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Necrosis of the tongue after arterial chemotherapy
Necrosis of the tongue after arterial chemotherapy CHANG-TE SHIH, MD, SHENG-PO HAO, MD, SHU-HANG NG, MD, and KAI-CHENG LAWRENCE YEN, MD,
Taipei, Taiwan, Republic of China
Necrosis of the tongue is an uncommon clinical finding because the tongue is highly vascular and well supplied from the right and left lingual arteries. Temporal arteritis is the most common cause of necrosis of the tongue.1 Cases of necrosis of the tongue have been reported sporadically.2-4 Herein we report a case of necrosis over one half of the tongue in a patient with buccal cancer as a complication of intraarterial chemotherapy. CASE REPORT A 52-year-old man came to our clinic because of a painful tumor in the right buccal mucosa in January 1996. He was a smoker, and he had also chewed betel nuts for 30 years. He did not have a history of hypertension, diabetes, or autoimmune disease. Examination revealed an ulcerative tumor over the right buccal mucosa (7 × 5 cm in size) with right submandibular lymphadenopathy (T4N2bM0). There was no lesion in the tongue. A biopsy specimen from the buccal lesion showed a well-differentiated, keratinized squamous cell carcinoma. The patient underwent intraarterial chemotherapy by way of a catheter implant through a puncture in the right femoral artery on February 2, 1996. An angiogram demonstrated a hypervascular mass with a tumor stain in the right buccal region predominantly supplied by the right facial artery, and the lingual artery was well delineated (Fig 1). The catheter was placed in the orifice of the right facial artery for intraarterial chemotherapy and was anchored with adhesive tape over the right thigh. The chemotherapy regimen consisted of cisplatin (100 mg/m2 for 3 hours on day 1) and 5-fluorouracil (5-FU; 1000 mg/m2/day for 4 days). The patient thought that the catheter was displaced during the procedure and had a burning sensation over his right hemiface and tongue when cisplatin was infused on day 1. Two days later, the patient reported severe pain and swelling of the tongue. At that time 5 mg of dexamethasone was injected intravenously.
From the Departments of Otolaryngology (Drs. Shih and Hao) and Radiology (Dr. Ng), Chang Gung Memorial Hospital, Chang Gung University; and the Section of Otolaryngology–Head and Neck Surgery (Dr. Yen), Sun Yat-Sen Cancer Center. Taipei, Taiwan, Republic of China Reprint requests: Sheng Po Hao, MD, Department of Otolaryngology, Chang Gung Memorial Hospital, 5 Fu-Hsing St, Kwei-Shan, TaoYuan 333, Taiwan, R.O.C. Otolaryngol Head Neck Surg 1999;121:655-7. Copyright © 1999 by the American Academy of Otolaryngology– Head and Neck Surgery Foundation, Inc. 0194-5998/99/$8.00 + 0 23/78/90099
He had dysphagia and dyspnea the next day. The tongue turned blue, the catheter was removed, and 10 mg of dexamethasone was administered. The intraarterial infusion of 5FU was changed to the intravenous route. The accumulated dosage of 5-FU infused was 3300 mg intraarterially and 3900 mg intravenously. There was an ulceration on the swollen tongue on day 4. On day 7, the right side of the tongue was noted to be black. A follow-up angiogram of the right external carotid artery on March 6, 1996, poorly delineated the lingual artery (Fig 2). He underwent debridement of the necrotic tissue in March 1996. The entire right side of the tongue was removed (Fig 3). Then, he underwent thorough excision of the right buccal cancer, together with marginal mandibulectomy and right modified radical neck dissection on March 12, 1996. After 11 months of follow-up, he had a local recurrence and died of massive bleeding on May 12, 1997. DISCUSSION Necrosis of the tongue is rare because the tongue has a very rich blood supply from the right and left lingual arteries. Temporal arteritis is the most common cause of tongue necrosis at present.1 There are sporadic cases of necrosis of the tongue from causes such as paraneoplastic syndrome,2 radiotherapy followed by radical neck dissection,3 vasculitis,4 and systemic lupus erythematosus.5 Regional intraarterial chemotherapy in the treatment of cancer of the head and neck has been reintroduced recently, more than four decades after the pioneer work of Klopp et al.6 The therapeutic advantage gained by the use of intraarterial chemotherapy is that the tumor/normal tissue blood flow ratio favors drug delivery to the tumor and overcomes the systemic toxicity from high-dose chemotherapy.7 Cisplatin is a platinum compound and is one of the most effective chemotherapeutic agents in head and neck cancer. The antimetabolite 5-FU is also commonly used in many combination regimens including cisplatin and as a single agent. The complications from intraarterial infusion therapy in head and neck cancers are classified into two categories: (1) chemotherapy-associated problems, and (2) catheter-related morbidity. In the past the catheter-related complications were as high as 75%.8 The reported technical complications of intraarterial chemotherapy include failure to catheterize, neurologic symptoms, a clotted catheter, dislodgment of the catheter tip, subcutaneous soft tissue necrosis, infection, hemorrhage, embolism, and arterial spasm.8-10 Although the technique of catheterization and materials used in the catheter have improved recently, catheter-related complications can be up to 30%.9 To our knowledge, no case of 655
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Fig 3. Necrosis involving right half of the tongue.
Fig 1. Right common carotid angiogram showed normal lingual artery filling (arrow).
Fig 2. Right common carotid angiogram performed after chemotherapy showed occlusion of the proximal lingual artery (arrow).
necrosis of the tongue after intraarterial chemotherapy has been previously reported. The lingual artery classically arises as the third branch from the external carotid artery. Homze et al.11 found 4 cases in 91 dissections in which the lingual artery arose with the facial artery as a lingual-facial trunk. Our patient, who had advanced buccal cancer, underwent transfemoral catheterization to the external carotid artery just proximal to the orifice of the facial artery, and no lingual-facial trunk was seen (Fig 1). However, the patient believed that the catheter was displaced and also felt a burning sensation in the tongue during the infusion of cisplatin just a few hours after initial catheterization. Before removal of the catheter, he received a total intraarterial infusion of 3300 mg 5-FU. Perhaps the tip of the catheter became dislodged into the lingual artery after catheterization. It is possible that the catheter caused spasm of the lingual artery as Lee et al.10 described on angiogram or embolization developed after dislodgment of the catheter. In addition to the catheter-related complications, cisplatin-based chemotherapy may have resulted in major arterial occlusion12 and autonomic neuropathy with potentiation of arterial spasm.13 5-FU can also cause arterial endothelial wall damage.14 These factors may have played a role in embarrassing the blood supply to the tongue. Although the tongue receives its blood supply from both lingual arteries, there is no marked anastomosis between the lingual arteries except at the tip and base of the tongue and the submucosal surface.15 Intraarterial chemotherapy is an alternative treatment for advanced head and neck cancer. However, it is invasive, and the long-term indwelling catheter should be carefully anchored. Although the procedure has been developed for more than 40 years, it still possesses certain morbidity and mortality. The treating physician should be aware of the position of the catheter tip and condition of patient during the course of treatment to prevent severe and irreversible complications. When dislodgment of the catheter is noted, chemotherapy should be stopped and the catheter withdrawn immediately.
Otolaryngology– Head and Neck Surgery Volume 121 Number 5
REFERENCES 1. Pendás SL, De Vicente Rodríguez JC, González García M, et al. Tongue necrosis as a complication of temporal arteritis. Oral Surg Oral Med Oral Pathol 1994;78:448-51. 2. Park SS, Karp DD, Karmody CS. Lingual necrosis as the initial symptom of small cell carcinoma. Otolaryngol Head Neck Surg 1995;112:782-4. 3. Gault DT. Tongue necrosis after radical neck dissection. Head Neck Surg 1988;10:344-5. 4. Ekman-Joelsson BM, Kjellman B, Hattevig G. Tongue necrosis due to vasculitis. Acta Paediatr 1995;84:1333-6. 5. Korn S, Huppert A, Spitzer S, et al. Systemic lupus erythematosus presenting with lingual infarction. J Rheumatol 1988;15: 1281-3. 6. Klopp CT, Alford TC, Bateman J, et al. Fractionated intraarterial cancer chemotherapy with methyl bis amine hydrochloride: a preliminary report. Ann Surg 1950;132:811-32. 7. Wheeler RH, Ziessman HA, Medvec BR, et al. Tumor blood flow and systemic shunting in patients receiving intraarterial chemotherapy for head and neck cancer. Cancer Res 1986;46:4200-4. 8. Donegan WL. Regional infusion chemotherapy for cancer of the head and neck. Surgery Annual 1975;7:137-73.
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9. Cheung DK, Regan J, Savin M, et al. A pilot study of intraarterial chemotherapy with cisplatin in locally advanced head and neck cancer. Cancer 1988;61:903-8. 10. Lee YY, Dimery IW, Tassel PV, et al. Superselective intra-arterial chemotherapy of advanced paranasal sinus tumors. Arch Otolaryngol Head Neck Surg 1989;115:503-11. 11. Homze EJ, Harn SD, Bavitz BJ. Extraoral ligation of the lingual artery, an anatomic study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997;83:321-4. 12. Doll DC, List AF, Greco FA, et al. Acute vascular ischemic events after cisplatin-based combination chemotherapy for germ-cell tumors of the testis. Ann Intern Med 1986;105:4851. 13. Rosenfeld CS, Broder LE. Cisplatin-induced autonomic neuropathy. Cancer Treatment Reports 1984;68:659-60. 14. Cwikiel M, Zhang B, Eskilsson J, et al. The influence of 5-fluorouracil on the endothelium in small arteries. An electron microscopic study in rabbits. Scanning Microsc 1995;9:56176. 15. Zimmerman RA, McLean G, Freiman D, et al. The diagnostic and therapeutic role of angiography in lingual arterial bleeding. Radiology 1979;133:639-43.
Taipei, Taiwan, Republic of China
Necrosis of the tongue is an uncommon clinical finding because the tongue is highly vascular and well supplied from the right and left lingual arteries. Temporal arteritis is the most common cause of necrosis of the tongue.1 Cases of necrosis of the tongue have been reported sporadically.2-4 Herein we report a case of necrosis over one half of the tongue in a patient with buccal cancer as a complication of intraarterial chemotherapy. CASE REPORT A 52-year-old man came to our clinic because of a painful tumor in the right buccal mucosa in January 1996. He was a smoker, and he had also chewed betel nuts for 30 years. He did not have a history of hypertension, diabetes, or autoimmune disease. Examination revealed an ulcerative tumor over the right buccal mucosa (7 × 5 cm in size) with right submandibular lymphadenopathy (T4N2bM0). There was no lesion in the tongue. A biopsy specimen from the buccal lesion showed a well-differentiated, keratinized squamous cell carcinoma. The patient underwent intraarterial chemotherapy by way of a catheter implant through a puncture in the right femoral artery on February 2, 1996. An angiogram demonstrated a hypervascular mass with a tumor stain in the right buccal region predominantly supplied by the right facial artery, and the lingual artery was well delineated (Fig 1). The catheter was placed in the orifice of the right facial artery for intraarterial chemotherapy and was anchored with adhesive tape over the right thigh. The chemotherapy regimen consisted of cisplatin (100 mg/m2 for 3 hours on day 1) and 5-fluorouracil (5-FU; 1000 mg/m2/day for 4 days). The patient thought that the catheter was displaced during the procedure and had a burning sensation over his right hemiface and tongue when cisplatin was infused on day 1. Two days later, the patient reported severe pain and swelling of the tongue. At that time 5 mg of dexamethasone was injected intravenously.
From the Departments of Otolaryngology (Drs. Shih and Hao) and Radiology (Dr. Ng), Chang Gung Memorial Hospital, Chang Gung University; and the Section of Otolaryngology–Head and Neck Surgery (Dr. Yen), Sun Yat-Sen Cancer Center. Taipei, Taiwan, Republic of China Reprint requests: Sheng Po Hao, MD, Department of Otolaryngology, Chang Gung Memorial Hospital, 5 Fu-Hsing St, Kwei-Shan, TaoYuan 333, Taiwan, R.O.C. Otolaryngol Head Neck Surg 1999;121:655-7. Copyright © 1999 by the American Academy of Otolaryngology– Head and Neck Surgery Foundation, Inc. 0194-5998/99/$8.00 + 0 23/78/90099
He had dysphagia and dyspnea the next day. The tongue turned blue, the catheter was removed, and 10 mg of dexamethasone was administered. The intraarterial infusion of 5FU was changed to the intravenous route. The accumulated dosage of 5-FU infused was 3300 mg intraarterially and 3900 mg intravenously. There was an ulceration on the swollen tongue on day 4. On day 7, the right side of the tongue was noted to be black. A follow-up angiogram of the right external carotid artery on March 6, 1996, poorly delineated the lingual artery (Fig 2). He underwent debridement of the necrotic tissue in March 1996. The entire right side of the tongue was removed (Fig 3). Then, he underwent thorough excision of the right buccal cancer, together with marginal mandibulectomy and right modified radical neck dissection on March 12, 1996. After 11 months of follow-up, he had a local recurrence and died of massive bleeding on May 12, 1997. DISCUSSION Necrosis of the tongue is rare because the tongue has a very rich blood supply from the right and left lingual arteries. Temporal arteritis is the most common cause of tongue necrosis at present.1 There are sporadic cases of necrosis of the tongue from causes such as paraneoplastic syndrome,2 radiotherapy followed by radical neck dissection,3 vasculitis,4 and systemic lupus erythematosus.5 Regional intraarterial chemotherapy in the treatment of cancer of the head and neck has been reintroduced recently, more than four decades after the pioneer work of Klopp et al.6 The therapeutic advantage gained by the use of intraarterial chemotherapy is that the tumor/normal tissue blood flow ratio favors drug delivery to the tumor and overcomes the systemic toxicity from high-dose chemotherapy.7 Cisplatin is a platinum compound and is one of the most effective chemotherapeutic agents in head and neck cancer. The antimetabolite 5-FU is also commonly used in many combination regimens including cisplatin and as a single agent. The complications from intraarterial infusion therapy in head and neck cancers are classified into two categories: (1) chemotherapy-associated problems, and (2) catheter-related morbidity. In the past the catheter-related complications were as high as 75%.8 The reported technical complications of intraarterial chemotherapy include failure to catheterize, neurologic symptoms, a clotted catheter, dislodgment of the catheter tip, subcutaneous soft tissue necrosis, infection, hemorrhage, embolism, and arterial spasm.8-10 Although the technique of catheterization and materials used in the catheter have improved recently, catheter-related complications can be up to 30%.9 To our knowledge, no case of 655
656
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Otolaryngology– Head and Neck Surgery November 1999
Fig 3. Necrosis involving right half of the tongue.
Fig 1. Right common carotid angiogram showed normal lingual artery filling (arrow).
Fig 2. Right common carotid angiogram performed after chemotherapy showed occlusion of the proximal lingual artery (arrow).
necrosis of the tongue after intraarterial chemotherapy has been previously reported. The lingual artery classically arises as the third branch from the external carotid artery. Homze et al.11 found 4 cases in 91 dissections in which the lingual artery arose with the facial artery as a lingual-facial trunk. Our patient, who had advanced buccal cancer, underwent transfemoral catheterization to the external carotid artery just proximal to the orifice of the facial artery, and no lingual-facial trunk was seen (Fig 1). However, the patient believed that the catheter was displaced and also felt a burning sensation in the tongue during the infusion of cisplatin just a few hours after initial catheterization. Before removal of the catheter, he received a total intraarterial infusion of 3300 mg 5-FU. Perhaps the tip of the catheter became dislodged into the lingual artery after catheterization. It is possible that the catheter caused spasm of the lingual artery as Lee et al.10 described on angiogram or embolization developed after dislodgment of the catheter. In addition to the catheter-related complications, cisplatin-based chemotherapy may have resulted in major arterial occlusion12 and autonomic neuropathy with potentiation of arterial spasm.13 5-FU can also cause arterial endothelial wall damage.14 These factors may have played a role in embarrassing the blood supply to the tongue. Although the tongue receives its blood supply from both lingual arteries, there is no marked anastomosis between the lingual arteries except at the tip and base of the tongue and the submucosal surface.15 Intraarterial chemotherapy is an alternative treatment for advanced head and neck cancer. However, it is invasive, and the long-term indwelling catheter should be carefully anchored. Although the procedure has been developed for more than 40 years, it still possesses certain morbidity and mortality. The treating physician should be aware of the position of the catheter tip and condition of patient during the course of treatment to prevent severe and irreversible complications. When dislodgment of the catheter is noted, chemotherapy should be stopped and the catheter withdrawn immediately.
Otolaryngology– Head and Neck Surgery Volume 121 Number 5
REFERENCES 1. Pendás SL, De Vicente Rodríguez JC, González García M, et al. Tongue necrosis as a complication of temporal arteritis. Oral Surg Oral Med Oral Pathol 1994;78:448-51. 2. Park SS, Karp DD, Karmody CS. Lingual necrosis as the initial symptom of small cell carcinoma. Otolaryngol Head Neck Surg 1995;112:782-4. 3. Gault DT. Tongue necrosis after radical neck dissection. Head Neck Surg 1988;10:344-5. 4. Ekman-Joelsson BM, Kjellman B, Hattevig G. Tongue necrosis due to vasculitis. Acta Paediatr 1995;84:1333-6. 5. Korn S, Huppert A, Spitzer S, et al. Systemic lupus erythematosus presenting with lingual infarction. J Rheumatol 1988;15: 1281-3. 6. Klopp CT, Alford TC, Bateman J, et al. Fractionated intraarterial cancer chemotherapy with methyl bis amine hydrochloride: a preliminary report. Ann Surg 1950;132:811-32. 7. Wheeler RH, Ziessman HA, Medvec BR, et al. Tumor blood flow and systemic shunting in patients receiving intraarterial chemotherapy for head and neck cancer. Cancer Res 1986;46:4200-4. 8. Donegan WL. Regional infusion chemotherapy for cancer of the head and neck. Surgery Annual 1975;7:137-73.
657
9. Cheung DK, Regan J, Savin M, et al. A pilot study of intraarterial chemotherapy with cisplatin in locally advanced head and neck cancer. Cancer 1988;61:903-8. 10. Lee YY, Dimery IW, Tassel PV, et al. Superselective intra-arterial chemotherapy of advanced paranasal sinus tumors. Arch Otolaryngol Head Neck Surg 1989;115:503-11. 11. Homze EJ, Harn SD, Bavitz BJ. Extraoral ligation of the lingual artery, an anatomic study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997;83:321-4. 12. Doll DC, List AF, Greco FA, et al. Acute vascular ischemic events after cisplatin-based combination chemotherapy for germ-cell tumors of the testis. Ann Intern Med 1986;105:4851. 13. Rosenfeld CS, Broder LE. Cisplatin-induced autonomic neuropathy. Cancer Treatment Reports 1984;68:659-60. 14. Cwikiel M, Zhang B, Eskilsson J, et al. The influence of 5-fluorouracil on the endothelium in small arteries. An electron microscopic study in rabbits. Scanning Microsc 1995;9:56176. 15. Zimmerman RA, McLean G, Freiman D, et al. The diagnostic and therapeutic role of angiography in lingual arterial bleeding. Radiology 1979;133:639-43.