Origin and treatment of the nasopharyngeal hemorrhage

Among the 17 cases, sphenopalatine artery bleeding was found in two patients, and posterior nasal septal artery bleeding was identified in one patient. These three patients were treated by endoscopic nasopharyngeal electrocoagulation and hemostasis.

Eleven patients were treated by digital subtraction arterial angiography embolization. These included seven patients with bleeding sites on the external carotid artery branches, such as intra-maxillary arteries, facial arteries, and ascending pharyngeal artery (Figures 1–4), 2 patients with vascular hemorrhage caused by internal carotid artery stenosis, and two patients with hemorrhage resulting from the rupture of a pseudoaneurysm in the internal carotid artery (Figures 5 and 6). The bleeding sites were identified by the bilateral external carotid artery and internal carotid artery angiography in which the contrast-enhanced Seldinger technique was used to percutaneously puncture the right femoral artery with a 4F or 5F Cobra catheter or a multipurpose catheter. Embolization approaches were chosen based on the results of angiography. External carotid artery branches were embolized with a steel coil alone, a steel coil plus gelatin sponge, or a steel coil together with polyvinyl alcohol particles. Internal carotid artery embolization was achieved using a removable balloon with a closed-cell stent. Eight (72.7%) of these 11 patients underwent single intervention, 2 patients received a double intervention and one required triple intervention. After interventional treatment, 81.8% (9/11) of patients had bilateral maxillofacial pain, pharyngeal numbness, and difficulties in opening the mouth. The symptoms improved significantly after hormone-assisted treatment for half a month and had entirely resolved after one month.


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Patient outcomes

Thirteen of the 17 patients were successfully rescued, whereas four died. Six months of follow-up in the 13 surviving patients showed no recurrence of hemorrhage. Of the four patients who died, 2 patients died of hemorrhagic shock, and 1 died of suffocation resulting from the blocking of the airway by blood clots. The fourth patient had blood clots blocking the airway after the hemorrhage but was saved by an emergency tracheotomy. The patient was then sent to the interventional theater for emergency digital subtraction angiography embolization and transferred to the intensive care unit for postoperative treatment. The patient subsequently died due to systemic multiple organ failure. The clinical stages of all four deaths were relatively late, with one in stage III and the other three in stage IV.

DISCUSSION

While radical radiotherapy represents the primary and most effective approach to treat NPC, the adverse effect of radiation on the adjacent healthy tissues remains to be resolved. Nasopharyngeal bleeding can be caused by tumor ulceration, necrosis, shedding, or mucosal hyperemia during radiotherapy.8 In the present study, 17 cases of nasopharyngeal hemorrhage after radiation treatment for NPC were collectively reviewed, and the rescue and management strategies were discussed.

Multiple physico-pathological factors contribute to nasopharyngeal hemorrhage. Patients of older age, with advanced disease, or who receive higher irradiation doses are more likely to develop nasopharyngeal bleeding after radiotherapy.9 Among the 17 patients recruited in this study, only two had stage II NPC, whereas 5 and 10 patients had stage III and IV disease, respectively. Nasopharyngeal hemorrhage is also associated with repeated radiotherapy, which is the major treatment for recurrent NPC.10 Among the complications of radiotherapy for NPC, nasopharyngeal hemorrhage was reported to account for 77.8%.11 Spreading more extensively in the skull base than the primary tumor, recurrent NPC requires an increased irradiation area and dose, which cause more damage to the surrounding tissues and increase the chance of nasopharyngeal hemorrhage. Consistently, in this study, seven patients suffered from recurrent NPC and underwent a second course of radiotherapy. In addition, fibrosis of the nasopharyngeal-cranial base tissue after radiotherapy increases the brittleness of blood vessels and hampers tissue repair, triggering long-term ulceration and necrosis.12 Patients with NPC may have nasal and nasopharyngeal mucosal atrophy after radiotherapy, resulting in reduced mucus production and dryness of the mucous membranes. Furthermore, radiotherapy destroys the motor function of the nasal and nasopharyngeal cilia and weakens the self-cleaning of the nasal cavity and nasopharynx. This increases the occurrence of radiotherapy-induced rhinosinusitis and retention of the nasopharyngeal secretions, leading to infections and inflammation, which are associated with damage to the nasopharynx.13Extensive tissue necrosis and erosion of the skull base bone result in the exposure and loss of major blood vessels in the nasopharynx, thereby causing potentially fatal hemorrhage. Moreover, the blood vessels may not be effectively repaired and occluded after the removal, by radiotherapy, of NPC cells that invade the blood vessels, causing spontaneous rupture and heavy bleeding.14

A shorter incubation period has been reported previously in patients of older age, with advanced disease, or repetitive irradiation.15 Among the 17 patients included in this study, nasopharyngeal hemorrhage occurred between 6 months and 8 years after radiotherapy, suggesting that NPC patients treated by radiotherapy need to remain alert to nasal bleeding over a long period. This is of importance despite advances in radiotherapy technologies that have reduced the local residual rate of NPC and the complications of radiotherapy and improved the efficacy of radiotherapy.16 Stereotactic radiosurgery and adaptive IMRT have been reported to increase the chance of nasopharyngeal hemorrhage, while both reduce the local residual rate of NPC and the occurrence of complications.17

The amount of hemorrhage after nasopharyngeal radiotherapy ranges from dozens to thousands of milliliters, and massive hemorrhage can be lethal within a short period. The likelihood of post-radiotherapy nasopharyngeal hemorrhage in patients with NPC can be assessed by the rate and frequency of symptomatic bleeding and the CT imaging results, which indicate the extent of damage to the nasopharynx and skull base. Patients with frequent or increased symptomatic nasal or oral bleeding, or CT images showing nasopharynx–skull base damage involving the adjacent blood vessels, require close observation and easy accessibility to rescue equipment. In the management of nasopharyngeal hemorrhage, maintaining upper airway patency is critical. Mucus suction, endotracheal intubation, and tracheotomy are approaches of choice depending on the upper airway patency. Once the bleeding sites are identified, anterior and posterior nostril packing, endoscopic nasopharynx electrocoagulation, and digital subtraction angiography embolization can be performed to stop the nasopharyngeal bleeding.

In summary, post-radiotherapy nasopharyngeal hemorrhage is often caused by erosion of the internal carotid artery and maxillary artery. Anterior and posterior nostril packing, endoscopic nasopharynx electrocoagulation, and digital subtraction angiography embolization are effective approaches for managing nasopharyngeal hemorrhage.

Acknowledgment

This study was supported by the Natural Science Foundation of Hainan Province, China (No. 818MS130). The authors thank all the patients and the research staff for their contributions to this project.

Disclosure

The authors report no conflicts of interest in this work.


Jiabin Zhan,1,* Shuai Zhang,2,* Xin Wei,1 Yihui Fu,3 Jing Zheng1

1Department of Otolaryngology, Hainan General Hospital, Haikou 570311, Hainan, China; 2Department of Radiation Oncology, Hainan General Hospital, Haikou 570311, Hainan Province, China; 3Department of Respiratory Medicine, Hainan General Hospital, Haikou 570311, Hainan Province, China

*These authors contributed equally to this work.


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Source:Cancer Management and Research.

Originally published March 15, 2019.

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