed in three out of seven patients (42.8%) at staging procedure with hypopharynx being the most common location. Postoperatively all patients developed severe complications leading salivary stomata operation. Endoscopic therapies like Endo-VAC, endoscopic dilatation and continuous endoscopic monitoring over short period of time was performed. Additionally four patients received colon interposition. Furthermore, one patient received jejunum interposition after developing necrosis of colonic interposition. Endoscopic and open vacuum-pressure therapy (VAC) was performed in six patients (85.7%). Indication for primary MFF replacement after gastric pull-up necrosis was imposed in two patients because of tracheal stulation.  T3 stadium was most frequently observed. Complete data was available in 6 out of 7 patients. All patients received reconstruction with microvascular myocutaneous and cutaneous free ap, the used free aps are reported in Table 2. The aps were used to restore continuity of oral cavity and esophagus. This was achieved by harvesting the ap at rst with su cient length of appertain vessels (e.g. Figure 1.1, 1.2, 1.4, 2.1). After a successful checking for su cient perfusion, the ap was transferred to the neck (e.g. Figure 1.3, 2.3, 2.4.). The ap was disposed in a circular form (e.g. Figure 1.3, 2.2) and then connected to gastric conduit or colonic interposition.
The used vessels for microvascular anastomosis are reported in Table 3.

Complications and patient contentment
Complications were obtained according to Clavien-Dindo Classi cation. Additionally, we evaluated patient contentment after surgical procedure with three questions ("Are you able to swallow appropriately?" "Did your Quality of Life improve, stay steady or worsen since operation was performed?" "With the knowledge now, would you consent in this procedure again?").

Graft results
MFF function was adequate in six out of seven patients (85.7%); ap necrosis appeared in one patient (14.3%). Flap results were initially good in ve patients, one more patient needed surgical revision to ensure graft function. No local complications appeared after free ap mobilization. Speaking was not feasible in both patients with tracheal stulation, one patient regained speaking ability, one patient can speak with appropriate tracheal canula. Patient with osteomyocutaneous free ap from medial femoral condyle developed satisfactory result: no complications were obtained and full ability of speaking was regained by the patient. Lateral-arm-ap was rejected, yet this graft choice can be applicated.

Complications and patient contentment
Of six patients four reported improved quality of life, results of the three questions are reported in Table 4.

Discussion
The results of this paper shows that MFF free ap is a safe and feasible treatment option for patients with terminal esophagostomy after complicated oncological esophagus resection. There was no procedure related mortality observed and only one patient reported worsening of quality of life while patients with su cient graft function reported massive regain of quality of life. Therefore, especially due to high subjective level of suffering and low quality of life this procedure can be considered. Despite the occurred complications and insu cient results in some patients, all patients besides one would consent into this treatment option again. That implicates the subjective poor quality of life prior to surgery. Number of patients who regained the ability of oral food intake was encouraging, especially in consideration of few other available treatment option with permanent need for cervical esophagostomy. Adequate graft function resulted in a signi cant improvement of quality of life for the patients. None patient reported lower quality of life than before free ap reconstruction. Anterior lateral thigh (ALT) free ap reconstruction is a frequently used free ap reconstruction technique for head and neck reconstructions, since its initial description in 1983. [15] However, free aps with vascularized bone components are described to deliver better results due to a lower risk of reabsorption. Free ap harvesting from the medial knee are performed since the early 1990s and can be used for reconstruction of postoperative defects, especially after tumor resection. However, vascular anatomy may diverge. Therefore, routinely preoperative vascular imaging is required before ap harvesting. [16,17]. Radial forearm free aps are also commonly used for reconstructions in the head and neck area. Still, free ap failure is a scarce but occurring problem. Graft failure is differentiated in early and late graft failure, with failure after seven postoperative day of surgery considered as late failure. The most important risk factor for graft failure is preoperative irradiation. Most frequent observed reasons for late graft failure are abscess formation and vascular compromise. Careful graft observation is recommended within the rst 14 postoperative days to detect graft dysfunction early. [18,19] Unfortunately, one graft was initially rejected in our group. Due to small size of total sample, some grafts were only used once. Result of graft does therefore not implicate about general outcome. Flaps for reconstruction should be selected individually and mutually with the patient. Rejection of graft remains a rare but occurring problem with few possible preventions. Treatment options are ending in patients with multiple failed reconstruction techniques after esophagus resection. Therefore, every further applied strategy needs to be well considered and discussed with the patient. MFF reconstruction offers an additional treatment option for those patients. However, this procedure has high-risks with numerous possible complications. Patients eligible for this treatment should be selected carefully and perioperative risks have to be reduced preoperatively for example by adequate monitoring of diabetes and su cient hemoglobin levels.
This study has potential limitations. We performed MFF reconstruction on a rather small patient sample.
Furthermore, this presentation is retrospective which is known for limitations like in this case the analysis of quality of life and available data of patients treated extramurally in detailed demographic data and primary tumor stadium.
However, the outcome of the patients after MFF reconstruction in this paper shows that the method might be a relevant treatment option to be discussed with patients if expertise in free ap reconstruction and esophageal surgery is available at primary treatment center.
In conclusion MFF reconstruction can be an alternative treatment option in patients with complicated postoperative courses with failing of primary reconstruction. MFF reconstruction has its role in patients with special defects like tracheal stulation or as option after conventional strategies failed. Due to ending therapy strategies newly applied strategies need to be discussed in detail with all bene cial and possible adverse aspects with the patient. For patients without further feasible treatment options MFF reconstruction is a promising alternative to improve quality of life. Figure 1 Intraoperative pictures of ALT reconstruction (1.1 harvesting of ALT free ap, 1.2. vessel preparation, 1.3. placement of ALT as interposition to ensure esophagus continuity with placed gastric tube, 1.4. nished placement of ALT with newly functionating esophagus)