Abstract
Objective
Prophylactic ligation of the external carotid artery (ECA) during oropharyngeal squamous cell carcinoma (OPSCC) resection is known to reduce severe postoperative oropharyngeal bleeding events, however, there is limited research on whether bleed rates vary between selective ligation of individual vessels or total ligation of the ECA. This study assesses outcomes related to total versus selective ligation of the ECA in patients who underwent transoral resection for OPSCC of the base of tongue or palatine tonsils.
Study Design
Retrospective review.
Setting
Patients who underwent OPSCC resection of the base of tongue or palatine tonsils at a single institution between October 2019 and September 2023.
Methods
Bleeding events within 30 days of surgery from the oropharyngeal surgical site were analyzed as well as other potential complications including stroke. Descriptive statistics and Fisher's exact test or χ 2 testing were used to analyze the data.
Results
Of 140 patients, 51 underwent base of tongue resection, and 89 had tonsillar resection. Total ECA ligation was performed in 56 patients, while 80 had selective ligation. There was no significant difference in oropharyngeal bleeding between the 2 groups (total 3.8% vs selective 3.7% P > .05). One patient in the total ECA ligation group had a stroke after resection (1.9%). On multivariate analysis, age (P = .024) and radiation exposure (P = .011) were found to be significant risk factors for hemorrhage.
Conclusion
Selective ligation of external carotid vessels versus total ligation of the ECA shows similar rates of oropharyngeal bleeding without any significant risk of stroke.
Keywords: bleeding, cancer, carotid ligation, complications, hemorrhage, oropharynx, transoral oropharyngeal surgery
The incidence of human papillomavirus (HPV)‐associated oropharyngeal squamous cell carcinoma (OPSCC) is increasing. 1 Minimally invasive surgical techniques allow for improved functional outcomes compared to HPV‐negative disease that is managed with radiation or chemoradiation as primary treatment. 2 Surgical complications include postoperative hemorrhage, gastrostomy tube dependence, aspiration, and lingual or hypoglossal nerve injury. 2 Postoperative hemorrhage is the most common complication with hemorrhage rates as high as 18.5%, and can require emergent airway management or even be fatal. 2 Prophylactic ligation of the ipsilateral external carotid artery (ECA) reduces life‐threatening postoperative hemorrhages. 3
There are 2 commonly used techniques for prophylactic ligation in transoral surgery: total ECA ligation or selective ligation of specific ECA branches. Total ECA ligation can be performed above the superior thyroid artery or include the entire ECA while selective artery ligation only ligates specific arteries supplying the tumor. 2 Prophylactic artery ligation is effective in reducing the incidence of major postoperative hemorrhage, but there is limited research into differences in bleed rates and complications in the different ligation techniques. 4 The aim of this study is to assess outcomes related to total versus selective ligation of the ECA or its branches in patients who underwent transoral resection for OPSCC of the base of the tongue or palatine tonsils.
Methods
We obtained approval from the Baylor Scott & White Institutional Review Board to perform a retrospective analysis of all patients who underwent transoral resection for OPSCC of the base of tongue or palatine tonsils at a single institution between October 2019 and September 2023. Resection techniques included both robotic resection and transoral laser resection. Patients were excluded if they did not have ligation of any branches of the ECA system. Clinical notes, operative notes, and postoperative course notes were reviewed. Selective or total ECA ligation data was collected from operative notes and all procedures were performed by 1 of 2 surgeons. Total ligation of the ECA was defined as ligation above or below the superior thyroid artery (Figure 1). Selective ligation of the ECA was defined as ligation of any branches, not including all branches of the ECA that were thought to feed the tumor (Figure 2). At least 2 branches of the ECA had to remain with selective ligation of the ECA. All primary tumor resections were performed at the same time as the neck dissection. Other independent variables included primary tumor oropharyngeal subsite, gastrostomy tube placement, stroke, and oropharyngeal hemorrhage. Reports of oropharyngeal hemorrhage rates were included in the analysis if they were from the primary oropharyngeal surgical site and within 30 days of surgery. All patients on anticoagulation therapy discontinued treatment 7 days before surgery and remained off anticoagulants for 2 weeks following the procedure. Any bleeding episodes unrelated to the primary oropharyngeal surgical site were excluded. Descriptive statistics and Fisher exact test or χ 2 test were used to analyze the data. P values of <.05 were considered significant.
Figure 1.
Total external carotid artery ligation.
Figure 2.
Selective external carotid artery ligation. The blue arrow indicates Superior thyroid artery ligation. The white arrow indicates lingual artery ligation. The black arrow indicates facial artery ligation. * indicates the hypoglossal nerve (CN XII).
Multivariate analysis was performed to determine which variables contributed to bleeding using multiple logistic regression analysis. Both demographic variables and outcome variables which had a P < .2 on univariate analysis were included in multivariate analysis. The integrity of the model was tested for collinearity and cross‐validated for goodness of fit using the Akaike information criterion to determine optimal model selection. All variables were initially included for model selection. Multiple regression analysis was only performed on variables that fit the optimum model while all others were excluded from this analysis.
Results
There were 136 patients who met the inclusion criteria for this study. 117 (86.0%) patients were male and 19 (14.0%) were female (Table 1). The site of transoral resection was the palatine tonsil in 85 patients (62.5%) or the base of the tongue in 51 patients (37.5%). The average age at surgery was 62.4 (SD = 10.8) years. The average duration of hospitalization was 5.81 (SD = 3.52) days. There was no significant difference in tumor size between the selective ECA ligation (M = 2.47 cm, SD = 1.08) and the total ECA ligation groups (M = 2.81 cm, SD = 1.33); t(126) = −1.61 [P = .055].
Table 1.
Patient Demographics
| Characteristic | Selective ECA ligation | Total ECA ligation | P value |
|---|---|---|---|
| Total, % | 80 (59) | 56 (41) | |
| Age, y (SD) | 62.8 (10.3) | 61.8 (11.6) | .573 |
| Sex | |||
| Male, % | 66 (82.5) | 51 (91) | .156 |
| Female, % | 14 (17.5) | 5 (9) | |
| Tumor site | |||
| Tonsil, % | 50 (62.5) | 35 (62.5) | 1 |
| Base of tongue, % | 30 (37.5) | 21 (37.5) | |
| History of radiation | |||
| Yes, % | 3 (4) | 0 | .268 |
| No, % | 77 (96) | 56 (100) | |
| Tumor size, cm | 2.47 | 2.81 | .055 |
| T classification | |||
| T1 | 27 | 18 | .354 |
| T2 | 42 | 25 | |
| T3 | 5 | 9 | |
| T4 | 0 | 1 | |
Abbreviation: ECA, external carotid artery.
In total, 80 patients underwent selective ECA ligation (58.8%) and 56 had total ligation (41.2%). In the selective artery ligation group, 80% of patients underwent ligation of the superior thyroid, lingual, and facial arteries, while the remaining 20% included ligation of the ascending pharyngeal artery. There was no significant difference in all oropharyngeal bleeding between patients who had selective ECA ligation (3/80, 3.75%) and patients who had total ECA ligation (2/56, 3.57%) [P = 1]. Three patients experienced minor bleeding which was observed without intervention. Two patients in the selective ECA ligation group experienced severe bleeding which was managed with cautery of the pharyngeal hemorrhage under general anesthesia (Table 2). There was 1 patient in the total ECA ligation group who had a stroke (1.79%) which occurred on Postoperative Day 5. There were no reported instances of pharyngocutaneous fistulas.
Table 2.
Details of Patients Who Experienced Postoperative Oropharyngeal Hemorrhage
| Age | Sex | Tumor size, cm | T stage | Tumor site | ECA ligation technique | Time from ligation to bleed, d | Treatment |
|---|---|---|---|---|---|---|---|
| 78 | M | 2.2 | 2 | BOT | Selective | 28 | Embolization |
| 61 | M | 2 | 1 | Tonsil | Selective | 7 | Cautery |
| 61 | M | 3.5 | 2 | Tonsil | Selective | 0 | Cautery |
| 64 | M | 3 | 2 | BOT | Total | 1 | Cautery |
| 84 | M | 2.2 | 2 | Tonsil | Total | 7 | Cautery |
Abbreviations: BOT, base on tongue; ECA, external carotid artery; M, male.
There were 3 patients total (3/136, 2.21%) who had prior head and neck radiation therapy. One of these patients experienced severe oropharyngeal hemorrhage (1/3, 33.3%), although this difference was not significant with the nonirradiated group (4/133, 3.01%) [P = .11]. Ten patients in the selective ECA ligation group had a gastrostomy tube placed after surgery (10/80, 12.5%) while there were 4 patients in the total ECA ligation group (4/56, 7.14%). This difference was not significant [P = .40]. A total of 114 cases underwent laser resection and 22 cases were treated with transoral robotic surgery (TORS). All bleeding events occurred in the laser resection group, however, this difference was not statistically significant [P = 1].
After adjusting for the best‐fit model, only age and radiation exposure were included in the regression analysis, and both variables were significantly associated with postoperative bleeding (age: coefficient = 0.003; 95% confidence interval [CI], 0.0004‐0.006; P = .024; radiation: coefficient = 0.28; 95% CI, 0.06‐0.49; P = .011) (Table 3).
Table 3.
Multivariable Regression Analysis for Transoral Postoperative Hemorrhage and Selected Variables
| Unadjusted multivariate OR (95% CI) | P value | Adjusted multivariate coefficientsa (9 5% CI) | P value | |
|---|---|---|---|---|
| Age | 1.14 (1.01‐1.29) | .028 | 0.003 (0.0004‐0.006) | .024 |
| Radiation history | 13.2 (0.74‐233) | .078 | 0.28 (0.06‐0.49) | .011 |
Abbreviations: AIC, Akaike information criterion; CI, confidence interval; OR, odds ratio.
AIC = −67.9.
Discussion
HPV‐associated OPSCC has superior survival rates to non‐HPV‐related head and neck cancers. 4 Minimally invasive surgical techniques can improve long‐term functional outcomes in these patients without compromising oncologic outcomes. Postoperative hemorrhage, however, remains a feared complication following minimally invasive transoral resection. 5 Because of this, techniques involving prophylactic ligation of the ECA have been developed to reduce hemorrhage rates. These techniques involve ligation of the lingual artery, facial artery, superior thyroid artery, ascending pharyngeal artery, ECA, or combinations of them. 6 , 7 , 8 Here, we found that there was no difference in hemorrhage rates between ligation techniques.
The most common complication of resection of OPSCC is postoperative hemorrhage with bleeding rates of 5.6% when treating patients with the laser and 5.9% with the robot. 7 Despite the low incidence of hemorrhage and even lower incidence of severe cases, it can lead to airway compromise, cardiac arrest, and death. Prior radiation, coagulopathies, and tumor stage are factors that increase the risk of hemorrhage. Several retrospective studies have investigated transcervical arterial ligation as a method to reduce these rates. A study of 265 patients who underwent robotic resection of OPSCC found transcervical arterial ligation significantly reduced postoperative bleeding, with rates of 1.3% in the ligation group compared to 7.8% in the nonligation group. 9 Another study found no difference in bleeding rates between groups with and without prophylactic ECA ligation, however, severe hemorrhage was only observed in the group without prophylactic ligation. 3 Kumar et al found an 8.7% hemorrhage rate and a 1.7% rate of severe hemorrhage leading to death in a study investigating transoral resection in HPV‐positive OPSCC using selective arterial ligation during neck dissection. 10
In our study, we showed similar, but overall low postoperative hemorrhage rates in both groups (5/136, 3.68%). This rate is within the range of other studies that examined hemorrhage rates in OPSCC resection with multiple primary surgical modalities (3.6%‐5.4%). 7 , 11 Pollei et al had a 15.6% documented ligation rate and did not find a significant difference in hemorrhage rates between the nonligated group. While the hemorrhage rates were not different, the authors note that tumors with higher T stages were significantly more likely to be ligated which may represent efforts to minimize bleeding in more complex wounds. Laccourreye et al only had 3 patients with prophylactic ligation of the ECA with no episodes of postoperative hemorrhage. The authors advise against prophylactic ligation of the ECA over concerns for impaired efficiency of postoperative radiation therapy due to increasing hypoxia levels at the tumor site as well as impeding arterial embolization if postoperative hemorrhage occurs. In a randomized clinical trial of transoral surgery for HPV‐positive OPSCC, Ferris et al mandated prophylactic transcervical ligation of arterial feeding vessels including ECA branches. 12 This was in response to a postoperative death from oropharyngeal bleeding when prophylactic ligation was not performed. After the mandate, there were no further deaths in the study. Although impaired efficiency of radiation therapy may be a concern for patients undergoing prophylactic arterial ligation, the benefits of preventing postoperative hemorrhage outweigh the potential drawbacks.
There were 2 episodes of severe bleeding in the selective ECA ligation group that had to be managed surgically. Collateral vessels may not demonstrate their contribution to hemorrhage until the postoperative period when the effects of ligation become more apparent. Selective ligation of the ECA may cause missed ligation of collateral vessels leading to hemorrhage at the surgical site. Theoretically, retrograde flow down the ECA can result in bleeding from intact branches, and endovascular embolization would be impossible in this circumstance with total ECA ligation. Despite these risks, clinical experience suggests that bleeding after total ligation is typically mild and manageable with cauterization or watchful waiting. In cases where bleeding persists, neck exploration would likely be required. Additionally, there were no pharyngocutaneous fistulas in our patient population.
There was 1 incidence of stroke in the total ECA ligation group. However, there is a lack of comprehensive data on the risk of stroke associated with prophylactic ECA ligation. Given this absence of research, it is more likely that other factors play a more significant role in stroke risk in patients undergoing head and neck surgery. The patient in our study presented with a left middle cerebral artery stroke five days after primary tonsil surgery. This patient did have hyperlipidemia and hypertension which are known risk factors for stroke. 13 Because of this, we believe established risk factors of stroke carry greater significance than prophylactic ECA ligation in determining stroke risk.
Prior studies have stated that a history of radiation is a strong predictor of postoperative hemorrhage. 3 , 9 Kubik et al found that a history of radiotherapy was a significant predictor of severe bleeding events following TORS. The incidence of severe bleeding in that study after TORS in irradiated patients was 14.6% versus 4.5% in nonirradiated patients (P < .02). They also found a trend toward reduced severe postoperative hemorrhage rates in irradiated patients with transcervical arterial ligation versus no ligation, however, this relationship was not statistically significant (P = .15). In our study, 3 patients in the selective ECA ligation group had a history of radiation, with 1 patient having an episode of severe bleeding in the postoperative period. On multivariate analysis, prior radiation and age were found to be significant risk factors for hemorrhage. This may indicate that prior radiation treatment makes patients more susceptible to hemorrhage due to the difficult nature of the fibrotic tissue. To minimize this risk, patients who have previous radiation to the head and neck usually undergo free flap reconstruction.
The ligation technique is surgeon‐specific, with most cases in our study undergoing selective ligation of important branches going toward the tumor. Both selective and total ligation techniques, however, are safe. Although there were 2 episodes of severe hemorrhage and 1 episode of stroke in our patient population, none of these incidents resulted in prolonged intubation or death. Future research could explore the long‐term effects of increased local tissue hypoxia in the context of ECA ligation on healing efficiency and postoperative radiation therapy efficacy.
There were limitations of this study. The retrospective design of the study was not powered to detect small differences in uncommon events. The ligation technique was obtained from the operative report of the surgeon which could have underestimated the number of patients in each group.
Conclusion
Prophylactic ligation of the ECA has been shown to reduce the incidence of severe hemorrhage following resection of oropharyngeal tumors. Although no difference in hemorrhage rate was detected between ligation techniques, the overall hemorrhage rate observed was low. As a result, detecting a meaningful difference would likely require a substantially larger sample size. While the choice of ligation technique may vary by surgeon, prophylactic ligation should be considered for all resections of oropharyngeal tumors that include concurrent neck dissection.
Author Contributions
Aaron Mackie, design, conduct, analysis, writing, editing, presentation; Lexi Goehring, design, conduct, writing, editing; Elizabeth Tuller, design, conduct, writing, editing; Dylan Lippert, design, editing; Lance Oxford, design, editing; Christopher Britt, design, conduct, analysis, editing.
Disclosures
Competing interests
None.
Funding source
None.
This article was presented as a poster at the AAO‐HNSF 2024 Annual Meeting & OTO Experience; September 28 to October 1, 2024; Miami, Florida.
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