A historical prospective cohort study of carotid artery stenosis after radiotherapy for head and neck malignancies

PURPOSE: To determine carotid artery stenosis incidence after radiotherapy for head-and-neck neoplasms. METHODS AND MATERIALS: This historical prospective cohort study comprised 44 head-and-neck cancer survivors who received unilateral neck radiotherapy between 1974 and 1999. They underwent bilateral carotid duplex ultrasonography to detect carotid artery stenosis. RESULTS: The incidence of significant carotid stenosis (8 of 44 [18%]) in the irradiated neck was higher than that in the contralateral unirradiated neck (3 of 44 [7%]), although this difference was not statistically significant (p = 0.13). The rate of significant carotid stenosis events increased as the time after radiotherapy increased. The risk of ipsilateral carotid artery stenosis was higher in patients who had undergone a neck dissection vs. those who had not. Patients with significant ipsilateral stenosis also tended to be older than those without significant stenosis. No other patient or treatment variables correlated with risk of carotid artery stenosis. CONCLUSIONS: For long-term survivors after neck dissection and irradiation, especially those who are symptomatic, ultrasonographic carotid artery screening should be considered.     

鼻咽癌放疗致颈动脉损伤的研究进展

颈部放疗是防治鼻咽癌颈部淋巴结转移的重要手段,但放射线可直接或间接损伤血管,加速动脉粥样硬化进程,进而导致颈动脉狭窄,增加放疗后短暂性脑缺血和脑卒中发生的风险。目前多采用彩色多普勒超声检测颈动脉的变化情况,并通过积极预防及减少危险因素来降低颈动脉狭窄的发生率。颈动脉狭窄可采用药物早期干预及手术治疗。本文就放疗致颈动脉损伤的研究现状进行综述。     

Clinical Features of Radiation-induced Carotid Atherosclerosis

Carotid arteries frequently receive significant incidental doses of radiation during the treatment of malignant diseases, including head and neck cancer, breast cancer and lymphoma. Vascular injury after treatment may result in carotid artery stenosis and increased risk of neurological sequelae, such as stroke and transient ischaemic attack. The long latent interval from treatment to the development of clinical complications makes investigation of this process difficult, particularly in regard to the design of interventional clinical studies. Nevertheless, there is compelling clinical evidence that radiation contributes to carotid atherosclerosis. This overview examines the effect of radiotherapy on the carotid arteries, the underlying pathological processes and their clinical manifestations. The use of serum biomarkers in risk-prediction models and the potential value of new imaging techniques as tools for defining earlier surrogate end points will also be discussed.     

治疗135例脑恶性星形细胞瘤的探讨

目的 :分析脑恶性星形细胞瘤手术后采用单纯放射治疗及放疗加颈动脉化疗的疗效。材料与方法 :1987年 8月～ 1992年 11月收治 135例脑恶性星形细胞瘤。分两组治疗 ,单放组 71例 ,综合组 6 4例。两组放疗剂量 DT5 5～ 70 Gy。综合组术后 4～ 15天行颈动脉化疗 ,10～ 15天后行放疗 ,放疗结束再化疗 1～ 3次。结果 :单放组中位生存期 17.5个月 ,综合组为 31.9个月。其中效果最好的是多形性胶质母细胞瘤。33例中 2 ,3,5年生存率分别 70 %、36 %、15 %。结论 :脑恶性星形细胞瘤术后采用综合组治疗方案疗效满意     

Traumatic dissection of extracranial internal carotid artery and subclavian artery

A case of a young, adult male presenting with acute post-traumatic dissection involving the left internal carotid and subclavian artery is described.     

Aneurysm of the common carotid artery as a sequel of puncture angiography

The case of a 60-year-old man with a large aneurysm of the common carotid artery, which manifested five months after puncture angiography, is described. This was successfully managed by aneurysm exclusion and aortocarotid bypass. The etiology of the aneurysm is discussed.     

Single-dose and fractionated irradiation promote initiation and progression of atherosclerosis and induce an inflammatory plaque phenotype in ApoE(-/-) mice

PURPOSE: Increased risk of atherosclerosis and stroke has been demonstrated in patients receiving radiotherapy for Hodgkin's lymphoma and head-and-neck cancer. We previously showed that 14 Gy to the carotid arteries of hypercholesterolemic ApoE(-/-) mice resulted in accelerated development of macrophage-rich, inflammatory atherosclerotic lesions. Here we investigate whether clinically relevant fractionated irradiation schedules and lower single doses also predispose to an inflammatory plaque phenotype. METHODS AND MATERIALS: ApoE(-/-) mice were given 8 or 14 Gy, or 20 x 2.0 Gy in 4 weeks to the neck, and the carotid arteries were subsequently examined for presence of atherosclerotic lesions, plaque size, and phenotype. RESULTS: At 4 weeks, early atherosclerotic lesions were found in 44% of the mice after single doses of 14 Gy but not in age-matched controls. At 22 to 30 weeks after irradiation there was a twofold increase in the mean number of carotid lesions (8-14 Gy and 20 x 2.0 Gy) and total plaque burden (single doses only), compared with age-matched controls. The majority of lesions seen at 30 to 34 weeks after fractionated irradiation or 14-Gy single doses were granulocyte rich (100% and 63%, respectively), with thrombotic features (90% and 88%), whereas these phenotypes were much less common in age-matched controls or after a single dose of 8 Gy. CONCLUSIONS: We showed that fractionated irradiation accelerated the development of atherosclerosis in ApoE(-/-) mice and predisposed to the formation of an inflammatory, thrombotic plaque phenotype.     

13例头颈部恶性肿瘤行大隐静脉颈动脉置换术患者的围手术期护理

目的探讨头颈部恶性肿瘤患者行大隐静脉颈动脉置换手术围手术期的护理方法。方法选取2018年9月至2019年12月间中国医学科学院肿瘤医院收治的13例头颈部恶性肿瘤行大隐静脉颈动脉置换术患者,在患者手术治疗前进成立多学科治疗小组、心理护理和颈总动脉压迫试验等术前护理,手术后采用术后护理,包括血压管理、病情观察、抗凝药物效果观察、体位护理、气道管理、营养管理、心理护理和并发症预防,分析总结头颈部恶性肿瘤患者行大隐静脉颈动脉置换手术的围手术期护理方法。结果 11例患者术后未出现脑卒中和偏瘫等严重并发症,均顺利出院;1例患者出现轻微脑梗塞,治疗观察四周后出院,1例患者出现急性心肌梗塞,转入专科医院治疗四周后顺利出院。结论对头颈部恶性肿瘤行大隐静脉动脉置换术患者行针对性围手术期护理,可提高手术成功率,减少术后并发症,促进患者康复。     

颈动脉灌注尼莫司汀化疗加立体定向适形放疗治疗脑胶质瘤的研究

背景与目的：脑胶质瘤很难经手术彻底切除，术后易复发。本研究探讨经颈动脉灌注尼莫司汀化疗加立体定向适形放疗针对术后脑胶质瘤的临床治疗效果。方法：对35例经手术切除脑胶质瘤的患者，于术后7-21天行颈动脉灌注尼莫司汀1次．每次2．5mg／kg，每个月1次，3次为1个疗程。同时术后第14-28天开始行立体定向适形放疗，约5～6周后结束。术后6个月再根据复查情况决定是否进行第2个疗程治疗。结果：随访6个月至4年，肿瘤消失12例（34．2％），肿瘤明显缩小10例（28．5％），复发经2次手术而且行本方案治疗后肿瘤消失4例（11．4％），病情恶化4例（11．4％），死亡5例（14．2％）。结论：经颈动脉灌注尼莫司汀化疗加立体定向适形放疗对术后脑胶质瘤具有明显的辅助治疗作用。     

Isolated intrapetrous carotid canal atraumatic internal carotid artery dissection: MRI and digital subtraction angiography findings

A case of spontaneous internal carotid artery (ICA) dissection confined to the intrapetrous carotid canal that was confirmed by angiography and magnetic resonance imaging is presented. Isolated dissection involving the intrapetrous ICA is rare; however, whenever arterial dissection is a consideration, specific review of imaging in this region is warranted.     

Anti-inflammatory and anti-thrombotic intervention strategies using atorvastatin, clopidogrel and knock-down of CD40L do not modify radiation-induced atherosclerosis in ApoE null mice

Background and purpose

We previously showed that irradiating the carotid arteries of ApoE^−/− mice accelerated the development of macrophage-rich, inflammatory and thrombotic atherosclerotic lesions. In this study we investigated the potential of anti-inflammatory (atorvastatin, CD40L knockout) and anti-thrombotic (clopidogrel) intervention strategies to inhibit radiation-induced atherosclerosis.

Material and methods

ApoE^−/− mice were given 0 or 14 Gy to the neck and the carotid arteries were harvested at 4 or 28 weeks after irradiation. Atorvastatin (15 mg/kg/day) or clopidogrel (20 mg/kg/day) was given in the chow; control groups received regular chow. Clopidogrel inhibited platelet aggregation by 50%. CD40L^−/−/ApoE^−/− and ApoE^−/− littermates were also given 0 or 14 Gy to the neck and the carotid arteries were harvested after 30 weeks.

Results

Clopidogrel decreased MCP-1 expression in the carotid artery at 4 weeks after irradiation. Expression of VCAM-1, ICAM-1, thrombomodulin, tissue factor and eNOS was unchanged in atorvastatin and clopidogrel-treated mice. Neither drug inhibited either age-related or radiation-induced atherosclerosis. Furthermore, loss of the inflammatory mediator CD40L did not influence the development of age-related and radiation-induced atherosclerosis.

Conclusions

The effects of radiation-induced atherosclerosis could not be circumvented by these specific anti-inflammatory and anti-coagulant therapies. This suggests that more effective drug combinations may be required to overcome the radiation stimulus, or that other underlying mechanistic pathways are involved compared to age-related atherosclerosis.     

Comparison of two Doppler ultrasound criteria for grading cervical internal carotid artery stenosis

In a review of 49 carotid arteries that had been assessed by ultrasound and angiography, two Doppler criteria were compared for accuracy in grading internal carotid artery (ICA) stenosis. The Seattle criteria for Doppler spectral analysis and the internal-to-common carotid artery peak systolic velocity ratio were of similar accuracy. When used in combination, there was an increase in sensitivity compared with the use of a single criterion. The velocity ratio had a higher sensitivity for detection of high-grade stenosis, but it tended to overestimate the grade of stenosis more than the Seattle criteria. To increase the sensitivity for detection of severe stenosis, the criteria should be used together and the higher grade of stenosis should be taken if there is a mismatch in assessment.     

Irradiation of existing atherosclerotic lesions increased inflammation by favoring pro-inflammatory macrophages

Background and purpose

Recent studies have shown an increased incidence of localized atherosclerosis and subsequent cardiovascular events in cancer patients treated with thoracic radiotherapy. We previously demonstrated that irradiation accelerated the development of atherosclerosis and predisposed to an inflammatory plaque phenotype in young hypercholesterolemic ApoE^−/− mice. However, as older cancer patients already have early or advanced stages of atherosclerosis at the time of radiotherapy, we investigated the effects of irradiation on the progression of existing atherosclerotic lesions in vivo.

Material and methods

ApoE^−/− mice (28 weeks old) received local irradiation with 14 or 0 Gy (sham-treated) at the aortic arch and were examined after 4 and 12 weeks for atherosclerotic lesions, plaque size and phenotype. Moreover, we investigated the impact of irradiation on macrophage phenotype (pro- or anti-inflammatory) and function (efferocytotic capacity, i.e. clearance of apoptotic cells) in vitro.

Results

Irradiation of existing lesions in the aortic arch resulted in smaller, macrophage-rich plaques with intraplaque hemorrhage and increased apoptosis. In keeping with the latter, in vitro studies revealed augmented polarization toward pro-inflammatory macrophages after irradiation and reduced efferocytosis by anti-inflammatory macrophages. In addition, considerably more lesions in irradiated mice were enriched in pro-inflammatory macrophages.

Conclusions

Irradiation of existing atherosclerotic lesions led to smaller but more inflamed plaques, with increased numbers of apoptotic cells, most likely due to a shift toward pro-inflammatory macrophages in the plaque.     

肝动脉插管化疗与放疗交替进行治疗原发性肝癌

 目的 观察Ⅱ期不可手术切除的原发性肝癌施行肝动脉结扎、肝动脉插管化疗及常规分割放疗的疗效。方法 全组65例为经剖腹探查判定不可手术切除的Ⅱ期肝癌，取活检并作了肝动脉结扎、肝动脉插管化疗及常规分割放疗。结果 AFP定量下降1/2以上率、1、3、5年生存率分别为67.6%、73.9%、41.5%、9.2%，PR率、二步手术切除率分别为70.8%、12.3%。结论 采用肝动脉结扎、低剂量顺铂（PDD）10mg动脉化疗6天/周与常规分割放疗5天/周交替夹心、互为协同的治疗方案能有效地减轻症状、缩小瘤体、提高手术切除率、延长生存期，且操作较为简单，易于掌握。     

Understanding Radiation-induced Cardiovascular Damage and Strategies for Intervention

There is a clear association between therapeutic doses of thoracic irradiation and an increased risk of cardiovascular disease (CVD) in cancer survivors, although these effects may take decades to become symptomatic. Long-term survivors of Hodgkin's lymphoma and childhood cancers have two-fold to more than seven-fold increased risks for late cardiac deaths after total tumour doses of 30–40 Gy, given in 2 Gy fractions, where large volumes of heart were included in the field. Increased cardiac mortality is also seen in women irradiated for breast cancer. Breast doses are generally 40–50 Gy in 2 Gy fractions, but only a small part of the heart is included in the treatment fields and mean heart doses rarely exceeded 10–15 Gy, even with older techniques. The relative risks of cardiac mortality (1.1–1.4) are consequently lower than for Hodgkin's lymphoma survivors. Some epidemiological studies show increased risks of cardiac death after accidental or environmental total body exposures to much lower radiation doses. The mechanisms whereby these cardiac effects occur are not fully understood and different mechanisms are probably involved after high therapeutic doses to the heart, or part of the heart, than after low total body exposures. These various mechanisms probably result in different cardiac pathologies, e.g. coronary artery atherosclerosis leading to myocardial infarct, versus microvascular damage and fibrosis leading to congestive heart failure. Experimental studies can help to unravel some of these mechanisms and may identify suitable strategies for managing or inhibiting CVD. In this overview, the main epidemiological and clinical evidence for radiation-induced CVD is summarised. Experimental data shedding light on some of the underlying pathologies and possible targets for intervention are also discussed.     

α1胸腺肽减轻放射性肺损伤

背景与目的放射性肺损伤是限制肺癌放疗疗效提高的主要因素之一,胸腺肽与放疗同时使用是否会加重放射性肺损伤尚不明确。本研究旨在用小鼠的放射性肺损伤模式评价α1胸腺肽对放射性肺损伤的影响。方法 33只雌性C57BL/6J鼠,体重19g左右,分为正常空白对照(C)组、单纯照射(RT)组、α1胸腺肽加照射(T+RT)组。用小鼠死亡比例、体重、胸水、肺系数、肺泡灌洗液蛋白含量和细胞计数、肺泡壁肿胀和细胞浸润及肺纤维化积分作为观察指标来评价三组间的差异。结果 T+RT组与RT组小鼠死亡比例分别为3/14、2/10,死亡时间均为23周-24周。第24周时解剖发现RT组有一侧大量胸腔积液,一侧中等量积液,T+RT组未见明显胸腔积液。T+RT组肺系数、肺泡灌洗液蛋白含量和细胞总数、中性粒细胞计数均在第8周低于RT组,但巨噬细胞数第8周时T+RT组高于RT组。第24周T+RT组肺系数、肺泡灌洗液蛋白含量和细胞总数、中性粒细胞数、肺泡壁肿胀和细胞浸润及肺纤维化积分均明显低于RT组。C组肺泡灌洗液蛋白含量和细胞总数、肺泡壁肿胀与炎性细胞浸润均较低,未发生明显肺纤维化。结论α1胸腺肽可能具有一定的防治放射性肺损伤的作用。     

Late Cerebrovascular Disease after Radiation Therapy – Report of Two Cases and a Review of the Literature

Symptomatic vascular disease induced by radiation therapy has become a problem, increasingly recognised by the cancer therapist in recent years. Two further cases of this entity are reported herein, followed by a detailed literature review of histopathologic changes seen in experimentally-and clinically-iiradiated blood vessels the clinical and radiological features, treatment and natural history of large vessel, especially cerebral, disease attributed to therapeutic irradiation.     

颈淋巴结阴性鼻咽癌患者颈部的放射治疗

本文分析１９８８年１月至１２月在我科放疗前有ＣＴ检查的Ｎ０鼻咽癌患者单纯分段放疗１９１例，上颈放疗剂量〉４５Ｇｙ－５０Ｇｙ，和〉５０Ｇｙ－５９Ｇｙ的颈淋巴结复发率在ＣＴ示颈动脉鞘区阳性者差异显著（Ｐ〈０．０１）；阴性者差异不显著。全组上颈放疗剂量〉５０－５９Ｇｙ和〉６０Ｇｙ者颈淋巴结复发率无显著差异，只行上半颈和行全颈预防放疗的颈淋巴结复发率亦无显著差异。因此，Ｎ０鼻咽癌患者颈部放疗剂量〉５０Ｇｙ