涎腺干细胞在放射性口干症中的应用及研究进展

放射治疗是头颈部肿瘤的主要治疗方法之一,但有引起放射性口干症的可能。目前放射性口干症尚无较好的防治方法,近年来的研究发现,涎腺干细胞主要集中分布在涎腺较大的排泄管上,其可对放射后损伤的涎腺结构和功能起到修复作用,若能在放疗中有效保护涎腺干细胞,则有可能减轻口干症状。另外,应用涎腺干细胞移植技术修复受损的涎腺已在动物实验中得到验证。若能将涎腺干细胞科学有效地应用于临床,则有望改善病人放疗后口干症状,提高生活质量。     

环戊硫酮治疗放射性口干症的临床研究

头颈肿瘤在放射治疗中占有较大比例 ,该区域肿瘤原发部位及其淋巴引流区往往与涎腺组织紧密相邻 ,因此 ,整个或部分涎腺需包括在照射野内 ,从而造成急性或后期涎腺功能障碍。其症状主要是口干及其继发的味觉丧失、龋齿和口腔粘膜溃疡等 ,严重影响口腔健康及营养的供给 ,降低了患者的生存质量。我们从 1998年 9月～ 1999年 12月间进行了随机分组对照试验 ,用环戊硫酮和安慰剂治疗头颈部的肿瘤患者放疗所致口干症各 2 0例 ,现将结果报告如下。一、材料和方法1 病例选择及用药方法住院或门诊病人因头颈部肿瘤放疗后引起口干症的患者 ,无严重心…     

头颈部放疗后软组织损伤的CT表现

目的 :本文旨在观察和探讨头颈部肿瘤放疗后软组织损伤的CT表现 ,以提高对头颈部放射性损伤的影像学认识。方法 :对头颈部恶性肿瘤放疗后 70例作CT扫描观察 ,计 13 3次扫描 ,扫描 1次 3 8例 ,2次 15例 ,3次以上 17例。观察时间分为放疗后近期 ( 6个月以内 )、中期 ( 6～ 12个月 )和远期 ( 12个月以上 )。放疗剂量为 40～ 72Gy(单程放疗 )、14 0Gy(二程及二程以上放疗 )。全部病例均有放疗前CT图像对照。结果 :CT所见包括皮下脂肪层变薄 2 6例 ,皮肤增厚15例 ,皮肤凹陷 2 6例 ,肌肉萎缩 19例 ,颈深筋膜增厚 15例 ,皮下纤维性增生 18例 ,涎腺萎缩 19例 ,复发性肿瘤 18例。结论 :CT对头颈部软组织放射性损伤的表现和程度的判断是准确的 ,能为临床治疗提供参考依据     

康复新液联合美皮康泡沫敷料治疗头颈部肿瘤放疗后的皮肤损伤

头颈部肿瘤由于放疗时间长、剂量大,引起放射性皮肤损伤发生率高,轻者皮肤脱屑、渗液,3~4级放射性皮肤损伤属于较重的皮肤损伤^[1],既增加患者痛苦,又影响疗效。因此,及时有效地治疗3级以上放射性皮肤损伤是首要问题。对头颈部肿瘤放疗致皮肤损伤采用康复新液、美皮康泡沫敷料治疗,取得满意效果,现报道如下。     

头颈部肿瘤急性放射性皮肤损伤的护理

放射性皮肤损伤是头颈部肿瘤放射治疗最常见的并发症，它与局部毛囊、皮脂腺、汗腺萎缩以及血管通透性改变有关。轻者有轻微的皮肤烧灼感、刺痛、瘙痒等不适，重者可能会出现皮肤糜烂、溃疡等，需要中断治疗，严重影响患者的生活质量及放疗疗效，延长住院时间，增加患者的经济负担。因此，做好各种预防及护理工作，使病人顺利完成放疗计划是十分重要的。现就头颈部肿瘤急性放射性皮肤损伤的护理经验介绍如下。     

头颈部肿瘤放疗相关口腔并发症和治疗

放疗是头颈部肿瘤患者常见的治疗方式。头颈部放疗常会导致口腔颌面部并发症, 因该部位组织结构复杂, 发病机制多样, 现有的治疗方案和研究进展较为局限。本文重点对最常见的放射性口腔黏膜炎、放射性唾液腺损伤及放射性龋齿进行系统总结, 回顾了现有发病机制假说、治疗及研究进展, 以期为深入研究相关病理机制和新的预防、治疗手段提供一定的参考。     

放射性龋齿相关因素研究

随着综合治疗在头颈部肿瘤放疗中的应用和病人长期生存率的提高,需要对相关并发症的治疗及病人的生存质量给予越来越多的关注.放射性龋齿是头颈部肿瘤放疗后最常见的远期损伤.对放射性龋齿形成原因、影响因素、治疗方法及预防措施进行综述,并探寻降低放射性龋齿发生率的有效方法.     

放射性龋齿相关因素研究

随着综合治疗在头颈部肿瘤放疗中的应用和病人长期生存率的提高，需要对相关并发症的治疗及病人的生存质量给予越来越多的关注。放射性龋齿是头颈部肿瘤放疗后最常见的远期损伤。对放射性龋齿形成原因、影响因素、治疗方法及预防措施进行综述，并探寻降低放射性龋齿发生率的有效方法。     

外放疗联合个体化导板辅助 125I放射性粒子植入治疗晚期头颈部鳞癌

目的：探讨外放疗联合个体化导板辅助¹²⁵I放射性粒子植入治疗无法手术的头颈部鳞癌的可行性及不良反应。 方法：对17例因全身系统疾病而无法手术的头颈部鳞癌患者进行常规分割放疗联合个体化导板辅助¹²⁵I放射性粒子植入增量放疗。外放疗总照射剂量为50 Gy,放射性粒子匹配周缘剂量（matched peripheral dose, MPD）为80~120 Gy。 结果：通过肿瘤体积变化情况和临床表现评价治疗标准,17例患者治疗总有效率达到82.4%（14/17）,1例死于大出血。主要的不良反应包括：软组织坏死、局部出血及放射性黏膜炎和皮炎等,治疗过程未发生急性并发症与严重的放射性损伤。 结论：外放疗联合个体化导板辅助¹²⁵I放射性粒子植入治疗晚期头颈部鳞癌,是一种微创、有效、安全性高的治疗方案。     

快中子治疗头颈部复发的涎腺腺样囊腺癌的近期疗效

头颈部涎腺肿瘤较为少见 ,约占头颈部肿瘤的 2 %～4% ,其中 35 %～ 5 0 %为腺样囊腺癌[1 ] 。以往治疗以手术为主 ,近来研究表明手术 常规射线放疗可提高生存率 ,但对于局部晚期或复发的患者 ,局部控制率和长期生存率仍很低。自本世纪 30年代ＲｏｂｅｒｔＳｔｏｎｅ[2 ] 率先将快中子用于恶性肿瘤的临床治疗 ,越来越多的研究机构在用快中子治疗头颈部恶性肿瘤、软组织肉瘤、骨肉瘤和局部晚期前列腺癌等方面积累了丰富的临床经验[3 ,4] 。由于快中子对于腺样囊腺癌ＲＢＥ值高达 8,是常规射线的 2 5倍 ,而对正常组织的晚期反应仅为 3～ 3 5 …     

核医学对放疗诱发的肾、脑、唾液腺等正常组织损伤的监测

放疗诱发的肾、脑、唾液腺等正常组织损伤，是肿瘤限量照射后的主要并发症。用核医学显像技术有助于放疗计划中对3个重要器官剂量效应的估算、功能损伤的早期发现和监测，从而提高放射治疗的有效性。     

Evidence for early and persistent impairment of salivary gland excretion after irradiation of head and neck tumours

Salivary gland scintigraphy with technetium-99m pertechnetate was used to follow changes in the excretion and uptake function of the major salivary glands until 1 year after irradiation. Twenty-five patients who received radiotherapy for head and neck tumours were included in the study. Seventy-nine salivary glands (39 parotid and 40 submandibular) were evaluated in relation to the average received radiation dose. Salivary gland scintigraphy was performed before and 1, 6 and 12 months after radiotherapy. For each gland the excretion response to carbachol, evaluated by calculation of the salivary excretion fraction (SEF), the cumulative gland uptake (CGU) and the absolute excreted activity (AEA) at various intervals after radiotherapy were compared with the baseline values. The excretion response decreased in 20 of 25 patients at 1 month after radiotherapy. One month after radiotherapy both SEF and AEA decreased significantly in relation to the radiation dose. These decreases in excretion parameters persisted during the follow-up period. Parotid excretion was affected significantly more than submandibular excretion. CGU values did not change significantly until 6 months after radiotherapy, but at 12 months a significant decrease related to radiation dose was observed. Xerostomia was assessed during radiotherapy and on the days of the scintigraphic tests. The incidence of xerostomia did not correspond to the effects observed in the scintigraphy studies. It is concluded that radiotherapy induces early and persistent impairment of salivary gland excretion, related to the radiation dose. This impairment is stronger in parotid glands than in submandibular glands.     

核医学对放疗诱发的肾、脑、唾液腺等正常组织损伤的监测

放疗诱发的肾、脑、唾液腺等正常组织损伤,是肿瘤限量照射后的主要并发症。用核医学显像技术有助于放疗计划中对3个重要器官剂量效应的估算、功能损伤的早期发现和监测,从而提高放射治疗的有效性。     

Salivary scintigraphy for assessing the protective effect of pilocarpine in head and neck irradiated tumours

Patients with head and neck cancers can develop salivary hypofunction after radiotherapy. The use of pilocarpine during radiotherapy treatment has been shown to be an effective treatment, although its usefulness is being discussed. The aim of this study was: (1) to determine the value of a semiquantitative scintigraphy method for measuring the uptake and excretory salivary function of patients with head and neck irradiated tumours; and (2) to study the usefulness of pilocarpine as a salivary gland protector during radiotherapy. We prospectively studied 49 patients (mean age 61 years, range 29-87 years) with head and neck cancer in need of radiotherapy. Patients were divided into two groups consecutively: group P (26 patients) received 5 mg of pilocarpine three times per day starting the day before radiation therapy, and group NP (23 patients) received radiotherapy without pilocarpine and were used as the control group. Salivary gland scintigraphy and a visual analogue scale (VAS) of mouth dryness were obtained from each patient before radiotherapy and during the first year after treatment. The most frequent finding after radiotherapy was a quick impairment in parotid and submaxillary excretion (P < 0.001). There were no statistical differences comparing the pilocarpine group against the non-pilocarpine group. Parotid and submaxillary uptake significantly decreased after radiotherapy in both groups (P < 0.001). However, a tendency to recover within the pilocarpine group was observed in both the parotids and the submaxillary glands at 12 months. No differences were found comparing the VAS results in both groups. Strikingly, VAS data did not correlate with salivary gland dysfunction observed by means of scintigraphy. In conclusion, salivary scintigraphy is a useful technique to evaluate objectively the salivary gland function of patients with head and neck irradiated tumours as well as to test the response to pilocarpine. However, despite better results on the salivary uptake at 12 months, pilocarpine did not significantly improve salivary gland function.     

Sparing of Contralateral Major Salivary Glands Has a Significant Effect on Oral Health in Patients Treated with Radical Radiotherapy of Head and Neck Tumors

BACKGROUND: Has a conscious exclusion of the contralateral major salivary glands (parotid, submandibular, and sublingual glands) a significant impact on the milieu of the oral cavity (saliva flow, pH, buffer capacity, and colonisation with Streptococcus mutans) in patients with ENT tumors receiving radical radiotherapy? PATIENTS AND METHODS: 20 consecutive consenting patients with ENT tumors were evaluated once before, weekly during, and 6 weeks after the end of treatment in regard to saliva flow, ph, buffer capacity, and colonisation with Streptococcus mutans. In 13 patients the major salivary glands on both sides were included in the treated volume, in seven patients the treatment portals excluded consciously the contralateral major salivary glands. RESULTS: The stimulated saliva flow decreases already during the 1st week of radiotherapy, the decrease follows the dose exponentially; the saliva flow is further reduced in the weeks after the end of treatment. The effect is less pronounced in patients with sparing of contralateral major salivary glands. The majority of patients with unilateral sparing of the major salivary glands retain the baseline value of buffer capacity, whereas buffer capacity of all patients with inclusion of all major salivary glands is markedly reduced with 20 Gy already, without signs of recovery when treatment has stopped. With unilateral salivary gland sparing the pH always remains basic, in bilaterally irradiated patients the pH changes from a mean of 7.3 to 5.8 during treatment. The colonisation with Streptococcus mutans varies little in both groups during the radiotherapy; after the end of therapy, it is higher in bilaterally irradiated patients. CONCLUSIONS: The conscious arrangement of irradiation portals in order to spare contralateral major salivary glands in patients with radical radiotherapy of ENT tumors has a significant influence on the oral environment: the stimulated saliva flow is higher, the buffer capacity retains the baseline value, the saliva pH remains basic, and the colonisation with Streptococcus mutans is reduced.     

Semi-quantitative assessment of salivary gland function in patients with differentiated thyroid carcinoma after radioiodine-131 treatment

Sialadenitis and xerostomia are well-known side effects of high-dose radioactive iodine ((131)Iota) treatment in patients with differentiated thyroid carcinoma (DTC). This study was undertaken to determine salivary gland function semi-quantitatively in patients with DTC given (131)I for the treatment of the thyroid remnant and/or metastases. Thirty-six patients, 11 males and 25 females, mean age 53.5 years, range 22-73 years, were studied. Scintigraphy of the salivary glands was performed with (99m)Tc-pertechnetate and the salivary excretion fraction (SEF) of the parotid and the submandibular glands was calculated as a measure of their function. Measurements were performed before (131)I treatment as a baseline study, and three weeks and three months later. The patients were clinically evaluated by a standardized subjective questionnaire. Results were as follows: Mean SEF at three weeks and three months after (131)I treatment was reduced as compared to baseline measurements. The total mean baseline measurements, those of three weeks and those of three months later were: 54.9%, 47.2% and 46% respectively; P<0.05 for both measurements (Table 1). The SEF decrease of the parotid glands was greater than that of the submandibular glands (P<0.05 as compared for both salivary glands before and three weeks and three months after (131)I treatment). This confirmed the higher radiosensitivity of the parotid glands as compared to the submandibular glands. In 12 patients (33%) there was no significant decrease of SEF in the salivary glands after (131)I treatment. The relation between the decrease of SEF after three weeks and after three months and the dose of (131)I administered, was for the right and left submandibular glands significant (P=0.016 and P=0.002), while for the parotid glands it was insignificant (P=0.22 and P=0.27 respectively) (Table 4). Reduction of SEF in the parotid glands three months after (131)I treatment was greater than after three weeks. This difference, as regards the submandibular glands, was not significant. Our results show that high dose (131)I treatment in DTC patients induces a significant effect on salivary gland function, which is dose-related in the submandibular glands, and more prominent in the parotid glands.     

Functional evaluation with intravoxel incoherent motion echo-planar MRI in irradiated salivary glands: a correlative study with salivary gland scintigraphy

The purpose of this study was to determine the relationship between the apparent diffusion coefficient (ADC) measured on intravoxel incoherent motion (IVIM) echo-planar magnetic resonance imaging (MRI) and salivary gland function. Twenty-one patients with head and neck malignancies underwent MRI and salivary gland scintigraphy before and after radiotherapy. Based on the scintigraphic results, each major salivary gland was classified into two groups (dysfunctional and functional) and ADCs measured on IVIM MRI were compared between the two groups. Furthermore, the relationship of ADC to scintigraphic parameters, maximum accumulation (MA), and the uptake ratio (UR), were analyzed. ADCs of the dysfunctional group decreased significantly after radiotherapy (P <.01), whereas those of the functional group showed no significant change. Furthermore, positive correlations were found between the ADC ratio and both MA (P <.005) and UR (P <.001). ADC measurement on IVIM echo-planar MRI is a potentially useful means of evaluating salivary gland function.     

Lymphoepithelioma-like carcinoma of salivary glands: treatment results and failure patterns

The purpose of this study was to evaluate the treatment results and failure patterns of lymphoepithelioma-like carcinoma (LELC) of salivary glands. From June 1987 to May 2001, nine patients with LELC of salivary glands were treated at our hospital. One patient was excluded due to the loss of clinical follow-up after surgery. For the remaining eight patients, the primary tumour sites were parotid glands (4 patients), submandibular glands (3), and the minor salivary glands in right cheek (1), respectively. Seven patients underwent surgical treatment and post-operative radiotherapy, while the other one patient was treated with surgery only. The total radiation dose to the salivary tumour bed ranged from 39.6 Gy to 67.6 Gy (mean dose: 58.3 Gy and median dose: 59 Gy). The treatment results and failure patterns were analysed. The survival time ranged from 21.4 months to 145.2 months (mean: 69.1 months, median: 54.5 months). At the end of follow-up, six patients were still alive and two died. One patient died of distant metastases 21.5 months after the surgical treatment of LELC. The other case died of intercurrent disease (pontine haemorrhage) 53 months after surgery. No patient had local or regional failure after the treatments. Distant failure was noted in two patients. The patients with LELC of salivary glands were shown to have favourable prognoses. No local or regional failure was noted. However, distant failure developed in two patients. The risk of distant metastasis should be carefully monitored, especially for those patients with more advanced neck node involvement.     

Tubarial salivary gland sparing with proton therapy

The recently identified bilateral macroscopic tubarial salivary glands present a potential opportunity for further toxicity mitigation for patients receiving head and neck radiotherapy. Here, we show superior dosimetric sparing of the tubarial salivary glands with proton radiation therapy (PRT) compared to intensity-modulated radiotherapy (IMRT) for patients treated postoperatively for human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). This was a retrospective, single institutional study of all patients treated with adjuvant PRT for HPV-associated OPSCC from 2015 to 2019. Each patient had a treatment-approved, equivalent IMRT plan to serve as a reference. The main end point was dose delivered to the tubarial salivary glands by modality, assessed via a 2-tailed, paired t-test. We also report disease outcomes for the entire cohort, via the Kaplan-Meier method. Sixty-four patients were identified. The mean RT dose to the tubarial salivary glands was 23.6 Gy (95% confidence interval (CI) 21.7 to 25.5) and 30.4 Gy (28.6 to 32.2) for PRT and IMRT plans (p < 0.0001), respectively. With a median follow-up of 25.2 months, the two-year locoregional control, progression-free survival and overall survival were 97.8% (95% CI 85.6% to 99.7%), 94.1% (82.8% to 98.1%) and 98.1% (87.4% to 99.7%), respectively. Our study suggests that meaningful normal tissue sparing of the recently identified tubarial salivary glands is achievable with PRT. The apparent gains with PRT did not impact disease outcomes, with only 1 observed locoregional recurrence (0 local, 1 regional). Further studies are warranted to explore the impact of the improved dosimetric sparing of the tubarial salivary glands conveyed by PRT on patient toxicity and quality of life.