- Email: [email protected]
Predisposing factors, management, and prognostic evaluation of acute carotid blowout syndrome
Predisposing factors, management, and prognostic evaluation of acute carotid blowout syndrome Hsueh-Ju Lu, MD,a,d,f Kuo-Wei Chen, MD,a,d Ming-Huang Chen, MD,a,d Pen-Yuan Chu, MD,b,d Shyh-Kuan Tai, MD,b,d Ling-Wei Wang, MD,c,d Peter Mu-Hsin Chang, MD,a,d and Muh-Hwa Yang, MD, PhD,a,e Taipei and Changhua, Taiwan Background: Massive hemorrhages occur in 6%-10% of patients with advanced cancer. Acute carotid blowout syndrome is the most severe massive hemorrhagic complication in head and neck cancer patients. Methods: This was a single institute, retrospective, case control study. A total of 45 patients were enrolled in this study. The predisposing factors, management, and prognosis of acute carotid blowout syndrome were evaluated. Results: Among the baseline characteristics, the site of the primary tumor (P [ .003), origin of bleeding (P [ .048), method of intervention (P [ .005), and time to intervention (P [ .006) were significantly different factors between survivor and nonsurvivor patients. After 24 hours of onset, a Glasgow Coma Scale score (P [ .000), the use of inotropic agents (P [ .007), and neutrophil-to-lymphocyte ratio (P [ .019) were significantly predicting factors for outcome. Multivariate logistic regression analyses revealed bleeding from common carotid artery was an independent factor for long-term survival (odds ratio, 25.951; 95% confidence interval [CI], 1.373-490.441; P < .030). The median overall survival of survivors and nonsurvivors were 12.1 (range, 3.7-118.7; 95% CI, 4.33-54.87) and 11.9 (range, 0.7-53.5; 95% CI, 5.78-25.69) months, respectively (P [ .092). Conclusions: Early and aggressive intervention is important for the successful management of acute carotid blowout syndrome. The Glasgow Coma Scale score, the use of inotropic agents, and neutrophil-to-lymphocyte ratio 24 hours after the onset were predictive factors for patients’ outcomes. Bleeding from common carotid artery is an independent prognostic factor in multivariate analysis. Long-term survival can be achieved after successful management. (J Vasc Surg 2013;58:1226-35.)
Massive hemorrhages occur in approximately 6%-10% of patients with advanced head and neck cancer (HNC). These events may result from local vessel damage caused by direct tumor invasion or from systemic processes such as intravascular coagulopathy or abnormalities in platelet function and number.1 Acute catastrophic bleeding leads to the rapid demise of the patient, and uncontrolled bleeding can be quite distressing for staff, patients, and families.2 Therefore, sufficient preparation for both the medical and psychological aspects of these bleeding events is important.3 Because of heterogeneous etiology of bleeding events, the first step in management is to identify the underlying cause. On the other hand, optimal strategies
From the Division of Hematology and Oncology, Department of Medicine,a Department of Otolaryngology,b and Cancer Center,c Taipei Veterans General Hospital; the Faculty of Medicine,d and Institute of Clinical Medicine,e National Yang Ming University, Taipei; and the Department of Medicine, Show Chwan Memorial Hospital, Changhua.f This study was supported by grants from Taipei Veterans General Hospital (V102A-003) and Taiwan Cancer Clinic Research Foundation. Author conflict of interest: none. Reprint requests: Muh-Hwa Yang, MD, PhD, and Peter Mu-Hsin Chang, MD, Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Rd, Taipei, Taiwan 112, ROC (e-mail: [email protected]). The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest. 0741-5214/$36.00 Crown Copyright Ó 2013 Published by Elsevier Inc. on behalf of the Society for Vascular Surgery. All rights reserved. http://dx.doi.org/10.1016/j.jvs.2013.04.056
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for controlling acute life-threatening bleeding and late complications that may influence the prognosis for overall survival (OS) should also be evaluated.1 Acute carotid blowout syndrome (ACBS) is one of the most complex bleeding complications that may occur in HNC patients. Carotid blowout syndrome (CBS) has been categorized as threatened, impending, and acute subtypes defined as different severity of an episode of hemorrhage or exposure of a portion of the carotid arterial system, which frequently occurs in patients with radiation-induced necrosis, recurrent tumors, wound complications, or pharyngocutaneous fistula.4 Threatened CBS means a visible exposed carotid artery without healthy tissue covered. The rupture will happen after a period of time. The secondary type is impending CBS. These patients have a short-lived acute hemorrhage and resolved either spontaneously or with simple packing. It is considered that sentinel hemorrhages happen from a ruptured vessel with a pseudoaneurysm and the leakage combine with intermittently bleeding. Because there is no real wall with supporting structural elements around the pseudoaneurysm, complete rupture is a certainty and may occur at any time. The third group, defined as ACBS, is an acute profuse hemorrhage, which is not self-limiting and advanced cardiac life support (ACLS) is inevitable.4 For clinicians, the most difficult complication to manage is massive bleeding due to ACBS. In Taiwan, because of the unique lifestyle factor of betel nut chewing,5 the incidence of HNC has increased persistently while the age of the patients has decreased.6 These patients usually have large primary tumors because of this habit, which possibly increases the risk of ACBS.7 The
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identification of strategies for successfully managing ACBS is therefore an important issue. For patients who are successfully treated for ACBS, aggressive resuscitation may be the key. However, the respective mortality and major neurologic morbidity rates of ACBS are 40% and 60%,4,8 respectively. ACBS treatment failure is a major psychological burden for the treating physicians, the patient, and the patient’s family. In addition, the late complications that occurs following aggressive resuscitation decrease the quality of life and eventually the OS of the affected patients.3 Because ACBS is a suffering event for patients and their families, understanding the prognosis and outcome is important for clinics. Therefore, we sought to identify the predisposing factors, effective management strategies, and prognostic factors for ACBS. The results of this study will aid in improving the outcome of patients with the specific complication of massive tumor bleeding. METHODS Study design, setting, and patient selection. The present study was a single institution, retrospective, case control study. It was reviewed and approved by the Institutional Review Board of Taipei Veterans General Hospital (No. 2012-07-034BC). ACBS was defined as acute, profuse hemorrhage that was not self-limiting over the carotid trunk4 or bleeding episodes in which ACLS was necessary. Patients were enrolled between January 1, 2001 and December 31, 2011 according to the imaging and operation records. Because this was a retrospective study, patient selection was performed according to medical records. However, the terms, including tumor bleeding, carotid blowout, oral bleeding, or neck wound bleeding were described as massive bleeding in the medical history charts. For the purpose of identifying the true ACBS cases, only patients with images confirmed by neck computed tomography (CT)/CT angiography (CTA), invasive carotid angiography, or positive operation findings were enrolled. Those diagnosed with CBS without ACLS, and imaging/operation findings were excluded. Successful management of ACBS was defined as survival of the patient after an episode of ACBS longer than 72 hours. Those who survived for less than 72 hours were classified as the nonsurvivor group. Because the presence and persistence of acute circulatory failure in patients with shock is recognized to be a poor prognostic indication, and resolution of shock in survivors usually occurs within the first 72 hours,9 early resolution of shock in such patients might be associated with improved outcomes. Several large prospective randomized studies also use a duration of 72 hours as a successful end point for patients treated with acute shock.10,11 Therefore, we divided patients with or without survival after an acute episode according to patients who did or did not survive longer than 72 hours. Basic demographic data were recorded, including age, sex, and initial presentation of the primary tumor (eg,
Lu et al 1227
tumor site, staging, pathologic type, preventive therapy for ACBS, and local recurrence before ACBS). The descriptions of the bleeding (eg, origin, left or right side, intra- or extra-oral, and cause of bleeding), and the managements at the onset of ACBS were also collected. Management of ACBS. During the onset, ACLS was performed first. Protection of the airway with oral intubation or tracheotomy was also included if necessary. Restoration of circulating volume was achieved initially by rapid fluid infusion through large-bore peripheral cannulae. Direct compression of the bleeding source with epinephrine packing was performed on all patients. Inotropic agents were administered to the patients if they had persistent shock status (systolic blood pressure <90 mm Hg or diastolic blood pressure <60 mm Hg) without improvement after massive fluid challenge. At our institution, at least one interventional neuroradiologist or cardiovascular surgeon was available within 30 minutes.12 For patients with ACBS, emergent endovascular treatment or surgical ligation, which was the procedure immediately at the time of ACBS onset, was done to reduce the blood loss. For patients without ACBS, selective endovascular treatment was also arranged to prevent an unexpected rupture.4 Critical care in the intensive care unit and inotropic agent use were implemented according to the condition of the patients and the clinicians’ evaluations. The best supportive care was defined as patients that excluded emergent endovascular treatment or surgical ligation. Other aggressive treatments according to clinical conditions, such as fluid hydration, inotropic agents, blood transfusion, and ACLS were still administered. Outcome evaluation. The Glasgow Coma Scale score was evaluated every 4 hours. The complications were recorded according to whether they occurred in the acute or delayed time frame. Acute complications were defined as those that occurred within 72 hours of the onset of ACBS, and those that occurred more than 72 hours after the onset of ACBS were considered as delayed complications. The neutrophil-to-lymphocyte (N/L) ratio differences, which indicate the severity of clinical physiological stress,13,14 were also recorded before and 24 hours after ACBS onset. To understand the influence of ACBS to the long-term survival of HNC, OSs were analyzed for survivors and nonsurvivors. OS was calculated from the date of disease diagnosis to the date of death by any cause, or the date on which the patient was last evaluated. Statistical analysis. Categorical variables were compared using the c2 and Fisher exact tests. The Mann-Whitney test was used for continuous variables. The independent factors of surviving longer than 72 hours were analyzed with univariate and multivariate logistic regressions. We used logistic regression to analyze the risk factors for survival because the end point of univariate and multivariate analysis was to predict survival or not after ACBS rather than the impact of ACBS for survival duration. The factors with P value of <.05 in univariate analyses were included in multivariate logistic regressions. OS was analyzed using the log-rank test and expressed as Kaplan-Meier plots.
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A value of P < .05 was considered statistically significant. All statistical analysis was performed using SPSS statistical software v. 18.0 (SPSS Inc, Chicago, Ill). RESULTS Baseline characteristics between survivor and nonsurvivor patients. Between January 1, 2001 and December 31, 2011, there were 3504 patients with newly diagnosed HNC in our institution. One hundred and three patients (103/3504, 2.9%) who suffered from CBS were identified by imaging/operation finding. They included threatened, impending, and acute subtypes of CBS based on the study by Chaloupka et al.4 Among these, only 45 patients with ACBS, which included acute and profuse hemorrhage without self-limiting over the carotid trunk and immediately emergent treatments where necessary, were enrolled in the present study to analyze the predisposing factors, management, and prognosis. Thirty-four patients (34/45, 75.6%) were treated successfully after aggressive management, whereas 11 patients were treated unsuccessfully. Other patients without ACBS and who accepted preventive or scheduled therapies have been analyzed in our previous study.15 Basic characteristics of both survivor and nonsurvivor patients are presented in Table I. Nearly one-half of patients (19/45, 42.2%) were younger than 50 years old and 91.1% of patients (41/45) were male. Squamous cell carcinoma was the most common pathologic type (38/ 45, 84.4%). There were significant differences between the two groups in tumor site (P ¼ .003), origin of bleeding (P ¼ .048), method of intervention (P ¼ .005), and time to intervention (P ¼ .006). The longest time to intervention of those ACBS patients with invasive procedures was 49 hours. Because there were eight patients who refused any invasive treatments and the time to intervention would be infinite for them, we recorded these cases as up to 60 hours to represent the longest time to intervention. The median times to intervention for both groups were 3.3 hours (0.4-60.0) and 60.0 hours (1.5-60.0), respectively. The survivor patients had a significantly shorter time to intervention than nonsurvivor patients (P ¼ .003). Other factors such as aggressive hydration, intensive critical care, and blood component support were similar (Table I). Angiography resulted in more precise diagnosis of ACBS bleeding site than computed tomography. Fig 1 shows two cases of successful ACBS treatment. A 54-yearold man who was diagnosed with hypopharyngeal cancer had ACBS (Fig 1, A and B). This patient was under palliative chemotherapy because of recurrent disease. The CT scan revealed necrotic soft tissue involving the retropharyngeal region (Fig 1, A). The angiography examination revealed acute extravasation from a pseudoaneurysm of the left middle common carotid artery (CCA) (Fig 1, B). After aggressive management, this patient survived for 7 months from the time of onset. The second case (Fig 1, C and D) involved a 67-year-old man who was diagnosed with glottic cancer and admitted because of poor wound
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healing after neck dissection. The CT scan showed a deep ulcerative wound that was close to the right CCA in the right anterior neck (Fig 1, C). The lesion that was present in the right CCA is shown in Fig 1, D. After emergent endovascular treatment, the patient survived and was followed in the clinical ward for more than 16 months. Univariate and multivariate logistic regression analysis for prognostic factor of ACBS. Univariate analyses of survivor patients also revealed that primary tumor site (oropharynx, P ¼ .006; hypopharynx, P ¼ .048), the origin of bleeding (CCA, P ¼ .031), method of intervention (best supportive care, P ¼ .002), and time to intervention (>12 hours, P ¼ .020) were significant prognostic factors. Multivariate analyses indicated that bleeding of the CCA was the only independent factor for survivor patients (odds ratio, 25.951; 95% confidence interval [CI], 1.373490.441; P < .030) (Table II). Because of the small number of patients enrolled in this study, the characteristics of ACBS patients were unevenly distributed. Such distribution pattern resulted in the large range of 95% CI. Consciousness level, the use of inotropic agents, and N/L ratio change are important predictors for the outcomes of ACBS. Under aggressive treatment, the incidence of acute complications was similar in both groups. Aspiration pneumonia and stroke/transient ischemic attack were the most common complications. More patients in the survivor group had a better consciousness level (Glasgow coma score $9) than patients in the nonsurvivor group 24 hours after ACBS onset (P ¼ .000; Table III). Inotropic agent used 24 hours after ACBS was significantly higher in nonsurvivor patients (P ¼ .007). The hemoglobin concentration was recorded to evaluate the hemodynamic status of the patients, which did not differ between the two groups. Because the N/L ratio reflects the level of severe physiological stressors such as massive bleeding or critical condition,13-17 the baseline and 24-hour N/L ratios were assessed. There were similar N/L ratios between the groups at the onset of ACBS (P ¼ .605); however, both groups had a higher N/L ratio than the baseline 24 hours after onset (P ¼ .019 and .012; Fig 2). The N/L ratio 24 hours after onset was higher in the nonsurvivor group compared with the survivor group (P ¼ .007; Table III; Fig 2). Outcomes of the various treatment modalities. Except eight patients without aggressively invasive treatment, there were 30 patients who received endovascular therapy and seven patients received surgical treatment. Patients would receive surgical ligation if radical neck dissection was done recently without the wound healing completely. The most frequent etiology of bleeding after radical neck dissection was tumor involvement (4/7; 57.1%). Others included fistula formation (1/7; 14.3%), local inflammation/necrosis (1/7; 14.3%), and postoperation complication (1/7; 14.3%). Surgical treatment showed a higher mortality rate than endovascular therapy. Mortality rate of best supportive care, endovascular therapy, and surgical ligation were 75% (6/8), 10% (3/30), and 28.6% (2/7), respectively.
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Table I. Continued.
Table I. Basic characteristics of patients with ACBS
Characteristics Age, years $50 <50 Sex Male Female Tumor site Oral cavity Nasopharynx Oropharynx Hypopharynx Larynx Othersa Initial T stage #T2 >T2 Unknownb Initial N stage N0 Nþ Unknownb Initial M stage M0 M1 Pathologic type Squamous cell carcinoma Adenosquamous carcinoma Nonkeratinizing carcinoma Leiomyosarcoma Carcinoma, undifferentiated Prevent therapy for ACBS None Stent insertion Embolization Stent insertion and embolization Surgical procedure Local recurrence before ACBS Yes No Origin of bleeding ICA ECA or its branches CCA Carotid bifurcation Combinationc Unknownd Side of ACBS Left Right Site of bleeding Intraoral Extraoral Cause of bleeding Tumor relatede Pseudoaneurysm Soft tissue inflammation Fistula formation Postoperative complication Method of intervention Best supportive care Stent insertion Embolization
Survivor patients (n ¼ 34)
Nonsurvivor patients P (n ¼ 11) value .273
21 (61.8%) 13 (38.2%)
5 (45.5%) 6 (54.5%) .311
30 (88.2%) 11 (100.0%) 4 (11.8%) 0 (0.0%) .003 8 2 4 16 1 3
(23.5%) (5.9%) (11.8%) (47.1%) (2.9%) (8.8%)
0 2 6 1 2 0
(0.0%) (18.2%) (54.5%) (9.1%) (18.2%) (0.0%) .520
9 (26.5%) 24 (70.6%) 1 (2.9%)
4 (36.4%) 6 (54.5%) 1 (9.1%) .141
6 (17.6%) 26 (76.5%) 2 (5.9%)
5 (45.5%) 5 (45.5%) 1 (9.1%) .422
31 (91.2%) 11 (100.0%) 3 (8.8%) 0 (0.0%) .207 30 1 1 1 1
(88.2%) (2.9%) (2.9%) (2.9%) (2.9%)
8 0 2 0 1
(72.7%) (0.0%) (18.2%) (0.0%) (9.1%)
28 0 2 2
(82.4%) (0.0%) (5.9%) (5.9%)
9 1 1 0
(81.8%) (9.1%) (9.1%) (0.0%)
.341
2 (5.9%)
0 (0.0%)
20 (58.8%) 14 (41.2%)
8 (72.7%) 3 (27.3%)
5 16 7 4 1 1
0 2 5 1 0 3
.325
Characteristics
Survivor patients (n ¼ 34)
Stent insertion and 4 (11.8%) embolization Surgical procedure 5 (14.7%) Time to intervention, hours #3 15 (44.1%) >3 and #6 7 (20.6%) >6 and #12 4 (11.8%) >12 6 (17.6%) Patients refuse 2 (5.9%) Total fluid challenge in the first 24 hours, L #2 1 (4.2%) >2 and #3 5 (20.8%) >3 and #4 4 (16.7%) >4 14 (58.3%) No. of patients available 24 Total fluid output in the first 24 hours, L #2 9 (37.5%) >2 and #3 7 (29.2%) >3 and #4 3 (12.5%) >4 5 (20.8%) No. of patients available 24 The blood component support in the first 24 hours, U PRBC 4 (0-28) Plt. pheresis 0 (0-4) FFP 2 (2-16) Intensive critical care 20 (58.8%)
Nonsurvivor patients P (n ¼ 11) value 0 (0.0%) 2 (18.2%) .006 1 2 1 1 6
(9.1%) (18.2%) (9.1%) (9.1%) (54.5%) .667
0 3 1 3
(0.0%) (42.9%) (14.3%) (42.9%) 7 .188
3 0 3 1
(42.9%) (0.0%) (42.9%) (14.3%) 7
4 0 4 5
(4-16) (0-4) (4-14) (45.5%)
.369 .429 .387 .333
ACBS, Acute carotid blowout syndrome; CCA, common carotid artery; ECA, external carotid artery; ICA, internal carotid artery; FFP, fresh frozen plasma; Plt, platelet; PRBC, packed red blood cells. a Others: carcinoma of unknown primary, nasal antrum, and ethmoid sinus cancer. b Unknown cases were diagnosed at another hospital without initial data. c The origins of bleeding involved left ICA, lingular artery and superior thyroid arteries. d Patients and their families refused invasive procedures at ACBS onset. e Including tumor necrosis or tumors involving the vessels.
.048 (14.7%) (47.1%) (20.6%) (11.8%) (2.9%) (2.9%)
(0.0%) (18.2%) (45.5%) (9.1%) (0.0%) (27.3%) .466
18 (52.9%) 16 (47.1%)
5 (45.5%) 6 (54.5%)
21 (61.8%) 13 (38.2%)
8 (72.7%) 3 (27.3%)
13 15 3 2 1
7 3 0 1 0
.390 .522 (38.2%) (44.1%) (8.8%) (5.9%) (2.9%)
(63.6%) (27.3%) (0.0%) (9.1%) (0.0%) .005
2 (5.9%) 3 (8.8%) 20 (58.8%)
6 (54.5%) 0 (0.0%) 3 (27.3%)
The detailed results are shown in Table I. Because the number of patients was too small in each treatment group, the modalities were hard to compare with each other. For patients who received embolization and surgical ligation, the most frequent complication was aspiration pneumonia (14/23, 60.9% for embolization; 3/7, 42.9% for surgical ligation). Delayed stroke/transient ischemic attack was the main problem of patients with stent insertion (1/3, 33.3%). Recurrent CBS treated with endovascular therapy and surgical ligation were 20% (6/30) and 0% (0/7), respectively. Long-term survival of patients after successful management of ACBS. To understand the influence of ACBS on the disease course, Kaplan-Meier analyses were used to evaluate the long-term survival trends. The median overall survival of survivors and nonsurvivors were 12.1 (range, 3.7-118.7; 95% CI, 4.33-54.87) and 11.9 (range, 0.7-53.5; 95% CI, 5.78-25.69) months, respectively (P ¼ .092) (Fig 3).
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Fig 1. Computed tomography (CT) and angiography findings of acute carotid blowout syndrome (ACBS). In (A) and (B), a 54-year-old man who was diagnosed with hypopharyngeal cancer and under palliative chemotherapy treatment presented with acute left common carotid artery (CCA) CBS. A CT scan revealed necrotic soft tissue involving the left CCA (thick black arrow). The angiography results revealed acute extravasation from a pseudoaneurysm of the left middle CCA (thick white arrow). In (C) and (D), a 67-year-old man with glottic cancer was evaluated for poor wound healing following neck dissection. A deep ulcerative wound was found in the right anterior neck. The lesion was close to the right CCA (thin black arrow). Acute rupture in the right CCA was found on angiography (thin white arrow).
DISCUSSION ACBS, usually a life-threatening complication of HNC, is accompanied with unexpectedly massive bleeding and high mortality/morbidity rates.4,8 In this study, location of primary tumor and bleeding sites, as well as early and aggressive interventions persistently showed importance for survivor patients. The changes in the consciousness level, inotropic agent usage, and N/L ratio after 24 hours were the major factors that were predictive of ACBS outcomes. Multivariate analysis showed that CCA bleeding was the significantly prognostic factor for long-term survival. Surgical ligation and endovascular therapy are the main treatments for CBS patients. Surgical management was the first option for CBS patients traditionally.18 Because ACBS was an early complication following radical neck dissection, some patients would receive surgical ligation if radical neck dissection was done recently without the wound healing completely.18,19 Raising skin flaps in the neck was quick and easy to expose deep cervical fascia and to check bleeding, this procedure was also the emergent method to stop bleeding. After removing skin flaps, deep cervical fascia and carotid sheath, which coated internal jugular vein, vagus nerve, and carotid artery, were dissected. After
identifying the source of bleeding, the rupture site was repaired, and the carotid artery was ligated. If the border of the artery or other vital organs could not be divided clearly because of severe fibrosis, we would keep finding carotid artery through the pulsation. Then, the CCA and the furcation area could be reached. Debridement was also done if necrotic tissue was found. The operative wound was irrigated with beta-iodine and normal saline to minimize the contamination. Then, the wound was closed with Vicryl and nylon. After completing the procedure, patients were sent to the intensive care unit for postoperative care. However, open surgical techniques were gradually replaced with endovascular therapy because of high mortality/morbidity after surgical ligation.18,20 In addition, direct exploration and repair of the previously irradiated field were also difficult for surgeons to approach.19 Therefore, endovascular therapy, including destructive (embolization) and constructive (stent grafting) techniques, are gaining popularity for the treatment of ACBS recently. More and more articles have discussed the effect and outcomes of endovascular therapy.19,20 The morbidity/mortality rates are significantly decreased in endovascular therapy than in surgical treatment.20,21
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Table II. Univariate and multivariate logistic regression analysis for the prognostic factor of ACBS Multivariate Variable Age, $50 years Male Tumor site Oral cavity Nasopharynx Oropharynx Hypopharynx Larynx Pathological type Squamous cell carcinoma Adenosquamous carcinoma Nonkeratinizing carcinoma Leiomyosarcoma Carcinoma, undifferentiated Prevent therapy for ACBS Treatment just before ACBS Palliative chemotherapy Concurrent chemoradiotherapy None Origin of bleeding ICA ECA or its branches CCA Carotid bifurcation Combinationa Cause of bleeding Tumor relatedb Pseudoaneurysm Soft tissue inflammation Fistula formation Postoperative complication Method of intervention Best supportive care Stent insertion Embolization Stent insertion and embolization Surgical procedure Time to intervention, hours #3 >3 and #6 >6 and #12 >12 Local recurrence before ACBS
Univariate P value
P value
OR (95% CI)
.229 .099
5.369 (0.347-83.090) 0.056 (0.002-1.717)
.030
25.951 (1.373-490.441)
.394
4.759 (0.132-171.649)
.783
1.494 (0.086-25.981)
.345 .999 .999 .235 .006 .048 .120 .230 1.000 .120 1.000 .413 .968 .243 .999 .433 .999 .242 .031 .977 1.000 .149 .327 .999 .713 1.000 .002 .999 .079 .999 .783 .061 .862 .807 .020 .412
ACBS, Acute carotid blowout syndrome; CCA, common carotid artery; CI, confidence interval; ECA, external carotid artery; ICA, internal carotid artery; OR, odds ratio. a The origins of bleeding involved left ICA, lingular artery, and superior thyroid arteries. b Including tumor necrosis or tumors involving the vessels.
There are two kinds of endovascular therapies, including deconstructive and constructive. However, there were limited data that compare the outcomes between deconstructive and constructive treatments for patients with ACBS.20 Current evidence shows that there was no significant difference in technical and hemostatic outcomes between the reconstructive and deconstructive endovascular methods19-21 because permanent vessel occlusion resulted in higher immediately cerebral ischemia and stent grafting induced the more potentially delayed complications, such as infection, rebleeding, and stent thrombosis.18,20 In our practice, patients whose pathologic
lesions involved the branches of external carotid artery were only administered with deconstructive management.19 Those involving the main trunk of the carotid artery received either deconstructive treatment or constructive treatment according to the result of a balloon occlusion test (BTO), which evaluates blood supply from intracranial collateral circulation.22 Stent grafting was considered if the circle of Willis was incomplete, or an unstable clinical condition precluded BTO. Because stent grafts have to be self-paid by patients in Taiwan, the cost effectiveness should also be explained. Stent grafting was also suggested if the areas of pathologic involvement
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Table III. Outcome characteristics of patients with ACBS Variable Glasgow coma score after 24 hours $9 6-8 #5 Unknown Inotropic agent use 24 hours after ACBS No. of patients evaluated Acute complicationsa Stroke/TIA Aspiration pneumonia Femoral hematoma Delayed complicationsa Stroke/TIA Aspiration pneumonia Brain abscess Wound infection Empyema Femoral hematoma Upper gastrointestinal bleeding due to antiplatelet agents Serum markers 24 hours after ACBS onset Complete blood count WBC (103 cells/mL) >10.0 Hgb (g/dL) <11.0 PLT (103 cells/mL) >400.0 No. of patients evaluated Differential count N/L ratio Monocyte (cells/mL) >1000 No. of patients evaluated
Survivor patients (n ¼ 34)
Nonsurvivor patients (n ¼ 11)
P value .000
29 2 4 3 11
(73.5%) (5.9%) (11.8%) (8.8%) (32.4%) 34
3 (8.8%) 13 (38.2%) 1 (2.9%)
0 3 6 2 7
(0.0%) (27.3%) (54.5%) (18.2%) (87.5%) 8
.007
0 (0.0%) 4 (36.4%) 0 (0.0%)
.422 .602 .756
NA NA NA NA NA NA NA
NA NA NA NA NA NA NA
19 (63.3%) 5 (16.7%) 1 (3.3%) 30
7 (100%) 3 (42.9%) 1 (14.3%) 7
.064 .156 .347
20.7 (5.9-48.5) 10 (35.7%) 28
48.5 (10.5-93.0) 3 (42.9%) 7
.007 .525
2 4 1 2 1 1 2
(5.9%) (11.8%) (2.9%) (5.9%) (2.9%) (2.9%) (5.9%)
ACBS, Acute carotid blowout syndrome; Hgb, hemoglobin; NA, not analyzed; N/L, neutrophil-to-lymphocyte; PLT, platelet count; TIA, transient ischemic attack; WBC, white blood cell. a Acute complications were defined as complications that occurred within 72 hours after massive bleeding; delayed complications were defined as those that occurred after more than 72 hours.
were too large to be embolized, so that embolizing to the external carotid artery or its branches and keeping the blood supply from CCA to the internal carotid artery (ICA) with stent grafting were considered. There are some reasons that permanent vessel occlusion remains the standard therapy for ACBS patients in our institution. First, because delayed complications and long-term outcomes are unclear with stent grafting,18,20 constructive treatment has to be self-paid by patients in Taiwan and the cost effectiveness of stent grafting should be evaluated. Second, whether the ability of stopping bleeding is comparable in stent grafting is still controversial.15,22,23 So, the constructive treatment was only applied for patients with the incomplete circle of Willis, precluding an occlusion test, or intolerant BTO, that when carotid occlusion poses an unusually high risk of neurologic morbidity.24 Initial resuscitation in a minimal amount of time and identification of the source of bleeding with immediate intervention are critical for the management of massive bleeding events.25 These management strategies result in successful patient survival and hemostasis.19 At our institution, interventional teams were available within 30 minutes after they were informed about a massive bleeding event. Other multidisciplinary teams were also placed on all-day
standby.12 Therefore, at the onset of ACBS, ACLS was provided immediately in accordance with the patients’ needs, and invasive interventions were prepared well in advance. Blood component support and critical care after these interventions were more readily available at our hospital compared with other local medical institutions. With multidisciplinary cooperation, we were able to provide a high level of medical care for all patients with ACBS and achieved a good success rate. The primary tumor site and origin of bleeding significantly influenced the patient outcomes. In a previous study, the luminal vessel diameter impacted the outcome of ACBS, as it is relatively difficult to perform interventions and control hemostasis in vessels with large luminal diameters.26 Moreover, patients with ICA or CCA involvement are more likely to experience immediate/delayed cerebral ischemia and more blood loss,24 which leads to high mortality/morbidity rates. Another possible explanation is that a primary tumor that is located far from the ICA or CCA is less likely to directly involve these arteries, which also results in better survival outcomes. ACBS is a rare and rapidly progressive complication. ACBS patients always suffer from loss of consciousness, cardiac arrest, or hypovolemic shock; ACLS is needed at
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Fig 2. Neutrophil-to-lymphocyte (N/L) ratio before and after acute carotid blowout syndrome (ACBS) in survivor or nonsurvivor patients. The N/L ratios were significantly higher 24 hours after ACBS onset relative to those at initial onset (P ¼ .012 and .019 in both groups, respectively). The N/L ratio did not differ between both groups at initial onset (P ¼ .527), but was significantly much higher in the group with nonsurvivors than in the group with survivors after 24 hours (P ¼ .007).
the time of onset. Because of a critical complication and difficulty to manage, patients may expire in a very short period of time without enough follow-up. Hemodynamic status is an important factor that is capable of predicting the outcome of massive bleeding because it results in prolonged hypovolemic shock and severe vasoconstriction. This condition also induces multiorgan failure and tissue ischemia.25,27 However, it is difficult to evaluate hemodynamic status using blood pressure measurements and the volume of blood transfused in practice, as vessel constriction and the use of inotropic agents might mask the real hemodynamic status. Some articles have proposed the prognostic factors to evaluate patients with severe shock, but they were inappropriate for ACBS patients because of short clinical courses to be followed up.28-34 The use of N/L ratio is easily assessed, and the data are quickly available. Therefore, we examined several serum markers that could reflect the severity of systemic inflammation and physiological stress.13,14 Zahorec et al used the N/L ratio as a parameter for the intensity of stress/systemic inflammation in critically ill patients following shock, multiple trauma, major surgery, or sepsis.13 Physiological stress is reflected as systemic inflammation,35 which mediates complex interactions that influence the N/L ratio.14 Therefore, in patients who have systemic stress/inflammation and local endothelial injury, the N/L ratio indeed reflects the degree of endovascular injury and disease
Lu et al 1233
Fig 3. Overall survival of survivors and nonsurvivors. The median overall length of survival of survivors and nonsurvivors was 12.1 (range, 3.7-118.7; 95% confidence interval [CI], 4.33-54.87) and 11.9 (range, 0.7-53.5; 95% CI, 5.78-25.69) months, respectively (P ¼ .092).
severity.16,17 The results of the current study also suggested that patients who did not survive had higher levels of physiological stress reflected by an increase in the N/L ratio. In previous studies, the most common cause of mortality for patients that survived ACBS is disease progression rather than related complications.12,26 Our study also showed that the long-term progression-free survival and OS of ACBS patients were similar to those of patients without ACBS.36,37 With successful treatment, long-term survival can be achieved in patients with ACBS. There were some limitations in this study. The first was the small number of patients and inherent selection bias. Because this was a retrospective study, patient selection was performed according to medical records. However, the terms, including tumor bleeding, carotid blowout, oral bleeding, or neck wound bleeding, were described as massive bleeding in the charts. Therefore, it was difficult to identify the true ACBS cases. In our study, in addition to massive bleeding, ACBS was identified according to CT/CTA, invasive carotid angiography, or operation findings. Patients who were diagnosed with bleeding without CT/CTA, invasive carotid angiography, or operation findings were excluded from the analysis. In conclusion, aggressive and early interventions are important for the management of ACBS. Other factors such as the source of bleeding and N/L ratio changes
1234 Lu et al
were prognostic factors for patient outcomes. Bleeding from CCA is an independent prognostic factor. With successful management, long-term survival rates of these patients could be achieved that are comparable with HNC patients without ACBS. The authors thank Miss Ling-Chen Tai in statistical consultation.
AUTHOR CONTRIBUTIONS Conception and design: KC, MC, PC, ST, LW, PC, MY Analysis and interpretation: HL Data collection: HL Writing the article: HL Critical revision of the article: PC, MY Final approval of the article: PC, MY Statistical analysis: HL Obtained funding: Not applicable Overall responsibility: PC, MY
REFERENCES 1. Pereira J, Phan T. Management of bleeding in patients with advanced cancer. Oncologist 2004;9:561-70. 2. Prommer E. Management of bleeding in the terminally ill patient. Hematology 2005;10:167-75. 3. Nauck F, Alt-Epping B. Crises in palliative careea comprehensive approach. Lancet Oncol 2008;9:1086-91. 4. Chaloupka JC, Putman CM, Citardi MJ, Ross DA, Sasaki CT. Endovascular therapy for the carotid blowout syndrome in head and neck surgical patients: diagnostic and managerial considerations. AJNR Am J Neuroradiol 1996;17:843-52. 5. Chen YJ, Chang JT, Liao CT, Wang HM, Yen TC, Chiu CC, et al. Head and neck cancer in the betel quid chewing area: recent advances in molecular carcinogenesis. Cancer Sci 2008;99:1507-14. 6. Bureau of Health Promotion annual report; 2010, Taiwan. Available at: http://health99.doh.gov.tw/en/. 7. Kakizawa H, Toyota N, Hieda M, Hirai N, Tachikake T, Horiguchi J, et al. Massive hemorrhage from internal carotid artery pseudoaneurysm successfully treated by transcatheter arterial embolization with assessment of regional cerebral oxygenation. Cardiovasc Intervent Radiol 2005;28:495-8. 8. Upile T, Triaridis S, Kirkland P, Archer D, Searle A, Irving C, et al. The management of carotid artery rupture. Eur Arch Otorhinolaryngol 2005;262:555-60. 9. Bone RC, Fisher CJ Jr, Clemmer TP, Slotman GJ, Metz CA, Balk RA. A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock. N Engl J Med 1987;317: 653-8. 10. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345:1368-77. 11. Bakker J, Grover R, McLuckie A, Holzapfel L, Andersson J, Lodato R, et al. Administration of the nitric oxide synthase inhibitor NG-methylL-arginine hydrochloride (546C88) by intravenous infusion for up to 72 hours can promote the resolution of shock in patients with severe sepsis: results of a randomized, double-blind, placebo-controlled multicenter study (study no. 144-002). Crit Care Med 2004;32:1-12. 12. Luo CB, Teng MM, Chang FC, Chang CY. Transarterial embolization of acute external carotid blowout syndrome with profuse oronasal bleeding by N-butyl-cyanoacrylate. Am J Emerg Med 2006;24:702-8. 13. Zahorec R. Ratio of neutrophil to lymphocyte countsdrapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy 2001;102:5-14.
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14. Kantola T, Klintrup K, Vayrynen JP, Vornanen J, Bloigu R, Karhu T, et al. Stage-dependent alterations of the serum cytokine pattern in colorectal carcinoma. Br J Cancer 2012;107:1729-36. 15. Lu HJ, Chen KW, Chen MH, Chu PY, Tai SK, Tzeng CH, et al. Serum albumin is an important prognostic factor for carotid blowout syndrome. Jpn J Clin Oncol 2013;43:532-9. 16. de Jager CP, Wever PC, Gemen EF, Kusters R, van GageldonkLafeber AB, van der Poll T, et al. The neutrophil-lymphocyte count ratio in patients with community-acquired pneumonia. PloS One 2012;7:e46561. 17. Akpek M, Kaya MG, Lam YY, Sahin O, Elcik D, Celik T, et al. Relation of neutrophil/lymphocyte ratio to coronary flow to in-hospital major adverse cardiac events in patients with ST-elevated myocardial infarction undergoing primary coronary intervention. Am J Cardiol 2012;110:621-7. 18. Powitzky R, Vasan N, Krempl G, Medina J. Carotid blowout in patients with head and neck cancer. Ann Otol Rhinol Laryngol 2010;119:476-84. 19. Chang FC, Lirng JF, Luo CB, Wang SJ, Wu HM, Guo WY, et al. Patients with head and neck cancers and associated postirradiated carotid blowout syndrome: endovascular therapeutic methods and outcomes. J Vasc Surg 2008;47:936-45. 20. Shah H, Gemmete JJ, Chaudhary N, Pandey AS, Ansari SA. Acute lifethreatening hemorrhage in patients with head and neck cancer presenting with carotid blowout syndrome: follow-up results after initial hemostasis with covered-stent placement. AJNR Am J Neuroradiol 2011;32:743-7. 21. Lesley WS, Chaloupka JC, Weigele JB, Mangla S, Dogar MA. Preliminary experience with endovascular reconstruction for the management of carotid blowout syndrome. AJNR Am J Neuroradiol 2003;24:975-81. 22. Wan WS, Lai V, Lau HY, Wong YC, Poon WL, Tan CB. Endovascular treatment paradigm of carotid blowout syndrome: review of 8-years experience. Eur J Radiol 2013;82:95-9. 23. Meyers PM, Schumacher HC, Higashida RT, Barnwell SL, Creager MA, Gupta R, et al. Indications for the performance of intracranial endovascular neurointerventional procedures: a scientific statement from the American Heart Association Council on Cardiovascular Radiology and Intervention, Stroke Council, Council on CardioVascular Surgery and Anesthesia, Interdisciplinary Council on Peripheral Vascular Disease, and Interdisciplinary Council on Quality of Care and Outcomes Research. Circulation 2009;119:2235-49. 24. Chang FC, Lirng JF, Luo CB, Guo WY, Teng MM, Tai SK, et al. Carotid blowout syndrome in patients with head-and-neck cancers: reconstructive management by self-expandable stent grafts. AJNR Am J Neuroradiol 2007;28:181-8. 25. Rossaint R, Bouillon B, Cerny V, Coats TJ, Duranteau J, FernandezMondejar E, et al. Management of bleeding following major trauma: an updated european guideline. Crit Care 2010;14:R52. 26. Kim HS, Lee DH, Kim HJ, Kim SJ, Kim W, Kim SY, et al. Lifethreatening common carotid artery blowout: rescue treatment with a newly designed self-expanding covered nitinol stent. Br J Radiol 2006;79:226-31. 27. Landry DW, Oliver JA. The pathogenesis of vasodilatory shock. N Engl J Med 2001;345:588-95. 28. Wu TT, Yuan A, Chen CY, Chen WJ, Luh KT, Kuo SH, et al. Cardiac troponin i levels are a risk factor for mortality and multiple organ failure in noncardiac critically ill patients and have an additive effect to the apache ii score in outcome prediction. Shock 2004;22: 95-101. 29. Kumpers P, Lukasz A, David S, Horn R, Hafer C, FaulhaberWalter R, et al. Excess circulating angiopoietin-2 is a strong predictor of mortality in critically ill medical patients. Crit Care 2008;12:R147. 30. Piton G, Manzon C, Monnet E, Cypriani B, Barbot O, Navellou JC, et al. Plasma citrulline kinetics and prognostic value in critically ill patients. Intensive Care Med 2010;36:702-6. 31. Zuber B, Tran TC, Aegerter P, Grimaldi D, Charpentier J, Guidet B, et al. Impact of case volume on survival of septic shock in patients with malignancies. Crit Care Med 2012;40:55-62.
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32. Scarcello E, Ferrari M, Rossi G, Berchiolli R, Adami D, Romagnani F, et al. A new preoperative predictor of outcome in ruptured abdominal aortic aneurysms: the time before shock (TBS). Ann Vasc Surg 2010;24:315-20. 33. Nakayama A, Morita H, Miyata T, Hoshina K, Nagayama M, Takanashi S, et al. Predictors of mortality after emergency or elective repair of abdominal aortic aneurysm in a Japanese population. Heart Vessels 2012 December 30; [Epublication ahead of print]. 34. Robinson WP, Schanzer A, Li Y, Goodney PP, Nolan BW, Eslami MH, et al. Derivation and validation of a practical risk score for prediction of mortality after open repair of ruptured abdominal aortic aneurysms in a US regional cohort and comparison to existing scoring systems. J Vasc Surg 2013;57:354-61.
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35. Kyrou I, Tsigos C. Stress hormones: physiological stress and regulation of metabolism. Curr Opin Pharmacol 2009;9:787-93. 36. Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 2008;359:1116-27. 37. Lorch JH, Goloubeva O, Haddad RI, Cullen K, Sarlis N, Tishler R, et al. Induction chemotherapy with cisplatin and fluorouracil alone or in combination with docetaxel in locally advanced squamous-cell cancer of the head and neck: long-term results of the TAX 324 randomised phase 3 trial. Lancet Oncol 2011;12:153-9.
Submitted Feb 20, 2013; accepted Apr 23, 2013.
Massive hemorrhages occur in approximately 6%-10% of patients with advanced head and neck cancer (HNC). These events may result from local vessel damage caused by direct tumor invasion or from systemic processes such as intravascular coagulopathy or abnormalities in platelet function and number.1 Acute catastrophic bleeding leads to the rapid demise of the patient, and uncontrolled bleeding can be quite distressing for staff, patients, and families.2 Therefore, sufficient preparation for both the medical and psychological aspects of these bleeding events is important.3 Because of heterogeneous etiology of bleeding events, the first step in management is to identify the underlying cause. On the other hand, optimal strategies
From the Division of Hematology and Oncology, Department of Medicine,a Department of Otolaryngology,b and Cancer Center,c Taipei Veterans General Hospital; the Faculty of Medicine,d and Institute of Clinical Medicine,e National Yang Ming University, Taipei; and the Department of Medicine, Show Chwan Memorial Hospital, Changhua.f This study was supported by grants from Taipei Veterans General Hospital (V102A-003) and Taiwan Cancer Clinic Research Foundation. Author conflict of interest: none. Reprint requests: Muh-Hwa Yang, MD, PhD, and Peter Mu-Hsin Chang, MD, Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Rd, Taipei, Taiwan 112, ROC (e-mail: [email protected]). The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest. 0741-5214/$36.00 Crown Copyright Ó 2013 Published by Elsevier Inc. on behalf of the Society for Vascular Surgery. All rights reserved. http://dx.doi.org/10.1016/j.jvs.2013.04.056
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for controlling acute life-threatening bleeding and late complications that may influence the prognosis for overall survival (OS) should also be evaluated.1 Acute carotid blowout syndrome (ACBS) is one of the most complex bleeding complications that may occur in HNC patients. Carotid blowout syndrome (CBS) has been categorized as threatened, impending, and acute subtypes defined as different severity of an episode of hemorrhage or exposure of a portion of the carotid arterial system, which frequently occurs in patients with radiation-induced necrosis, recurrent tumors, wound complications, or pharyngocutaneous fistula.4 Threatened CBS means a visible exposed carotid artery without healthy tissue covered. The rupture will happen after a period of time. The secondary type is impending CBS. These patients have a short-lived acute hemorrhage and resolved either spontaneously or with simple packing. It is considered that sentinel hemorrhages happen from a ruptured vessel with a pseudoaneurysm and the leakage combine with intermittently bleeding. Because there is no real wall with supporting structural elements around the pseudoaneurysm, complete rupture is a certainty and may occur at any time. The third group, defined as ACBS, is an acute profuse hemorrhage, which is not self-limiting and advanced cardiac life support (ACLS) is inevitable.4 For clinicians, the most difficult complication to manage is massive bleeding due to ACBS. In Taiwan, because of the unique lifestyle factor of betel nut chewing,5 the incidence of HNC has increased persistently while the age of the patients has decreased.6 These patients usually have large primary tumors because of this habit, which possibly increases the risk of ACBS.7 The
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identification of strategies for successfully managing ACBS is therefore an important issue. For patients who are successfully treated for ACBS, aggressive resuscitation may be the key. However, the respective mortality and major neurologic morbidity rates of ACBS are 40% and 60%,4,8 respectively. ACBS treatment failure is a major psychological burden for the treating physicians, the patient, and the patient’s family. In addition, the late complications that occurs following aggressive resuscitation decrease the quality of life and eventually the OS of the affected patients.3 Because ACBS is a suffering event for patients and their families, understanding the prognosis and outcome is important for clinics. Therefore, we sought to identify the predisposing factors, effective management strategies, and prognostic factors for ACBS. The results of this study will aid in improving the outcome of patients with the specific complication of massive tumor bleeding. METHODS Study design, setting, and patient selection. The present study was a single institution, retrospective, case control study. It was reviewed and approved by the Institutional Review Board of Taipei Veterans General Hospital (No. 2012-07-034BC). ACBS was defined as acute, profuse hemorrhage that was not self-limiting over the carotid trunk4 or bleeding episodes in which ACLS was necessary. Patients were enrolled between January 1, 2001 and December 31, 2011 according to the imaging and operation records. Because this was a retrospective study, patient selection was performed according to medical records. However, the terms, including tumor bleeding, carotid blowout, oral bleeding, or neck wound bleeding were described as massive bleeding in the medical history charts. For the purpose of identifying the true ACBS cases, only patients with images confirmed by neck computed tomography (CT)/CT angiography (CTA), invasive carotid angiography, or positive operation findings were enrolled. Those diagnosed with CBS without ACLS, and imaging/operation findings were excluded. Successful management of ACBS was defined as survival of the patient after an episode of ACBS longer than 72 hours. Those who survived for less than 72 hours were classified as the nonsurvivor group. Because the presence and persistence of acute circulatory failure in patients with shock is recognized to be a poor prognostic indication, and resolution of shock in survivors usually occurs within the first 72 hours,9 early resolution of shock in such patients might be associated with improved outcomes. Several large prospective randomized studies also use a duration of 72 hours as a successful end point for patients treated with acute shock.10,11 Therefore, we divided patients with or without survival after an acute episode according to patients who did or did not survive longer than 72 hours. Basic demographic data were recorded, including age, sex, and initial presentation of the primary tumor (eg,
Lu et al 1227
tumor site, staging, pathologic type, preventive therapy for ACBS, and local recurrence before ACBS). The descriptions of the bleeding (eg, origin, left or right side, intra- or extra-oral, and cause of bleeding), and the managements at the onset of ACBS were also collected. Management of ACBS. During the onset, ACLS was performed first. Protection of the airway with oral intubation or tracheotomy was also included if necessary. Restoration of circulating volume was achieved initially by rapid fluid infusion through large-bore peripheral cannulae. Direct compression of the bleeding source with epinephrine packing was performed on all patients. Inotropic agents were administered to the patients if they had persistent shock status (systolic blood pressure <90 mm Hg or diastolic blood pressure <60 mm Hg) without improvement after massive fluid challenge. At our institution, at least one interventional neuroradiologist or cardiovascular surgeon was available within 30 minutes.12 For patients with ACBS, emergent endovascular treatment or surgical ligation, which was the procedure immediately at the time of ACBS onset, was done to reduce the blood loss. For patients without ACBS, selective endovascular treatment was also arranged to prevent an unexpected rupture.4 Critical care in the intensive care unit and inotropic agent use were implemented according to the condition of the patients and the clinicians’ evaluations. The best supportive care was defined as patients that excluded emergent endovascular treatment or surgical ligation. Other aggressive treatments according to clinical conditions, such as fluid hydration, inotropic agents, blood transfusion, and ACLS were still administered. Outcome evaluation. The Glasgow Coma Scale score was evaluated every 4 hours. The complications were recorded according to whether they occurred in the acute or delayed time frame. Acute complications were defined as those that occurred within 72 hours of the onset of ACBS, and those that occurred more than 72 hours after the onset of ACBS were considered as delayed complications. The neutrophil-to-lymphocyte (N/L) ratio differences, which indicate the severity of clinical physiological stress,13,14 were also recorded before and 24 hours after ACBS onset. To understand the influence of ACBS to the long-term survival of HNC, OSs were analyzed for survivors and nonsurvivors. OS was calculated from the date of disease diagnosis to the date of death by any cause, or the date on which the patient was last evaluated. Statistical analysis. Categorical variables were compared using the c2 and Fisher exact tests. The Mann-Whitney test was used for continuous variables. The independent factors of surviving longer than 72 hours were analyzed with univariate and multivariate logistic regressions. We used logistic regression to analyze the risk factors for survival because the end point of univariate and multivariate analysis was to predict survival or not after ACBS rather than the impact of ACBS for survival duration. The factors with P value of <.05 in univariate analyses were included in multivariate logistic regressions. OS was analyzed using the log-rank test and expressed as Kaplan-Meier plots.
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A value of P < .05 was considered statistically significant. All statistical analysis was performed using SPSS statistical software v. 18.0 (SPSS Inc, Chicago, Ill). RESULTS Baseline characteristics between survivor and nonsurvivor patients. Between January 1, 2001 and December 31, 2011, there were 3504 patients with newly diagnosed HNC in our institution. One hundred and three patients (103/3504, 2.9%) who suffered from CBS were identified by imaging/operation finding. They included threatened, impending, and acute subtypes of CBS based on the study by Chaloupka et al.4 Among these, only 45 patients with ACBS, which included acute and profuse hemorrhage without self-limiting over the carotid trunk and immediately emergent treatments where necessary, were enrolled in the present study to analyze the predisposing factors, management, and prognosis. Thirty-four patients (34/45, 75.6%) were treated successfully after aggressive management, whereas 11 patients were treated unsuccessfully. Other patients without ACBS and who accepted preventive or scheduled therapies have been analyzed in our previous study.15 Basic characteristics of both survivor and nonsurvivor patients are presented in Table I. Nearly one-half of patients (19/45, 42.2%) were younger than 50 years old and 91.1% of patients (41/45) were male. Squamous cell carcinoma was the most common pathologic type (38/ 45, 84.4%). There were significant differences between the two groups in tumor site (P ¼ .003), origin of bleeding (P ¼ .048), method of intervention (P ¼ .005), and time to intervention (P ¼ .006). The longest time to intervention of those ACBS patients with invasive procedures was 49 hours. Because there were eight patients who refused any invasive treatments and the time to intervention would be infinite for them, we recorded these cases as up to 60 hours to represent the longest time to intervention. The median times to intervention for both groups were 3.3 hours (0.4-60.0) and 60.0 hours (1.5-60.0), respectively. The survivor patients had a significantly shorter time to intervention than nonsurvivor patients (P ¼ .003). Other factors such as aggressive hydration, intensive critical care, and blood component support were similar (Table I). Angiography resulted in more precise diagnosis of ACBS bleeding site than computed tomography. Fig 1 shows two cases of successful ACBS treatment. A 54-yearold man who was diagnosed with hypopharyngeal cancer had ACBS (Fig 1, A and B). This patient was under palliative chemotherapy because of recurrent disease. The CT scan revealed necrotic soft tissue involving the retropharyngeal region (Fig 1, A). The angiography examination revealed acute extravasation from a pseudoaneurysm of the left middle common carotid artery (CCA) (Fig 1, B). After aggressive management, this patient survived for 7 months from the time of onset. The second case (Fig 1, C and D) involved a 67-year-old man who was diagnosed with glottic cancer and admitted because of poor wound
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healing after neck dissection. The CT scan showed a deep ulcerative wound that was close to the right CCA in the right anterior neck (Fig 1, C). The lesion that was present in the right CCA is shown in Fig 1, D. After emergent endovascular treatment, the patient survived and was followed in the clinical ward for more than 16 months. Univariate and multivariate logistic regression analysis for prognostic factor of ACBS. Univariate analyses of survivor patients also revealed that primary tumor site (oropharynx, P ¼ .006; hypopharynx, P ¼ .048), the origin of bleeding (CCA, P ¼ .031), method of intervention (best supportive care, P ¼ .002), and time to intervention (>12 hours, P ¼ .020) were significant prognostic factors. Multivariate analyses indicated that bleeding of the CCA was the only independent factor for survivor patients (odds ratio, 25.951; 95% confidence interval [CI], 1.373490.441; P < .030) (Table II). Because of the small number of patients enrolled in this study, the characteristics of ACBS patients were unevenly distributed. Such distribution pattern resulted in the large range of 95% CI. Consciousness level, the use of inotropic agents, and N/L ratio change are important predictors for the outcomes of ACBS. Under aggressive treatment, the incidence of acute complications was similar in both groups. Aspiration pneumonia and stroke/transient ischemic attack were the most common complications. More patients in the survivor group had a better consciousness level (Glasgow coma score $9) than patients in the nonsurvivor group 24 hours after ACBS onset (P ¼ .000; Table III). Inotropic agent used 24 hours after ACBS was significantly higher in nonsurvivor patients (P ¼ .007). The hemoglobin concentration was recorded to evaluate the hemodynamic status of the patients, which did not differ between the two groups. Because the N/L ratio reflects the level of severe physiological stressors such as massive bleeding or critical condition,13-17 the baseline and 24-hour N/L ratios were assessed. There were similar N/L ratios between the groups at the onset of ACBS (P ¼ .605); however, both groups had a higher N/L ratio than the baseline 24 hours after onset (P ¼ .019 and .012; Fig 2). The N/L ratio 24 hours after onset was higher in the nonsurvivor group compared with the survivor group (P ¼ .007; Table III; Fig 2). Outcomes of the various treatment modalities. Except eight patients without aggressively invasive treatment, there were 30 patients who received endovascular therapy and seven patients received surgical treatment. Patients would receive surgical ligation if radical neck dissection was done recently without the wound healing completely. The most frequent etiology of bleeding after radical neck dissection was tumor involvement (4/7; 57.1%). Others included fistula formation (1/7; 14.3%), local inflammation/necrosis (1/7; 14.3%), and postoperation complication (1/7; 14.3%). Surgical treatment showed a higher mortality rate than endovascular therapy. Mortality rate of best supportive care, endovascular therapy, and surgical ligation were 75% (6/8), 10% (3/30), and 28.6% (2/7), respectively.
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Table I. Continued.
Table I. Basic characteristics of patients with ACBS
Characteristics Age, years $50 <50 Sex Male Female Tumor site Oral cavity Nasopharynx Oropharynx Hypopharynx Larynx Othersa Initial T stage #T2 >T2 Unknownb Initial N stage N0 Nþ Unknownb Initial M stage M0 M1 Pathologic type Squamous cell carcinoma Adenosquamous carcinoma Nonkeratinizing carcinoma Leiomyosarcoma Carcinoma, undifferentiated Prevent therapy for ACBS None Stent insertion Embolization Stent insertion and embolization Surgical procedure Local recurrence before ACBS Yes No Origin of bleeding ICA ECA or its branches CCA Carotid bifurcation Combinationc Unknownd Side of ACBS Left Right Site of bleeding Intraoral Extraoral Cause of bleeding Tumor relatede Pseudoaneurysm Soft tissue inflammation Fistula formation Postoperative complication Method of intervention Best supportive care Stent insertion Embolization
Survivor patients (n ¼ 34)
Nonsurvivor patients P (n ¼ 11) value .273
21 (61.8%) 13 (38.2%)
5 (45.5%) 6 (54.5%) .311
30 (88.2%) 11 (100.0%) 4 (11.8%) 0 (0.0%) .003 8 2 4 16 1 3
(23.5%) (5.9%) (11.8%) (47.1%) (2.9%) (8.8%)
0 2 6 1 2 0
(0.0%) (18.2%) (54.5%) (9.1%) (18.2%) (0.0%) .520
9 (26.5%) 24 (70.6%) 1 (2.9%)
4 (36.4%) 6 (54.5%) 1 (9.1%) .141
6 (17.6%) 26 (76.5%) 2 (5.9%)
5 (45.5%) 5 (45.5%) 1 (9.1%) .422
31 (91.2%) 11 (100.0%) 3 (8.8%) 0 (0.0%) .207 30 1 1 1 1
(88.2%) (2.9%) (2.9%) (2.9%) (2.9%)
8 0 2 0 1
(72.7%) (0.0%) (18.2%) (0.0%) (9.1%)
28 0 2 2
(82.4%) (0.0%) (5.9%) (5.9%)
9 1 1 0
(81.8%) (9.1%) (9.1%) (0.0%)
.341
2 (5.9%)
0 (0.0%)
20 (58.8%) 14 (41.2%)
8 (72.7%) 3 (27.3%)
5 16 7 4 1 1
0 2 5 1 0 3
.325
Characteristics
Survivor patients (n ¼ 34)
Stent insertion and 4 (11.8%) embolization Surgical procedure 5 (14.7%) Time to intervention, hours #3 15 (44.1%) >3 and #6 7 (20.6%) >6 and #12 4 (11.8%) >12 6 (17.6%) Patients refuse 2 (5.9%) Total fluid challenge in the first 24 hours, L #2 1 (4.2%) >2 and #3 5 (20.8%) >3 and #4 4 (16.7%) >4 14 (58.3%) No. of patients available 24 Total fluid output in the first 24 hours, L #2 9 (37.5%) >2 and #3 7 (29.2%) >3 and #4 3 (12.5%) >4 5 (20.8%) No. of patients available 24 The blood component support in the first 24 hours, U PRBC 4 (0-28) Plt. pheresis 0 (0-4) FFP 2 (2-16) Intensive critical care 20 (58.8%)
Nonsurvivor patients P (n ¼ 11) value 0 (0.0%) 2 (18.2%) .006 1 2 1 1 6
(9.1%) (18.2%) (9.1%) (9.1%) (54.5%) .667
0 3 1 3
(0.0%) (42.9%) (14.3%) (42.9%) 7 .188
3 0 3 1
(42.9%) (0.0%) (42.9%) (14.3%) 7
4 0 4 5
(4-16) (0-4) (4-14) (45.5%)
.369 .429 .387 .333
ACBS, Acute carotid blowout syndrome; CCA, common carotid artery; ECA, external carotid artery; ICA, internal carotid artery; FFP, fresh frozen plasma; Plt, platelet; PRBC, packed red blood cells. a Others: carcinoma of unknown primary, nasal antrum, and ethmoid sinus cancer. b Unknown cases were diagnosed at another hospital without initial data. c The origins of bleeding involved left ICA, lingular artery and superior thyroid arteries. d Patients and their families refused invasive procedures at ACBS onset. e Including tumor necrosis or tumors involving the vessels.
.048 (14.7%) (47.1%) (20.6%) (11.8%) (2.9%) (2.9%)
(0.0%) (18.2%) (45.5%) (9.1%) (0.0%) (27.3%) .466
18 (52.9%) 16 (47.1%)
5 (45.5%) 6 (54.5%)
21 (61.8%) 13 (38.2%)
8 (72.7%) 3 (27.3%)
13 15 3 2 1
7 3 0 1 0
.390 .522 (38.2%) (44.1%) (8.8%) (5.9%) (2.9%)
(63.6%) (27.3%) (0.0%) (9.1%) (0.0%) .005
2 (5.9%) 3 (8.8%) 20 (58.8%)
6 (54.5%) 0 (0.0%) 3 (27.3%)
The detailed results are shown in Table I. Because the number of patients was too small in each treatment group, the modalities were hard to compare with each other. For patients who received embolization and surgical ligation, the most frequent complication was aspiration pneumonia (14/23, 60.9% for embolization; 3/7, 42.9% for surgical ligation). Delayed stroke/transient ischemic attack was the main problem of patients with stent insertion (1/3, 33.3%). Recurrent CBS treated with endovascular therapy and surgical ligation were 20% (6/30) and 0% (0/7), respectively. Long-term survival of patients after successful management of ACBS. To understand the influence of ACBS on the disease course, Kaplan-Meier analyses were used to evaluate the long-term survival trends. The median overall survival of survivors and nonsurvivors were 12.1 (range, 3.7-118.7; 95% CI, 4.33-54.87) and 11.9 (range, 0.7-53.5; 95% CI, 5.78-25.69) months, respectively (P ¼ .092) (Fig 3).
1230 Lu et al
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Fig 1. Computed tomography (CT) and angiography findings of acute carotid blowout syndrome (ACBS). In (A) and (B), a 54-year-old man who was diagnosed with hypopharyngeal cancer and under palliative chemotherapy treatment presented with acute left common carotid artery (CCA) CBS. A CT scan revealed necrotic soft tissue involving the left CCA (thick black arrow). The angiography results revealed acute extravasation from a pseudoaneurysm of the left middle CCA (thick white arrow). In (C) and (D), a 67-year-old man with glottic cancer was evaluated for poor wound healing following neck dissection. A deep ulcerative wound was found in the right anterior neck. The lesion was close to the right CCA (thin black arrow). Acute rupture in the right CCA was found on angiography (thin white arrow).
DISCUSSION ACBS, usually a life-threatening complication of HNC, is accompanied with unexpectedly massive bleeding and high mortality/morbidity rates.4,8 In this study, location of primary tumor and bleeding sites, as well as early and aggressive interventions persistently showed importance for survivor patients. The changes in the consciousness level, inotropic agent usage, and N/L ratio after 24 hours were the major factors that were predictive of ACBS outcomes. Multivariate analysis showed that CCA bleeding was the significantly prognostic factor for long-term survival. Surgical ligation and endovascular therapy are the main treatments for CBS patients. Surgical management was the first option for CBS patients traditionally.18 Because ACBS was an early complication following radical neck dissection, some patients would receive surgical ligation if radical neck dissection was done recently without the wound healing completely.18,19 Raising skin flaps in the neck was quick and easy to expose deep cervical fascia and to check bleeding, this procedure was also the emergent method to stop bleeding. After removing skin flaps, deep cervical fascia and carotid sheath, which coated internal jugular vein, vagus nerve, and carotid artery, were dissected. After
identifying the source of bleeding, the rupture site was repaired, and the carotid artery was ligated. If the border of the artery or other vital organs could not be divided clearly because of severe fibrosis, we would keep finding carotid artery through the pulsation. Then, the CCA and the furcation area could be reached. Debridement was also done if necrotic tissue was found. The operative wound was irrigated with beta-iodine and normal saline to minimize the contamination. Then, the wound was closed with Vicryl and nylon. After completing the procedure, patients were sent to the intensive care unit for postoperative care. However, open surgical techniques were gradually replaced with endovascular therapy because of high mortality/morbidity after surgical ligation.18,20 In addition, direct exploration and repair of the previously irradiated field were also difficult for surgeons to approach.19 Therefore, endovascular therapy, including destructive (embolization) and constructive (stent grafting) techniques, are gaining popularity for the treatment of ACBS recently. More and more articles have discussed the effect and outcomes of endovascular therapy.19,20 The morbidity/mortality rates are significantly decreased in endovascular therapy than in surgical treatment.20,21
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Lu et al 1231
Table II. Univariate and multivariate logistic regression analysis for the prognostic factor of ACBS Multivariate Variable Age, $50 years Male Tumor site Oral cavity Nasopharynx Oropharynx Hypopharynx Larynx Pathological type Squamous cell carcinoma Adenosquamous carcinoma Nonkeratinizing carcinoma Leiomyosarcoma Carcinoma, undifferentiated Prevent therapy for ACBS Treatment just before ACBS Palliative chemotherapy Concurrent chemoradiotherapy None Origin of bleeding ICA ECA or its branches CCA Carotid bifurcation Combinationa Cause of bleeding Tumor relatedb Pseudoaneurysm Soft tissue inflammation Fistula formation Postoperative complication Method of intervention Best supportive care Stent insertion Embolization Stent insertion and embolization Surgical procedure Time to intervention, hours #3 >3 and #6 >6 and #12 >12 Local recurrence before ACBS
Univariate P value
P value
OR (95% CI)
.229 .099
5.369 (0.347-83.090) 0.056 (0.002-1.717)
.030
25.951 (1.373-490.441)
.394
4.759 (0.132-171.649)
.783
1.494 (0.086-25.981)
.345 .999 .999 .235 .006 .048 .120 .230 1.000 .120 1.000 .413 .968 .243 .999 .433 .999 .242 .031 .977 1.000 .149 .327 .999 .713 1.000 .002 .999 .079 .999 .783 .061 .862 .807 .020 .412
ACBS, Acute carotid blowout syndrome; CCA, common carotid artery; CI, confidence interval; ECA, external carotid artery; ICA, internal carotid artery; OR, odds ratio. a The origins of bleeding involved left ICA, lingular artery, and superior thyroid arteries. b Including tumor necrosis or tumors involving the vessels.
There are two kinds of endovascular therapies, including deconstructive and constructive. However, there were limited data that compare the outcomes between deconstructive and constructive treatments for patients with ACBS.20 Current evidence shows that there was no significant difference in technical and hemostatic outcomes between the reconstructive and deconstructive endovascular methods19-21 because permanent vessel occlusion resulted in higher immediately cerebral ischemia and stent grafting induced the more potentially delayed complications, such as infection, rebleeding, and stent thrombosis.18,20 In our practice, patients whose pathologic
lesions involved the branches of external carotid artery were only administered with deconstructive management.19 Those involving the main trunk of the carotid artery received either deconstructive treatment or constructive treatment according to the result of a balloon occlusion test (BTO), which evaluates blood supply from intracranial collateral circulation.22 Stent grafting was considered if the circle of Willis was incomplete, or an unstable clinical condition precluded BTO. Because stent grafts have to be self-paid by patients in Taiwan, the cost effectiveness should also be explained. Stent grafting was also suggested if the areas of pathologic involvement
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1232 Lu et al
Table III. Outcome characteristics of patients with ACBS Variable Glasgow coma score after 24 hours $9 6-8 #5 Unknown Inotropic agent use 24 hours after ACBS No. of patients evaluated Acute complicationsa Stroke/TIA Aspiration pneumonia Femoral hematoma Delayed complicationsa Stroke/TIA Aspiration pneumonia Brain abscess Wound infection Empyema Femoral hematoma Upper gastrointestinal bleeding due to antiplatelet agents Serum markers 24 hours after ACBS onset Complete blood count WBC (103 cells/mL) >10.0 Hgb (g/dL) <11.0 PLT (103 cells/mL) >400.0 No. of patients evaluated Differential count N/L ratio Monocyte (cells/mL) >1000 No. of patients evaluated
Survivor patients (n ¼ 34)
Nonsurvivor patients (n ¼ 11)
P value .000
29 2 4 3 11
(73.5%) (5.9%) (11.8%) (8.8%) (32.4%) 34
3 (8.8%) 13 (38.2%) 1 (2.9%)
0 3 6 2 7
(0.0%) (27.3%) (54.5%) (18.2%) (87.5%) 8
.007
0 (0.0%) 4 (36.4%) 0 (0.0%)
.422 .602 .756
NA NA NA NA NA NA NA
NA NA NA NA NA NA NA
19 (63.3%) 5 (16.7%) 1 (3.3%) 30
7 (100%) 3 (42.9%) 1 (14.3%) 7
.064 .156 .347
20.7 (5.9-48.5) 10 (35.7%) 28
48.5 (10.5-93.0) 3 (42.9%) 7
.007 .525
2 4 1 2 1 1 2
(5.9%) (11.8%) (2.9%) (5.9%) (2.9%) (2.9%) (5.9%)
ACBS, Acute carotid blowout syndrome; Hgb, hemoglobin; NA, not analyzed; N/L, neutrophil-to-lymphocyte; PLT, platelet count; TIA, transient ischemic attack; WBC, white blood cell. a Acute complications were defined as complications that occurred within 72 hours after massive bleeding; delayed complications were defined as those that occurred after more than 72 hours.
were too large to be embolized, so that embolizing to the external carotid artery or its branches and keeping the blood supply from CCA to the internal carotid artery (ICA) with stent grafting were considered. There are some reasons that permanent vessel occlusion remains the standard therapy for ACBS patients in our institution. First, because delayed complications and long-term outcomes are unclear with stent grafting,18,20 constructive treatment has to be self-paid by patients in Taiwan and the cost effectiveness of stent grafting should be evaluated. Second, whether the ability of stopping bleeding is comparable in stent grafting is still controversial.15,22,23 So, the constructive treatment was only applied for patients with the incomplete circle of Willis, precluding an occlusion test, or intolerant BTO, that when carotid occlusion poses an unusually high risk of neurologic morbidity.24 Initial resuscitation in a minimal amount of time and identification of the source of bleeding with immediate intervention are critical for the management of massive bleeding events.25 These management strategies result in successful patient survival and hemostasis.19 At our institution, interventional teams were available within 30 minutes after they were informed about a massive bleeding event. Other multidisciplinary teams were also placed on all-day
standby.12 Therefore, at the onset of ACBS, ACLS was provided immediately in accordance with the patients’ needs, and invasive interventions were prepared well in advance. Blood component support and critical care after these interventions were more readily available at our hospital compared with other local medical institutions. With multidisciplinary cooperation, we were able to provide a high level of medical care for all patients with ACBS and achieved a good success rate. The primary tumor site and origin of bleeding significantly influenced the patient outcomes. In a previous study, the luminal vessel diameter impacted the outcome of ACBS, as it is relatively difficult to perform interventions and control hemostasis in vessels with large luminal diameters.26 Moreover, patients with ICA or CCA involvement are more likely to experience immediate/delayed cerebral ischemia and more blood loss,24 which leads to high mortality/morbidity rates. Another possible explanation is that a primary tumor that is located far from the ICA or CCA is less likely to directly involve these arteries, which also results in better survival outcomes. ACBS is a rare and rapidly progressive complication. ACBS patients always suffer from loss of consciousness, cardiac arrest, or hypovolemic shock; ACLS is needed at
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Fig 2. Neutrophil-to-lymphocyte (N/L) ratio before and after acute carotid blowout syndrome (ACBS) in survivor or nonsurvivor patients. The N/L ratios were significantly higher 24 hours after ACBS onset relative to those at initial onset (P ¼ .012 and .019 in both groups, respectively). The N/L ratio did not differ between both groups at initial onset (P ¼ .527), but was significantly much higher in the group with nonsurvivors than in the group with survivors after 24 hours (P ¼ .007).
the time of onset. Because of a critical complication and difficulty to manage, patients may expire in a very short period of time without enough follow-up. Hemodynamic status is an important factor that is capable of predicting the outcome of massive bleeding because it results in prolonged hypovolemic shock and severe vasoconstriction. This condition also induces multiorgan failure and tissue ischemia.25,27 However, it is difficult to evaluate hemodynamic status using blood pressure measurements and the volume of blood transfused in practice, as vessel constriction and the use of inotropic agents might mask the real hemodynamic status. Some articles have proposed the prognostic factors to evaluate patients with severe shock, but they were inappropriate for ACBS patients because of short clinical courses to be followed up.28-34 The use of N/L ratio is easily assessed, and the data are quickly available. Therefore, we examined several serum markers that could reflect the severity of systemic inflammation and physiological stress.13,14 Zahorec et al used the N/L ratio as a parameter for the intensity of stress/systemic inflammation in critically ill patients following shock, multiple trauma, major surgery, or sepsis.13 Physiological stress is reflected as systemic inflammation,35 which mediates complex interactions that influence the N/L ratio.14 Therefore, in patients who have systemic stress/inflammation and local endothelial injury, the N/L ratio indeed reflects the degree of endovascular injury and disease
Lu et al 1233
Fig 3. Overall survival of survivors and nonsurvivors. The median overall length of survival of survivors and nonsurvivors was 12.1 (range, 3.7-118.7; 95% confidence interval [CI], 4.33-54.87) and 11.9 (range, 0.7-53.5; 95% CI, 5.78-25.69) months, respectively (P ¼ .092).
severity.16,17 The results of the current study also suggested that patients who did not survive had higher levels of physiological stress reflected by an increase in the N/L ratio. In previous studies, the most common cause of mortality for patients that survived ACBS is disease progression rather than related complications.12,26 Our study also showed that the long-term progression-free survival and OS of ACBS patients were similar to those of patients without ACBS.36,37 With successful treatment, long-term survival can be achieved in patients with ACBS. There were some limitations in this study. The first was the small number of patients and inherent selection bias. Because this was a retrospective study, patient selection was performed according to medical records. However, the terms, including tumor bleeding, carotid blowout, oral bleeding, or neck wound bleeding, were described as massive bleeding in the charts. Therefore, it was difficult to identify the true ACBS cases. In our study, in addition to massive bleeding, ACBS was identified according to CT/CTA, invasive carotid angiography, or operation findings. Patients who were diagnosed with bleeding without CT/CTA, invasive carotid angiography, or operation findings were excluded from the analysis. In conclusion, aggressive and early interventions are important for the management of ACBS. Other factors such as the source of bleeding and N/L ratio changes
1234 Lu et al
were prognostic factors for patient outcomes. Bleeding from CCA is an independent prognostic factor. With successful management, long-term survival rates of these patients could be achieved that are comparable with HNC patients without ACBS. The authors thank Miss Ling-Chen Tai in statistical consultation.
AUTHOR CONTRIBUTIONS Conception and design: KC, MC, PC, ST, LW, PC, MY Analysis and interpretation: HL Data collection: HL Writing the article: HL Critical revision of the article: PC, MY Final approval of the article: PC, MY Statistical analysis: HL Obtained funding: Not applicable Overall responsibility: PC, MY
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32. Scarcello E, Ferrari M, Rossi G, Berchiolli R, Adami D, Romagnani F, et al. A new preoperative predictor of outcome in ruptured abdominal aortic aneurysms: the time before shock (TBS). Ann Vasc Surg 2010;24:315-20. 33. Nakayama A, Morita H, Miyata T, Hoshina K, Nagayama M, Takanashi S, et al. Predictors of mortality after emergency or elective repair of abdominal aortic aneurysm in a Japanese population. Heart Vessels 2012 December 30; [Epublication ahead of print]. 34. Robinson WP, Schanzer A, Li Y, Goodney PP, Nolan BW, Eslami MH, et al. Derivation and validation of a practical risk score for prediction of mortality after open repair of ruptured abdominal aortic aneurysms in a US regional cohort and comparison to existing scoring systems. J Vasc Surg 2013;57:354-61.
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Submitted Feb 20, 2013; accepted Apr 23, 2013.