Amifostine is a Potent Radioprotector of Salivary Glands in Radioiodine Therapy Structural and Ultrastructural Findings*

Background and Purpose:   

Salivary gland impairment following high-dose radioiodine treatment is well recognized. Since differentiated thyroid cancer has a good prognosis, reduction of long-term side effects is important. This study investigates the radioprotective effects of amifostine in salivary glands of rabbits receiving high-dose radioiodine therapy so as to obtain deeper insight in changes on the cellular and ultrastructural level.     

涎腺肌上皮瘤的CT表现

目的分析涎腺肌上皮瘤(myoepithelioma,ME)的CT表现,以提高对该病的认识。资料与方法回顾性分析12例经病理证实的涎腺ME的CT表现并复习相关文献。所有病例均行CT平扫,其中9例行增强扫描。结果 12例肿瘤中发生于大涎腺9例(其中腮腺6例,颌下腺3例),小涎腺3例(鼻腔、硬腭、咽旁间隙各1例)。8例肿块边界清楚,4例肿块边界不清,其中1例发生于硬腭伴有骨质吸收破坏。平扫肿块多呈中等软组织密度,9例密度不均,3例密度均匀。增强扫描不均匀强化7例,肿块内可见结节样强化,囊变区不强化,均匀强化1例,1例位于硬腭病灶强化不明显。结论涎腺ME的CT表现具有一定特点,能为临床诊断和选择手术方式提供帮助。     

改良半定量唾液腺动态显像分析腮腺功能方法初探

目的:建立改良99mTcO4-唾液腺动态显像方法和腮腺半定量功能指标.材料和方法:对30例正常人和44例干燥综合征患者分别进行30min99mTcO4-动态显像,于第15min时舌下含服维生素C(Vit.C)o.1g,利用计算机感兴趣区(ROI)技术和自编软件获得腮腺时间-放射性曲线和各功能参数,比较两组各功能指标.结果:74例受检者顺利完成检查.患者和正常对照组双侧腮腺第15min摄取指数、相对摄取指数及排泄分数差异明显(P<0.05).结论:改良99mTcO4-唾液腺动态显像省时,其功能指标可直观、客观反映腮腺功能,值得进一步推广.     

Significance of Salivary Gland Radioiodine Retention on Post-ablation 131I Scintigraphy as a Predictor of Salivary Gland Dysfunction in Patients with Differentiated Thyroid Carcinoma

Purpose

We investigated whether ¹³¹I whole-body scintigraphy could predict functional changes in salivary glands after radioiodine therapy.

Methods

We evaluated 90 patients who received initial high-dose (≥3.7 GBq) radioiodine therapy after total thyroidectomy. All patients underwent diagnostic (DWS) and post-ablation (TWS) ¹³¹I whole-body scintigraphy. Visual assessment of salivary radioiodine retention on DWS and TWS was used to divide the patients into two types of groups: a DWS+ or DWS- group and a TWS+ or TWS- group. Salivary gland scintigraphy was also performed before DWS and at the first follow-up visit. Peak uptake and %washout were calculated in ROIs of each gland. Functional changes (Δuptake or Δwashout) of salivary glands after radioiodine therapy were compared between the two groups.

Results

Both peak uptake and the %washout of the parotid glands were significantly lower after radioiodine therapy (all p values <0.001), whereas only the %washout were significantly reduced in the submandibular glands (all p values <0.05). For the parotid glands, the TWS+ group showed larger Δuptake and Δwashout after radioiodine therapy than did the TWS- group (all p values <0.01). In contrast, the Δuptake and Δwashout of the submandibular glands did not significantly differ between the TWS+ and TWS- groups (all p values >0.05). Likewise, no differences in Δuptake or Δwashout were apparent between the DWS+ and DWS- groups in either the parotid or submandibular glands (all p values >0.05).

Conclusion

Salivary gland radioiodine retention on post-ablation ¹³¹I scintigraphy is a good predictor of functional impairment of the parotid glands after high-dose radioiodine therapy.     

口内酸刺激对主涎腺ADC值影响的初步观察

目的 探讨在口内酸刺激不同保持时间下主涎腺表观扩散系数(ADC)值的变化规律及差异.方法 对18名涎腺功能正常的志愿者,先于静息状态下行1次腮腺、颌下腺和舌下腺DW-MRI扫描作为基准.然后,在相邻的两天中的同一时间,向受试者口内滴注5 ml柠檬汁后采用两种不同的刺激方式:一天口内含10 s,另一天口内含2 min后吞咽,然后行扩散加权磁共振成像(DW-MRI)重复扫描各10次.两种刺激方式的先后顺序采取随机原则.分析不同保持时间组酸刺激前后主涎腺ADC值变化曲线的特点及差异,比较两组刺激后最大ADC值、刺激后最大ADC值增加率(IR)以及峰值时间(Tmax)的差别.结果 两种不同刺激保持时间组各涎腺平均ADC值均在刺激后第一次扫描时(30 s)达到峰值,之后呈缓慢波动下降的单相变化趋势.柠檬汁含10 s组颌下腺Tmax为(523±415)ms,显著晚于含2 min组的(243±265) ms(￡=-3.168,P=0.006).柠檬汁含10 s组刺激后腮腺、颌下腺与舌下腺的最大ADC值分别为(1.05±0.06) ×10-3mm2/s、(1.16±0.07)×10-3mm2/s与(1.11 ±0.06)×10-3mm2/s,均显著低于含2 min组的(1.09 ±0.04)×10-3mm2/s、(1.24 ±0.09)×10-3mm2/s与(1.28±0.18)×10-3mm2/s(腮腺t=-3.393,P=0.003;颌下腺t=-6.655,P=0.000;舌下腺t=-3.665,P=0.002).两组刺激后各涎腺最大ADC值均显著高于刺激前(P＜0.01).柠檬汁含10 s组刺激后颌下腺最大ADC值IR为(7.94±4.53)％,显著低于含2 min组的(14.26 ±8.94)％(t=-4.821,P=0.000).结论 柠檬汁味觉刺激后DW-MRI可以显示刺激不同保持时间下各涎腺ADC值变化规律的差异,是评价涎腺分泌功能的合适方法之一.     

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.     

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 consentient 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. Hintergrund: Welchen Einfluss hat das bewusste Aussparen der kontralateralen großen Speicheldrüsen (Glandulae parotis, submandibulares und sublinguales) bei radikaler Strahlentherapie von HNO-Tumoren auf das Milieu der Mundhöhle (Speichel-pH, -Pufferkapazität, -flussrate und Streptococcus-mutans-Kolonisation)? Patienten und Methoden: 20 konsekutive, zustimmende Patienten mit HNO-Tumoren wurden einmal vor, wöchentlich während und 6 Wochen nach Abschluss der Radiotherapie bezüglich Speichelflussrate, pH-Wert, Pufferkapazität des Speichels sowie Kolonisierung mit Streptococus mutans untersucht. Bei 13 Patienten waren alle großen Speicheldrüsen im behandelten Volumen eingeschlossen, bei sieben Patienten sparte die Feldanordnung bewusst die kontralateralen Speicheldrüsen aus. Ergebnisse: Die stimulierbare Speichelmenge nimmt schon während der 1. Woche der Radiotherapie ab, sinkt exponentiell zur Dosis und reduziert sich in den Wochen nach Abschluss der Therapie weiter. Der Effekt ist bei Patienten mit Schonung der kontralateralen großen Speicheldrüsen deutlich geringer ausgeprägt. Die Mehrzahl der Patienten mit einseitiger Schonung hält den Ausgangswert der Pufferkapazität, während alle Patienten mit Einschluss aller großen Speicheldrüsen schon bei Dosen ab 20 Gy erheblich an Pufferkapazität in der Mundhöhle ohne Zeichen der Erholung nach Abschluss der Therapie verlieren. Bei einseitiger Schonung bleibt der Speichel-pH immer basisch; bei beidseitig bestrahlten Patienten sinkt der pH während und nach der Radiotherapie von 7,3 Mittelwert auf 5,8 ab. Die Kolonisierung mit Streptococcus mutans variiert in beiden Patientengruppen während der Radiotherapie wenig; sie ist bei beidseitig bestrahlten Patienten nach Abschluss der Therapie höher als bei Patienten mit Schonung einer Parotis. Schlussfolgerungen: Die bewusste Anordnung der Felder zur Schonung der kontralateralen großen Speicheldrüsen bei Radiotherapie von HNO-Tumoren hat einen signifikanten Effekt auf das Milieu der Mundhöhle: Die stimulierbare Speichelmenge bleibt größer, die Pufferkapazität hält den Ausgangswert, der Speichel-pH bleibt basisch und die Kolonisierung mit Streptococcus mutans bleibt auf dem Niveau des Behandlungsbeginnes.     

Analysis of Iodine Content in Salts and Korean Sauces for Low-Iodine Diet Education in Korean Patients with Thyroid Cancer Preparing for Radioiodine Therapy

Purpose

A low-iodine diet is necessary in patients about to undergo radioiodine therapy for thyroid cancer to decrease the competitive absorption of ingested nonradioactive iodine. This study aimed to assess the iodine concentrations in salts and basic Korean sauces, and to provide fundamental data for guidelines on a low-iodine diet before radioiodine therapy.

Methods

The iodine contents of refined salts, solar sea salts, fish sauces, and commonly used Korean sauces with added refined salt were determined by ICP-MS.

Results

The iodine content of refined salts was found to be very low (0.033 ± 0.05 μg/100 g) compared with that of solar sea salts (434 ± 73.6 μg/100 g). The iodine contents of Korean soy sauce, Korean soybean paste, Gochujang seasoned with refined salt were also very low (0.010, 0.044, 0.002 μg/100 g, respectively). However, the mean iodine contents of the shrimp and fish Jeots analyzed in this study were found to be 41.3?±?4.2 and 24.8?±?4.5 μg/100 g, respectively.

Conclusion

This study is the first to investigate the iodine contents of the salts and basic sauces used in Korea. The results show that refined salts and Korean traditional sauces seasoned with them can be safely used in low-iodine diets before radioiodine therapy.

     

Radioiodine treatment of hyperthyroidism using a simplified dosimetric approach. Clinical results

PURPOSE: To evaluate the clinical effectiveness of a simplified dosimetric approach to the iodine-131 treatment of hyperthyroidism due to Graves' disease or uninodular and multinodular toxic goiter. MATERIAL AND METHODS: We enrolled 189 patients with biochemically confirmed hyperthyroidism and performed thyroid ultrasonography and scintigraphy obtaining the diagnosis of Graves' disease in 43 patients, uninodular toxic goiter in 57 patients and multinodular toxic goiter in 89 patients. In 28 patients we found cold thyroid nodules and performed fine-needle aspiration with negative cytology for thyroid malignancy in all cases. Antithyroid drugs were stopped 5 days till radioiodine administration and, if necessary, restored 15 days after the treatment. Radioiodine uptake test was performed in all patients and therapeutic activity calculated to obtain a minimal activity of 185 MBq in the thyroid 24 hours after administration. The minimal activity was adjusted based on clinical, biochemical and imaging data to obtain a maximal activity of 370 MBq after 24 hours. RESULTS: Biochemical and clinical tests were scheduled at 3 and 12 months posttreatment and thyroxine treatment was started when hypothyroidism occurred. In Graves' disease patients a mean activity of 370 MBq (distribution 259-555 MBq) was administered. Three months after treatment and at least 15 days after methimazole discontinuation 32 of 43 (74%) patients were hypothyroid, 5 of 43 (11%) euthyroid and 6 of 43 (15%) hyperthyroid. Three of the latter were immediately submitted to a new radioiodine administration while 32 hypothyroid patients received thyroxine treatment. One year after the radioiodine treatment no patient had hyperthyroidism; 38 of 43 (89%) were on a replacement treatment while 5 (11%) remained euthyroid. In uni- and multinodular toxic goiter a mean activity of 444 MBq (distribution 259-555 MBq) was administered. Three months posttreatment 134 of 146 (92%) patients were euthyroid and 12 of 146 (8%) patients hyperthyroid. Two patients were immediately submitted to a new radioiodine administration. One year posttreatment 142 of 146 (97%) patients were euthyroid while only 4 of 146 (3%) patients showed TSH levels above the normal range. Only 2 of them required thyroxine treatment. CONCLUSIONS: The simplified dosimetric method illustrated in our paper is very effective in clinical practice because it permits to avoid resorting to sophisticated but also imprecise quantitative methods. Hypothyroidism should not be considered as a major collateral effect of radioiodine treatment, particularly in Graves' disease. In fact, the pathogenesis of the disease requires an ablative treatment with both surgery and radioidine treatment and the control of hyperthyroidism and the prevention of relapse are the major clinical targets. Vice versa, hypothyroidism was very uncommon in uni- and multinodular toxic goiter when our dosimetric approach was applied.     

Injection of Botulinum Toxin for Preventing Salivary Gland Toxicity after PSMA Radioligand Therapy: an Empirical Proof of a Promising Concept

The dose-limiting salivary gland toxicity of ²²⁵Ac-labelled PSMA for treatment of metastatic, castration-resistant prostate cancer remains unresolved. Suppressing the metabolism of the gland by intraparenchymal injections of botulinum toxin appears to be a promising method to reduce off-target uptake. A ⁶⁸Ga-PSMA PET/CT scan performed 45 days after injection of 80 units of botulinum toxin A into the right parotid gland in a 63-year-old patient showed a decrease in the SUVmean in the right parotid gland of up to 64% as compared with baseline. This approach could be a significant breakthrough for radioprotection of the salivary glands during PSMA radioligand therapy.     

Comparison of the Influence on the Liver Function Between Thyroid Hormone Withdrawal and rh-TSH Before High-Dose Radioiodine Therapy in Patients with Well-Differentiated Thyroid Cancer

Purpose

An elevated thyroid stimulating hormone level (TSH) is essential to stimulate the uptake of radioiodine into thyroid remnants and metastases of thyroid cancer when a patient undergoes high-dose radioiodine therapy. Nowadays, recombinant human thyroid stimulating hormone (rh-TSH) is increasingly used instead of the classic method of thyroid hormone withdrawal (THW). However, beyond the therapeutic effects, clinical differences between the two methods have not yet been clearly demonstrated. The aim of this work was to investigate the effects of the two methods, especially on liver function.

Methods

We identified 143 evaluable patients who were further divided into two groups: THW and rh-TSH. We first reviewed the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, which were measured during the admission period for total thyroidectomy. We called these liver enzyme levels “base AST” and “base ALT.” We also assessed other chemistry profiles, including AST, ALT, total cholesterol, LDL cholesterol, alkaline phosphatase (ALP), total bilirubin (TB), and triglyceride (TG), which were measured on admission day for high-dose radioiodine therapy. We called these liver enzyme levels “follow-up AST” and “follow-up ALT.” We compared the changes in base and follow-up liver enzyme levels and the other chemistry profiles between the two groups.

Results

The base AST and base ALT levels of the two groups were within normal range, and there was no significant difference between the two groups. In contrast to these base liver enzyme levels, follow-up liver enzyme levels between the two groups showed significant differences. Patients in the THW group had higher follow-up AST and ALT levels than did the rh-TSH group. Patients in the THW group also had higher levels of total cholesterol and LDL cholesterol than did the patients in the rh-TSH group. However there were no statistically significant differences in ALP, total bilirubin, and triglyceride levels between the two groups.

Conclusions

In this retrospective analysis of liver function, the use of rh-TSH for high-dose radioiodine therapy had less of an effect on liver function and cholesterol levels than dose thyroid hormone withdrawal. This suggests that rh-TSH can be used effectively and safely especially for patients with metabolic syndrome.     

CpG Oligodeoxynucleotides Enhance the Activities of CD8+ Cytotoxic T-Lymphocytes Generated by Combined hMUC1 Vaccination and hNIS Radioiodine Gene Therapy

Purpose

The authors evaluated whether the cytotoxicity of CD8+CTLs generated by combined hMUC1 vaccination and hNIS radioiodine gene therapy was enhanced in the presence of CpG in an established tumor model.

Methods

CMNF cells (CT26 cells expressing hMUC1, hNIS and Firefly luciferase) were transplanted into BALB/c mice. Four and 10 days later, tumor-bearing mice were immunized intramuscularly with pcDNA3.1 or pcDNA-hMUC1 or pcDNA-hMUC1+CpG, and subsequently administered PBS or ¹³¹I [five groups (seven mice/group): referred to as the pcDNA3.1+PBS, phMUC1+PBS, pcDNA3.1+¹³¹I, phMUC1+¹³¹I, and phMUC1+¹³¹I+CpG groups]. The number of CD8+IFNr+ T cells of splenocytes as well as the number of CD8+IFNr+ T cells of splenocytes re-stimulated with CD11c+ cells was determined using FACS analysis. The activities of cytotoxic T cells (CTLs) from splenocytes were investigated.

Results

Marked tumor growth inhibition was observed in the phMUC1+¹³¹I and phMUC1+¹³¹I+CpG groups, but not in the other three single therapy groups. Particularly the number of CD8+IFN-γ+ T cells of splenocytes was more increased in the phMUC1+¹³¹I+CpG group than in the phMUC1+¹³¹I group. The number of CD8+IFN-γ+ T cells of splenocytes stimulated with CD11c+ cells was the most enhanced in the phMUC1+¹³¹I+CpG group among the five groups. Concurrently, the activities of hMUC1-associated CTLs obtained from splenocytes in the phMUC1+¹³¹I+CpG group were significantly greater than in the other four groups (pcDNA+PBS, phMUC1+PBS, pcDNA+¹³¹I, phMUC1+¹³¹I, and phMUC1+¹³¹I+CpG, 16 ± 2%, 20 ± 1%, 30 ± 2%, 60 ± 2%, and 87 ± 2%, respectively, P < 0.01).

Conclusion

Our data suggest that adjuvant CpG ODNs can increase the killing activities of CTLs generated by combined hMUC1 DNA vaccination and hNIS radioiodine gene therapy.     

Radioiodine uptake by metastatic nonthyroidal adenocarcinoma of the lung in a patient with papillary thyroid carcinoma

A 49-year-old woman with a history of a hysterectomy for carcinoma of the cervix and papillary thyroid carcinoma showed multiple pulmonary metastases on chest radiography. An I-131 scan revealed multiple areas of increased uptake in the chest. These lesions were found to be metastatic cervical adenocarcinoma. The radioiodine uptake by the metastatic cervical adenocarcinoma of the lungs occurred in the presence of normal thyroid imaging in a patient with a thyroid nodule and papillary thyroid carcinoma.