Limited Clinical Value of Periablative Changes of Serum Markers in the Prediction of Biochemical Remission in Patients with Papillary Thyroid Cancer

Purpose

Remnant thyroid ablation and 1-year stimulated thyroglobulin (sTg) measurement are recommended for those who have undergone total thyroidectomy for differentiated thyroid cancer. The serum Tg kinetics in such patients are still unclear. This study was designed to evaluate whether the periablative change in serum markers can predict biochemical remission in papillary thyroid cancer (PTC) patients.

Methods

We reviewed the medical records of 185 patients who were given high-dose radioactive iodine ablation therapy from January 2006 to December 2008. Serum Tg, TSH, and anti-Tg antibody (TgAb) were measured on the day and the following 10th day of radioactive iodine administration. We defined preablative sTg as Tg-1, postablative Tg measured on the 10th day of ablation as Tg-2, and the 1-year sTg as Tg-3. ΔTg means Tg2-Tg1. The same definition was applied to TgAb.

Results

A biochemical remission defined as Tg-3 < 2 ng/ml was achieved in 144 patients. Among the patients who achieved biochemical remission, PTC recurred in six during a median follow-up of 54 months. Tg-1 < 3.3 ng/ml (p < 0.0001) predicted biochemical remission. Neither the ΔTg nor ΔTgAb was useful for predicting biochemical remission. On the evaluation of recurrence after biochemical remission, Tg-1 > 5.32 (p < 0.0001) and Tg-3 > 2.9 (p = 0.01) were proven to be statistically significant cutoff values for predicting recurrence. The ΔTg and ΔTgAb were not able to predict recurrence.

Conclusion

For the prediction of biochemical remission or recurrence after biochemical remission, preablative sTg was demonstrated to be a statistically significant serum marker. However, short-term changes in biochemical markers including Tg and TgAb around the day of ablation could not provide useful clinical information about biochemical remission or disease recurrence. In conclusion, 1-year sTg measurement cannot be omitted with short-term change.     

Radioiodine Scan Index: A Simplified,Quantitative Treatment Response Parameter for Metastatic Thyroid Carcinoma

Purpose

We aimed to develop and validate a simplified, novel quantification method for radioiodine whole-body scans (WBSs) as a predictor for the treatment response in differentiated thyroid carcinoma (DTC) patients with distant metastasis.

Methods

We retrospectively reviewed serial WBSs after radioiodine treatment from 2008 to 2011 in patients with metastatic DTC. For standardization of TSH simulation, only a subset of patients whose TSH level was fully enhanced (TSH > 80 mU/l) was enrolled. The radioiodine scan index (RSI) was calculated by the ratio of tumor-to-brain uptake. We compared correlations between the RSI and TSH-stimulated serum thyroglobulin (TSH_s_Tg) level and between the RSI and Tg reduction rate of consecutive radioiodine treatments.

Results

A total of 30 rounds of radioiodine treatment for 15 patients were eligible. Tumor histology was 11 papillary and 4 follicular subtypes. The TSH_s_Tg level was mean 980 ng/ml (range, 0.5–11,244). The Tg reduction rate after treatment was a mean of −7 % (range, −90 %–210 %). Mean RSI was 3.02 (range, 0.40–10.97). RSI was positively correlated with the TSH_s_Tg level (R² = 0.3084, p = 0.001) and negatively correlated with the Tg reduction rate (R² = 0.2993, p = 0.037). The regression equation to predict treatment response was as follows: Tg reduction rate = −14.581 × RSI + 51.183.

Conclusions

Use of the radioiodine scan index derived from conventional WBS is feasible to reflect the serum Tg level in patients with metastatic DTC, and it may be useful for predicting the biologic treatment response after radioiodine treatment.     

Predictive factors for the outcomes of initial I-131 low-dose ablation therapy to Japanese patients with differentiated thyroid cancer

Objective

To identify prognostic factors associated with a low-iodine diet (LID) and the amount of remnant thyroid tissue in Japanese patients with differentiated thyroid cancer (DTC) who received initial I-131 remnant ablation (RAI) using a fixed low dose of I-131 (1110 MBq).

Patients and methods

In this prospective study, we enrolled 45 patients. Patients were classified into a self-managed LID group and a strict LID group. We measured the urinary iodine concentration on the day of RAI after patients consumed LID for 2 weeks. Thyroid-stimulating hormone-induced thyroglobulin (Tg) levels and I-131 uptake by the remnant thyroid tissue were also evaluated. A response-evaluation whole-body scan (WBS) was performed 6–8 months after RAI to determine the outcome of the therapy.

Results

Post-LID urinary iodine levels of the strict LID group tended to be lower than those of the self-managed LID group. Twenty-five cases (56%) showed absence of uptake, whereas 20 cases (44%) showed residual uptake on the response-evaluation WBS. There were no significant differences between “absence” and “residual” groups in urinary iodine concentrations and Tg levels (p?=?0.253 and p?=?0.234, respectively). However, significant differences were observed in I-131 uptake by the thyroid bed (p?=?0.035).

Conclusions

For patients following the current Japanese method of a 2-week LID, the urinary iodine concentration was not a predictive factor for the successful outcome of RAI. In contrast, low I-131 uptake by the thyroid bed, revealed by the scintigram after RAI, may serve as a favorable predictive factor.

     

Analysis of Clinical Factors for the Determination of Optimal Serum Level of Thyrotropin After Recombinant Human Thyroid-Stimulating Hormone Administration

Purpose

To determine the optimal levels of thyroid-stimulating hormone (TSH) levels after administration of recombinant human TSH (rhTSH) to patients with differentiated thyroid cancer (DTC), we have analyzed the clinical parameters that affected the degree of the increase in serum levels of TSH.

Methods

We retrospectively analyzed 276 patients with differentiated thyroid cancer (DTC), post-thyroidectomy and remnant ablation. Pearson’s correlation coefficient test was used to evaluate the correlation between serum levels of TSH after rhTSH stimulation and various clinical factors, including age, sex, height, weight, body mass index (BMI), body surface area (BSA), serum blood urea nitrogen, creatinine, and estimated glomerular filtration rate (GFR). Linear regression analysis was used to determine the predictors of the degree of increase in serum TSH level after rhTSH stimulation.

Results

After the rhTSH injections, all subjects achieved TSH levels of >30 μU/mL, with a mean of 203.8 ± 83.4 μU/mL. On univariate analysis, age (r = 0.255) and serum creatinine (r = 0.169) level were positive predictors for higher levels of serum TSH after rhTSH stimulation, while weight (r = –0.239), BMI (r = –0.223), BSA (r = –0.217), and estimated GFR (r = –0.199) were negative predictors. Multiple linear regression analysis revealed that serum creatinine was the most powerful independent predictor for serum levels of TSH, followed by age, BSA, and BMI.

Conclusions

An increment in serum TSH after rhTSH stimulation was significantly affected by age, BSA, BMI, and creatinine, with creatinine being the most powerful predictor. By understanding the difference in the increased levels of TSH in various subjects, their dose of rhTSH can be adjusted during scheduling for radioiodine ablation, or during follow-up (recurrence surveillance) after surgery and ablation.     

Clinical Significance of Diffuse Intrathoracic Uptake on Post-Therapy I-131 Scans in Thyroid Cancer Patients

Purpose

The purpose of this study was to identify the frequency and possible cause of diffuse intrathoracic uptake on post-therapy I-131 scans in thyroid cancer patients.

Methods

We retrospectively reviewed 781 post-therapy scans of 755 thyroid cancer patients who underwent total thyroidectomy and radioactive iodine therapy between January and December 2010. Diffuse intrathoracic uptake on post-therapy scans was examined, and clinical patient characteristics including sex, age, regimen for thyroid-stimulating hormone (TSH) stimulation (thyroid hormone withdrawal or recombinant human TSH injection), TSH, thyroglobulin (Tg) and anti-thyroglobulin antibody (anti-Tg Ab) levels, therapeutic dose of radioactive iodine therapy and prior history of radioactive iodine therapy were recorded.Scan findings were correlated with chest CT, chest radiographs, laboratory tests and/or clinical status. Diffuse intrathoracic uptake without evidence of pathologic condition was categorized as indeterminate. The association between clinical characteristics and intrathoracic uptake were analyzed for negative intrathoracic uptake and indeterminate uptake groups.

Results

Diffuse intrathoracic uptake on post-therapy scans was demonstrated in 39 out of 755 (5.2 %) patients, among which 3 were confirmed as lung metastasis. The 14 patients that showed high Tg or anti-Tg Ab levels were considered to be at risk of having undetected micrometastasis on other imaging modalities. The remaining 22 were indeterminate (2.9 %).Upon comparison of negative intrathoracic uptake and indeterminate uptake groups, TSH stimulation by thyroid hormone withdrawal was shown to be significantly correlated with diffuse intrathoracic uptake (p < 0.05).

Conclusion

The frequency of diffuse intrathoracic uptake on post-therapy scans was 5.2 % and could be seen in thyroid cancer patients with underlying lung metastasis as well as those without definite pathologic condition. In the latter, there was a higher frequency for diffusely increased intrathoracic uptake in those who underwent thyroid hormone withdrawal rather than recombinant human TSH injection.     

Evaluation of lung cancer by enhanced dual-energy CT: association between three-dimensional iodine concentration and tumour differentiation

Objective:

To investigate the correlation between iodine concentration of dual-energy CT (DECT) and histopathology of surgically resected primary lung cancers.

Methods:

We reviewed the medical records, post-operative pathological records and pre-operative DECT images of patients who underwent surgical lung resection for primary lung cancer. After injection of iodinated contrast media, arterial and delayed phases were scanned using 140- and 80-kV tube voltages. Three-dimensional iodine concentration (iodine volume) of primary tumours was calculated using lung nodule application software.

Results:

A total of 60 patients (37 males and 23 females; age range, 39–84 years; mean age, 69 years) with 62 lung cancers were analysed. The resected tumours were histopathologically classified into well-differentiated (G1; n = 20), moderately differentiated (G2; n = 29), poorly differentiated (G3; n = 9) and undifferentiated (G4; n = 4) groups by degree of tumour differentiation (DTD). The mean ± standard deviation of iodine volume at the delayed phase was 59.6 ± 18.6 HU in G1 tumours, 46.5 ± 11.3 HU in G2 tumours, 34.3 ± 15.0 HU in G3 tumours and 28.8 ± 6.4 HU in G4 tumours; significant differences were observed between groups (p < 0.001). Univariate logistic regression analysis showed that iodine volumes both at the early and delayed phases were significantly correlated with DTD (p = 0.006 and p = 0.001, respectively), whereas gender, body weight and tumour size were not (p = 0.084, p = 0.062 and p = 0.391, respectively).

Conclusion:

The iodine volume of lung cancers was significantly associated with their DTD. High-grade tumours tended to have lower iodine volumes than low-grade tumours.

Advances in knowledge:

Iodine volume measured by DECT could be a valuable functional imaging method to estimate differentiation of primary lung cancer.     

Assessment of early therapeutic response to sorafenib in renal cell carcinoma xenografts by dynamic contrast-enhanced and diffusion-weighted MR imaging

Objective:

To investigate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted MRI (DWI) in monitoring early therapeutic response to sorafenib in renal cell carcinoma (RCC) xenograft models.

Methods:

Sorafenib (40 mg kg⁻¹) was administered orally to BALB/c nude mice (n = 9) bearing subcutaneous tumours of human RCC ACHN xenografts. DCE-MRI and DWI were obtained 0, 1, 3 and 7 days after therapy, and DCE-MRI parameters (K^trans and v_e) and apparent diffusion coefficient (ADC) values were calculated. Tumour size and volume changes were correlated with changes in DCE-MRI parameters or ADC values after therapy.

Results:

Following therapy, K^trans showed a significant decrease over time (p = 0.005), whereas v_e did not demonstrate significant changes between time points (p = 0.97). ADC values showed a progressive increase over time (p = 0.004). Compared with pre-therapy, K^trans showed a significant decrease after 3 days of therapy (p = 0.039), and ADC values increased significantly after 7 days (p = 0.039). Tumour size and volume did not show significant changes during 7 days. Tumour size and volume changes were not associated with changes in DCE-MRI parameters or ADC values.

Conclusion:

DCE-MRI and DWI may show early physiological changes within 1 week after initiating sorafenib treatment on human RCC xenografts.

Advances in knowledge:

The quantitative parameters of DCE-MRI and DWI may offer the potential for assessing early therapeutic response to sorafenib in clinical trials.     

Evaluation of Selective Arterial Embolization Effect by Chitosan Micro-Hydrogels in Hindlimb Sarcoma Rodent Models Using Various Imaging Modalities

Purpose

Embolization is mainly used to reduce the size of locally advanced tumors. In this study, selective arterial catheterization with chitosan micro-hydrogels (CMH) into the femoral artery was performed and the therapeutic effect was validated using different imaging methods.

Methods

Male SD rats (n = 18, 6 weeks old) were randomly assigned into three groups: Group 1 as control, Group 2 without any ligation of distal femoral artery, and Group 3 with temporary ligation of the distal femoral artery. RR1022 sarcoma cell lines were inoculated into thigh muscle. After 1 week, CMH was injected into the proximal femoral artery. Different imaging modalities were performed during a 3-week follow-up.

Results

The tumor size was significantly (P < 0.001) decreased in both Group 2 and Group 3 (P < 0.001) after selective arterial embolization therapy. ¹⁸F-FDG-PET/CT revealed decreased intensity of ¹⁸F-FDG uptake in tumors. The accumulation status of ¹²⁵I-CMH near the tumor was verified by gamma camera.

Conclusions

Appropriate selective arterial embolization therapy with CMH was.     

Hepatic radiofrequency ablation: in vivo and ex vivo comparisons of 15-gauge (G) and 17-G internally cooled electrodes

Objective:

To compare the performance of the 15-G internally cooled electrode with that of the conventional 17-G internally cooled electrode.

Methods:

A total of 40 (20 for each electrode) and 20 ablation zones (10 for each electrode) were made in extracted bovine livers and in in vivo porcine livers, respectively. Technical parameters, three dimensions [long-axis diameter (Dl), vertical-axis diameter (Dv) and short-axis diameter (Ds)], volume and the circularity (Ds/Dl) of the ablation zone were compared.

Results:

The total delivered energy was higher in the 15-G group than in the 17-G group in both ex vivo and in vivo studies (8.78 ± 1.06 vs 7.70 ± 0.98 kcal, p = 0.033; 11.20 ± 1.13 vs 8.49 ± 0.35 kcal, p = 0.001, respectively). The three dimensions of the ablation zone had a tendency to be larger in the 15-G group than in the 17-G group in both studies. The ablation volume was larger in the 15-G group than in the 17-G group in both ex vivo and in vivo studies (29.61 ± 7.10 vs 23.86 ± 3.82 cm³, p = 0.015; 10.26 ± 2.28 vs 7.79 ± 1.68 cm³, p = 0.028, respectively). The circularity of ablation zone was not significantly different in both the studies.

Conclusion:

The size of ablation zone was larger in the 15-G internally cooled electrode than in the 17-G electrode in both ex vivo and in vivo studies.

Advances in knowledge:

Radiofrequency ablation of hepatic tumours using 15-G electrode is useful to create larger ablation zones.Radiofrequency ablation (RFA) is the most widely used local ablation technique for the management of primary and metastatic liver tumours. However, previous studies have reported that RFA showed a relatively higher local tumour progression rate than did hepatic resection.^1,2 One of the most important factors affecting local tumour progression was insufficient tumour-free ablation margin of hepatic parenchyma around the tumour margin.^3–6Several strategies have been developed to obtain sufficient ablation margin. In the aspect of RFA techniques, overlapping technique and combined treatment with transcatheter arterial chemoembolization can be used.^7–9 Another strategy is to use switching monopolar, bipolar or multipolar modes to deliver radiofrequency (RF) energy more efficiently.^10,11 Sufficient ablation margin can also be achieved by more efficient electrodes: internally cooled electrode increases the size of ablation zone by preventing charring around the electrode tip.^12,13 Perfusion electrodes can also enlarge the ablation zone by increasing electrical conductance and thermal conductivity.^14–16The diameter of an electrode is also known to be associated with the size of the ablation zone. Theoretically, as the diameter of an electrode becomes larger, the contact surface of the electrode with the surrounding tissue becomes bigger, thereby increasing the active electric field.^17,18 As a result, an electrode with a larger diameter is likely to create a larger ablation zone. In a previous study, Goldberg et al¹⁷ reported that the extent of coagulation necrosis by RFA increases as the diameter of an electrode increases through an in vivo experimental study. However, this study was performed with an electrode without an internal cooling system. Recently, a clinical study comparing therapeutic efficacy and safety between 15-G and 17-G internally cooled electrodes of RFA for hepatocellular carcinoma was published.¹⁹ According to that study, the 15-G internally cooled electrode created a larger ablation volume than did the 17-G electrode. However, the study was limited by selection bias owing to the retrospective study design. In addition, the ablation protocol was not exactly the same between the two groups. Therefore, the issue whether an internally cooled electrode with a larger diameter creates a larger ablation volume should be verified with ex vivo and in vivo experimental studies.The purpose of this experimental study was to compare the performance of the 15-G internally cooled RF electrode with that of the conventional 17-G electrode in both ex vivo and in vivo studies.     

Comparison of therapeutic efficacy and safety of radiofrequency ablation of hepatocellular carcinomas between internally cooled 15-G and 17-G single electrodes

Objective:

To compare the ablation volume, local tumour progression rate and complication rate of radiofrequency ablation (RFA) for small hepatocellular carcinomas (HCCs) using 15-G and 17-G single electrodes.

Methods:

This retrospective study was approved by the institutional review board and informed consent was waived. We reviewed percutaneous RFA cases for HCCs using 15-G or 17-G electrodes without multiple overlapping ablations. A total of 36 pairs of HCCs matched according to tumour size and active tip length were included. We compared ablation volume and complication rate between the two electrode groups. Cumulative local tumour progression rates were estimated using the Kaplan–Meier method and compared using the log-rank test.

Results:

Tumour size and ablation time were not significantly different between the 15-G and 17-G groups (p = 0.661 and p = 0.793, respectively). However, ablation volume in the 15-G electrode group was larger than that in the 17-G group (14.4 ± 5.4 cm³ vs 8.7 ± 2.5 cm³; p < 0.001). No statistical difference in complication rates between the two electrode groups was found. The 10- and 20-month local tumour progression rates were not significantly different between the two groups (2.8% and 5.6% vs 11.1% and 19.3%; p = 0.166).

Conclusion:

Ablation volume by the 15-G electrode was larger than that by the 17-G electrode. However, local tumour progression rate and complication rate were not significantly different between the two electrode groups.

Advances in knowledge:

RFA of HCC using a 15-G electrode is useful to create larger ablation volumes than a 17-G electrode.Radiofrequency ablation (RFA) is now considered to be one of the curative treatment modalities for the management of small hepatocellular carcinomas (HCCs).^1–5 There are various types of electrodes for RFA, including internally cooled electrodes, multi-tined electrodes and perfusion electrodes.^6,7 Among them, an internally cooled electrode is frequently used because it is simple and easy to use. The ablation zone created by an internally cooled electrode is usually cylindrical in shape along the longitudinal axis of the electrode. Hence, the horizontal diameter of the ablation zone is relatively smaller than the longitudinal diameter. Therefore, an internally cooled electrode frequently requires overlapping ablations to achieve a sufficient ablative margin for large tumours (i.e. size >2.5 cm). However, it is sometimes technically difficult to achieve a sufficient ablative margin under ultrasonography guidance since both the boundary of the index tumour and the active tip of the electrode are obscured by the echogenic zone generated by the previous ablation cycle. Therefore, it is ideal to achieve a large ablation zone using a single electrode without multiple overlapping ablations.Electrodes with a larger diameter have a larger contact surface with the surrounding tissue than smaller ones and thereby have a higher active electric field.^8–10 This in turn delivers a larger amount of radiofrequency energy and thus produces a greater amount of heat around the active tip. Consequently, large electrodes create large ablation zones. However, to our knowledge, commercially available internally cooled electrodes are not large and are almost exclusively 17-G.^11,12Recently, larger sized 15-G electrodes have been introduced and used for RFA of liver tumours in our institution. We have found that the 15-G electrode created a larger ablation volume than did the 17-G electrode, while the complication rate differed little. However, to our knowledge, there are no comparative data in the literature regarding the therapeutic efficacy and complication rate after RFA between 15-G and 17-G single electrodes. Hence, the purpose of this study was to evaluate and compare the ablation volume, local tumour progression rate and complication rate after RFA of HCCs using 15-G and 17-G single electrodes.     

Comparison of 18F-fluoride PET/CT, 18F-FDG PET/CT and bone scintigraphy (planar and SPECT) in detection of bone metastases of differentiated thyroid cancer: a pilot study

Objective:

We compared the efficacies of ¹⁸F-fluoride positron emission tomography (¹⁸F-fluoride PET)/CT, ¹⁸F-fludeoxyglucose PET (¹⁸F-FDG PET)/CT, and ^99mTc bone scintigraphy [planar and single photon emission CT (SPECT)] for the detection of bone metastases in patients with differentiated thyroid carcinoma (DTC).

Methods:

We examined 11 patients (8 females and 3 males; mean age ± standard deviation, 61.9 ± 8.7 years) with DTC who had been suspected of having bone metastases after total thyroidectomy and were hospitalized to be given ¹³¹I therapy. Bone metastases were verified either when positive findings were obtained on both ¹³¹I scintigraphy and CT or when MRI findings were positive if MRI was performed.

Results:

Metastases were confirmed in 24 (13.6%) of 176 bone segments in 9 (81.8%) of the 11 patients. The sensitivities of ¹⁸F-fluoride PET/CT and ^99mTc bone scintigraphy (SPECT) were significantly higher than those of ¹⁸F-FDG PET/CT and ^99mTc bone scintigraphy (planar) (p < 0.05). The accuracies of ¹⁸F-fluoride PET/CT and ^99mTc bone scintigraphy (SPECT) were significantly higher than that of ^99mTc bone scintigraphy (planar) (p < 0.05).

Conclusion:

The sensitivity and accuracy of ¹⁸F-fluoride PET/CT for the detection of bone metastases of DTC are significantly higher than those of ^99mTc bone scintigraphy (planar). However, the sensitivity and accuracy of ^99mTc bone scintigraphy (planar) are improved near to those of ¹⁸F-fluoride PET/CT when SPECT is added to a planar scan. The sensitivity of ¹⁸F-FDG PET/CT is significantly lower than that of ¹⁸F-fluoride PET/CT or ^99mTc bone scintigraphy (SPECT).

Advances in knowledge:

This article has demonstrated first the high efficacy of ¹⁸F-fluoride PET/CT for the detection of bone metastases of DTC.Differentiated thyroid carcinoma (DTC) shows a relatively good prognosis compared with carcinomas of other organs, and the 10-year survival rate of DTC is >80% because of treatments such as total thyroidectomy and ablation of remnants with radioiodine.¹ However, metastases of DTC develop in 7–23% of patients; the distant metastases occur commonly in the lungs, bones and brain, and the bones are the second most common site of metastases of DTC.² Bone scintigraphy using ^99mTc-labelled phosphate compounds [^99mTc-methylene diphosphonate (^99mTc-MDP) or ^99mTc-hydroxymethylene diphosphonate (^99mTc-HMDP)] has been widely used for detecting and evaluating bone metastases of various kinds of carcinomas because of its overall high sensitivity and the easy evaluation of the entire skeleton.³ However, there were often false-positive cases in ^99mTc bone scintigraphy, because degenerative or inflammatory foci were often confused with metastatic lesions. The addition of single photon emission CT (SPECT) to planar acquisition of ^99mTc bone scintigraphy has been shown to exhibit a beneficial effect on the detection and evaluation of bone metastases.^4–6 Skeletal imaging by ¹⁸F-fludeoxyglucose positron emission tomography (¹⁸F-FDG PET)/CT has been shown to be useful in the detection of bone metastases of various carcinomas including DTC.⁷Previously, we compared the efficacies of ¹⁸F-FDG PET and planar ^99mTc bone scintigraphy for the detection of bone metastases in patients with DTC.⁸ We found that the specificity and the overall accuracy of ¹⁸F-FDG PET for the detection of bone metastases in patients with DTC were higher than those of planar ^99mTc bone scintigraphy, whereas the difference in the sensitivity of both examinations was not statistically significant, and concluded that ¹⁸F-FDG PET is superior to planar ^99mTc bone scintigraphy because of its lower incidence of false-positive results in the detection of bone metastases of DTC.⁸¹⁸F-fluoride is a positron-emitting bone-seeking radiotracer, which has a similar uptake mechanism to ^99mTc-MDP and ^99mTc-HMDP. As the availability of PET systems was increasing, ¹⁸F-fluoride has been used for skeletal PET imaging since 1990s. PET or PET/CT with ¹⁸F-fluoride have been shown to be more sensitive than planar ^99mTc bone scintigraphy for the detection of bone metastases of lung,⁹ breast,^10,11 hepatocellular,¹² prostate,^11,13,14 colon and bladder¹¹ cancers. However, to the best of our knowledge, there have been no systematic comparative studies on the efficacies of ¹⁸F-fluoride PET/CT, ¹⁸F-FDG PET/CT and ^99mTc bone scintigraphy (planar and SPECT) for the detection of bone metastases of DTC. This study was conducted to compare ¹⁸F-fluoride PET/CT, ¹⁸F-FDG PET/CT and ^99mTc bone scintigraphy (planar and SPECT) in the detection of bone metastases of DTC.     

Triaxial system in bronchial arterial embolization for haemoptysis using N-butyl-2-cyanoacrylate

Objective:

The application of bronchial artery embolization (BAE) using N-butyl-2-cyanoacrylate (NBCA) for haemoptysis was recently reported to be useful. A triple co-axial (triaxial) system consisting of a 4-Fr catheter, 2.7-Fr microcatheter and 1.9-Fr no-taper microcatheter has been developed. The aim of the present study was to evaluate the usefulness of the triaxial system in BAE using NBCA.

Methods:

12 patients with haemoptysis, 8 males and 4 females with a median age of 64 years (range, 49–88 years), underwent BAE between August 2012 and October 2014. Medical records and images were reviewed, and the technical success rate, clinical success rate, haemoptysis-free rate and complications were evaluated. Technical success was defined as the complete cessation of the target artery as confirmed by digital subtraction angiography, whereas clinical success was defined as the cessation of haemoptysis within 24 h of BAE. Recurrent haemoptysis was defined as a total of >30 ml of bleeding per day.

Results:

The target artery was embolized successfully in all patients, and the technical success rate was 100% (12/12). The cessation of haemoptysis was achieved in 11 out of 12 patients within 24 h, and thus, the clinical success rate was 92% (11/12). The 6-, 12- and 24-month haemoptysis-free rates were 89%, 89% and 76%, respectively. No patients exhibited any signs of complications such as spinal ischaemia.

Conclusion:

BAE using the triaxial system and NBCA appears to be a useful and safe procedure for haemoptysis.

Advances in knowledge:

The triaxial system contributes to safe and effective BAE using NBCA.     

Imaging of acute superior mesenteric artery embolus using spectral CT in a canine model

Objective:

To explore the diagnostic value of single-source dual-energy spectral CT (sDECT) imaging in an acute superior mesenteric artery embolus (SMAE) canine model.

Methods:

Pre-contrast and double-phase contrast-enhanced sDECT were performed before and after embolization in eight SMAE dog models. Monochromatic images of embolized intestine with the best contrast-to-noise ratio (CNR) were obtained and compared with the polychromatic images. CT parameters including attenuation value, iodine content, water content and thickness of the embolized intestinal segments were obtained, and normalized difference in iodine concentration (NDIC) was calculated.

Results:

The CNR in pre-contrast, arterial phase and portal venous phase at 4 h after embolization was 1.11 ± 1.23, 13.50 ± 1.54 and 10.63 ± 3.75, respectively, significantly higher than those of the polychromatic images (p < 0.05). The iodine-based images clearly revealed the embolized intestinal segments, which were highly consistent with the gross findings. The difference in attenuation values between the embolization area and non-embolization area in the monochromatic images was 105.06 ± 35.35 HU, higher than that in the polychromatic images (p < 0.001). The attenuation values and NDIC were significantly decreased at 2 h after embolization, relatively increased at 4 h and gradually decreased at 6 and 8 h. The changing pattern of thickness was similar to that of NDIC over time after embolization.

Conclusion:

sDECT can provide the optimal monochromatic images and allow increased detection rates of lesions. sDECT is a very promising tool for quantitative diagnosis of SMAE.

Advances in knowledge:

Our research provides more quantitative parameters for the assessment of SMAE by sDECT.     

Does 131I Radioactivity Interfere with Thyroglobulin Measurement in Patients Undergoing Radioactive Iodine Therapy with Recombinant Human TSH?

Objectives

Recombinant human thyroid-stimulating hormone (rhTSH) is widely used in radioactive iodine therapy (RIT) to avoid side effects caused by hypothyroidism during the therapy. Owing to RIT with rhTSH, serum thyroglobulin (Tg) is measured with high ¹³¹I concentrations. It is of concern that the relatively high energy of ¹³¹I could interfere with Tg measurement using the immunoradiometric assay (IRMA). We investigated the effect of ¹³¹I administration on Tg measurement with IRMA after RIT.

Methods

A total of 67 patients with thyroid cancer were analysed retrospectively. All patients had undergone rhTSH stimulation for RIT. The patients’ sera were sampled 2 days after ¹³¹I administration and divided into two portions: for Tg measurements on days 2 and 32 after ¹³¹I administration. The count per minute (CPM) of whole serum (200 μl) was also measured at each time point. Student’s paired t-test and Pearson’s correlation analyses were performed for statistical analysis.

Results

Serum Tg levels were significantly concordant between days 2 and 32, irrespective of the serum CPM. Subgroup analysis was performed by classification based on the ¹³¹I dose. No difference was noted between the results of the two groups.

Conclusions

IRMA using ¹²⁵I did not show interference from ¹³¹I in the serum of patients stimulated by rhTSH.     

Vaginal displacement during course of adjuvant radiation for cervical cancer: results from a prospective IG-IMRT study

Objective:

To compare internal target volume (ITV) generated using population-based displacements (ITV_study) with empty and full bladder scan fusion (ITV_EBFB) for organ-at-risk (OAR) doses during adjuvant intensity-modulated radiation therapy (IMRT) for cervical cancer.

Methods:

From January 2011 to October 2012, patients undergoing IMRT were included. CT simulation was carried out after inserting vault markers. Planning target volume (PTV)_EBFB received 50 Gy per 25 fractions. Pre-treatment megavoltage CT (MVCT) was performed. MVCTs were registered using bony landmarks with Day 1 MVCT. Displacement of the centre of mass of markers was measured along each axis. Directional ITV was calculated using mean ± 2 standard deviations (SDs) (ITV_study). Replanning was performed using PTV study, and OAR doses were compared with PTV_EBFB using Wilcoxon test.

Results:

A total of 348/386 data sets were evaluable for 16 patients. The median vaginal displacement was 1.2 mm (SD, 1.3 mm), 4.0 mm (SD, 3.5 mm) and 2.8 mm (SD, 3.3 mm) in the mediolateral, superoinferior and anteroposterior directions, respectively. The ITV margins were 4.1, 10.3 and 10.6 mm. ITV_study and ITV_EBFB were 115.2 cm³ (87.7–152.2 cm³) and 151 cm³ (95.7–277.1 cm³) (p < 0.0001), respectively. PTV_study and PTV_EBFB were 814 and 881 cm³ (p < 0.0001), respectively. Median doses to the bladder were lower with the PTV_study (46.2 Gy vs 43.2 Gy; p = 0.0001), and a similar trend was observed in the volume of the small bowel receiving 40 Gy (68.2 vs 60.1 cm³; p = 0.09).

Conclusion:

Population-based PTV margins can lead to reduction in OAR doses.

Advances in knowledge:

Population-based ITV may reduce OAR doses while executing adjuvant IMRT for cervical cancer.Adjuvant pelvic radiation for cervical and endometrial cancers is recommended in patients with adverse histopathological features following surgery.^1,2 Although it improves outcomes, it is associated with increased acute and late bowel morbidity.^1,2 Recently published results of the Radiation Therapy Oncology Group (RTOG) Phase II study demonstrate that the use of pelvic intensity-modulated radiation therapy (IMRT) is associated with reduced treatment-related acute and short-term gastrointestinal (GI) toxicity, and this can be achieved without worsening disease control.³ However, implementing IMRT may be challenging owing to the unpredictable nature of vaginal displacements during the course of external radiation. Therefore, the RTOG recommends that for planning IMRT, both empty and full bladder (EBFB) scans should be obtained for localizing residual vagina and for generating the internal target volume (ITV).⁴ These recommendations are being followed by two ongoing Phase III randomized controlled trials that aim at reducing acute and late bowel toxicity of adjuvant pelvic radiation.^5,6 Although this strategy may ensure that all extreme displacements arising out of variations in bladder filling are accounted for, this may result in increased planning target volume (PTV) and thereby increased dose to adjacent organs at risk (OAR). Strong correlation has been reported between the dose received by the bowel and late bowel morbidity after adjuvant pelvic radiation for cervical cancer.⁷ The present study was initiated with an aim of evaluating vaginal displacement for the post-hysterectomy cohort and to investigate if population-based ITV could reduce dose to OARs.     

Quantitative Measurement of Serum Hepatitis B Surface Antigen Using an Immunoradiometric Assay in Chronic Hepatitis B

Purpose

Measurement of serum hepatitis B virus surface antigen (HBsAg) levels is important for the management of chronic hepatitis B patients in terms of monitoring response to antiviral therapy. This study aimed to evaluate the diagnostic performance of a new diagnostic kit, which quantitatively measures serum HBsAg level using an immunoradiometric assay (IRMA)-based method. Measurements were compared with those obtained using a chemiluminescent microparticle immunoassay (CMIA)-based method.

Methods

The blood samples of 96 patients with chronic hepatitis B were used in this study. Copy numbers of serum hepatitis B virus (HBV) DNA were determined in 23 of these samples. The correlation between and the concordance of IRMA and CMIA results were determined using Pearson’s correlation coefficients. P values of 0.05 were considered to be statistically significant throughout.

Results

Laboratory diagnoses based on IRMA were wholly in agreement with those based on CMIA. Furthermore, serum HBsAg levels by IRMA were found to be highly correlated with those determined by CMIA (correlation coefficient R² = 0.838, p < 0.001). Serum HBsAg level and serum HBV DNA copies were found to be linearly related by both methods (R² = 0.067, p = 0.316 by IRMA, and R² = 0.101, p = 0.215 by CMIA).

Conclusion

The diagnostic performance of the investigated IRMA method of determining HBsAg levels was found to be comparable with that of a CMIA-based method in chronic hepatitis B patients.     

Stereotactic body radiation therapy for a new lung cancer arising after pneumonectomy: dosimetric evaluation and pulmonary toxicity

Objective:

To evaluate the tolerance of stereotactic body radiation therapy (SBRT) for the treatment of secondary lung tumours in patients who underwent previous pneumonectomy.

Methods:

12 patients were retrospectively analysed. The median maximum tumour diameter was 2.1 cm (1–4.5 cm). The median planning target volume was 20.7 cm³ (2.4–101.2 cm³). Five patients were treated with a single fraction of 26 Gy and seven patients with fractionated schemes (3 × 10 Gy, 4 × 10 Gy, 4 × 12 Gy). Lung toxicity, correlated with volume (V) of lung receiving >5, >10 and >20 Gy, local control and survival rate were assessed. Median follow-up was 28 months.

Results:

None of the patients experienced pulmonary toxicity > grade 2 at the median dosimetric lung parameters of V₅, V₁₀ and V₂₀ of 23.1% (range 10.7–56.7%), 7.3% (2.2–27.2%) and 2.7% (0.7–10.9%), respectively. No patients required oxygen or had deterioration of the performance status during follow-up if not as a result of clinical progression of disease. The local control probability at 2 years was 64.5%, and the overall survival at 2 years was 80%.

Conclusion:

SBRT appears to be a safe and effective modality for treating patients with a second lung tumour after pneumonectomy.

Advances in knowledge:

Our results and similar literature results show that when keeping V₅, V₁₀ V₂₀ <50%, <20% and <7%, respectively, the risk of significant lung toxicity is acceptable. Our experience also shows that biologically effective dose 10 >100 Gy, necessary for high local control rate, can be reached while complying with the dose constraints for most patients.     

Acceptance,commissioning and clinical use of the WOmed T-200 kilovoltage X-ray therapy unit

Objective:

The objective of this work was to characterize the performance of the WOmed T-200-kilovoltage (kV) therapy machine.

Methods:

Mechanical functionality, radiation leakage, alignment and interlocks were investigated. Half-value layers (HVLs) (first and second HVLs) from X-ray beams generated from tube potentials between 30 and 200 kV were measured. Reference dose was determined in water. Beam start-up characteristics, dose linearity and reproducibility, beam flatness, and uniformity as well as deviations from inverse square law were assessed. Relative depth doses (RDDs) were determined in water and water-equivalent plastic. The quality assurance program included a dosimetry audit with thermoluminescent dosemeters.

Results:

All checks on machine performance were satisfactory. HVLs ranged between 0.45–4.52 mmAl and 0.69–1.78 mmCu. Dose rates varied between 0.2 and 3 Gy min⁻¹ with negligible time-end errors. There were differences in measured RDDs from published data. Beam outputs were confirmed with the dosimetry audit. The use of published backscatter factors was implemented to account for changes in phantom scatter for treatments with irregularly shaped fields.

Conclusion:

Guidance on the determination of HVL and RDD in kV beams can be contradictory. RDDs were determined through measurement and curve fitting. These differed from published RDD data, and the differences observed were larger in the low-kV energy range.

Advances in knowledge:

This article reports on the comprehensive and novel approach to the acceptance, commissioning and clinical use of a modern kV therapy machine. The challenges in the dosimetry of kV beams faced by the medical physicist in the clinic are highlighted.     

Transcutaneous oxygen tension measurements following peripheral transluminal angioplasty procedure has more specificity and sensitivity than ankle brachial index

Objective:

To evaluate the superiority of transcutaneous oxygen pressure (TcPO₂) before, during and after peripheral transluminal angioplasty (PTA) in comparison with ankle brachial index (ABI) in patients with diabetes.

Methods:

40 consecutive patients with diabetes treated by PTA where included. This study shows results before, during and after PTA and their progression for 8 weeks.

Results:

The TcPO₂ increased from 28.11 ± 8.1 to 48.03 ± 8.4 mmHg, 8 weeks after PTA (p < 0.001). The ABI increased from 0.48 ± 0.38 to 0.77 ± 0.39 after PTA (p < 0.001). After PTA, the stenosis of the vessel decreased from 58.33 ± 20.07% to 21.87 ± 13.57% (p < 0.001). TcPO₂ was determined in all the patients, but ABI could not be determined in all patients. Furthermore, we determined patients with “false negatives” with an improvement in ABI and “false positives” in 12.5% of patients. Additionally, in this study, we monitored TcPO₂ while performing PTA, revealing variations in each phase of the radiological procedure.

Conclusion:

The increase in TcPO₂ measurements following PTA procedure has more specificity and sensitivity than does ABI. The use of TcPO₂ may represent a more accurate alternative than traditional methods (ABI) used in assessing PTA results. The TcPO₂ also allows the radiologist to assess changes in tissue oxygenation during PTA, allowing changes to the procedure and subsequent treatment.

Advances in knowledge:

This is the first time that a graph is shown with TcPO₂ results during PTA performance in many patients.Critical limb ischaemia (CLI) is defined as a state of arterial insufficiency that reduces distal perfusion pressure to such an extent that microcirculation and nutrient blood flow to tissues are severely disturbed.¹ Peripheral transluminal angioplasty (PTA) has become an accepted endovascular treatment modality for patients with CLI. The effectiveness of PTA is assessed by determining peripheral pulses, the calculation of ankle brachial index (ABI) or the calculation of the toe brachial index.²However, patients with diabetes with CLI have features that hinder the use of these parameters in assessing the success of PTA.³ Calcification of the arterial wall, complete obstruction of the artery and the presence of collateral circulation cause problems in ABI determinations that exclude up to 30% of patients treated with PTA^4,5 from evaluation. It has even been found that 27% of patients with diabetes successfully treated by PTA, finally had to undergo amputation owing to vascular complications.⁶Currently, the increasing prevalence of diabetic vascular disease induces a bigger number of PTA in patients with diabetes with CLI. Radiologists perform successful PTA that significantly reduces arterial stenosis but does not always lead to an improvement in distal reperfusion. Microcirculation is the most relevant indicator of skin health and therefore wound healing and an improvement of the oxygen pressure. The transcutaneous oxygen pressure (TcPO₂) is an indicator of oxygen and nutrients reaching the tissues through microcirculation.^2,4 The aim of this study was to evaluate TcPO₂ before, during and after PTA in comparison with ABI in patients with diabetes.     

Long-term results of microcoil embolization for colonic haemorrhage: how common is rebleeding?

Objective:

To determine the long-term results of patients undergoing transcatheter coil embolization for the treatment of acute colonic haemorrhage.

Methods:

Patients undergoing angiography for suspected colonic bleeding between January 2002 and December 2012 were reviewed (average age, 60 years; 38.4% male). Baseline, procedural and outcome parameters were recorded following the Society of Interventional Radiology guidelines. Primary outcome measures included early (<30 days) and delayed (>30 days) rebleeding events and adverse procedure-related complication. Average follow-up time was 996 days (median, 232 days; range, 30–3663 days).

Results:

One or multiple sites of bleeding were identified in 40 cases. Coil embolization was performed in 39 patients, 26 (66.7%, 26/39) of whom were treated successfully without technical/clinical failure (n = 12) or loss to follow-up (n = 1). Three patients (11.5%, 3/26) rebled in the early period within 30 days; one patient went on to hemicolectomy. Four patients (15.3%, 4/26) experienced delayed rebleeding after 30 days; two of whom also underwent hemicolectomy. No major complication occurred. One minor complication of short segment arterial dissection was seen in the clinical failure group. One case of asymptomatic ischaemia was identified on a patient undergoing pre-operative colonoscopy for elective bowel resection. No instances of ischaemic stricture were seen. All-cause mortality of successfully treated and all patients at 1 year was 31% (8/26) and 30% (12/40), respectively.

Conclusion:

Transcatheter coil embolization is a durable treatment option with a technical and clinical success rate of 67% in the setting of acute colonic haemorrhage. A modest level of rebleeding was seen among successfully treated patients in both the early and delayed periods; in the majority of patients, embolization proved to be definitive therapy.

Advances in knowledge:

Transcatheter coil embolization is a durable and potentially definitive therapy in the management of acute colonic haemorrhage.Acute lower gastrointestinal (GI) bleeding, defined by bleeding distal to the ligament of Treitz, is a potentially life-threatening condition that is often treated conservatively by medical management alone. Colonic haemorrhage constitutes the predominant subset of lower GI bleeding cases, occurring in up to 75–90% of patients and is commonly owing to bleeding diverticula, angiodysplasia, inflammatory bowel disease or neoplasm.¹ In up to 20% of these patients, haemorrhage is classified as massive, requiring blood transfusions greater than 3–5 units of packed red blood cells (RBCs) to maintain haemodynamic stability.² In these instances, more invasive management for haemostasis is necessary, with treatment options including endoscopic therapy (i.e. colonoscopy), transcatheter embolization and/or surgery.In the past two decades, suboptimal performance of alternative endovascular techniques such as vasopressin infusion and continued developments in coaxial catheter technique for transcatheter coil embolization have resulted in its increased usage by demonstrating an increased effectiveness at controlling life-threatening bleeding from a minimally invasive approach.^3,4 Despite these advances, few studies to date have evaluated the long-term efficacy of superselective transcatheter microcoil embolization in the treatment of colonic haemorrhage. Given that embolization treats a symptom (i.e. bleeding in a patient with diverticulosis) of an underlying problem rather than the problem itself, recurrence is a concern. The purpose of this study is to retrospectively review all transcatheter microcoil embolizations undertaken at our institution for acute colonic bleeding to determine the short-term clinical outcome and long-term durability of this treatment.