Efficacy of Bortezomib for Treating Anti-Interferon-Gamma Autoantibody-Associated Adult-Onset Immunodeficiency Syndrome.

BACKGROUND: Currently, there is no effective treatment for adult-onset immunodeficiency (AOID) syndrome with anti-interferon-gamma autoantibodies (anti-IFN-γ-auto-Abs). This study aimed to investigate the effectiveness of bortezomib (BTZ) for decreasing anti-IFN-γ-auto-Abs. METHODS: A pre- and post-intervention study was conducted from February 2017 through June 2019 at Siriraj Hospital (Bangkok, Thailand). Five patients were invited to receive once-weekly BTZ (1.3 mg/m2 body surface area) subcutaneously for 8 weeks followed by oral cyclophosphamide (1 mg/kg/d) for 4 months. The primary outcomes were the difference in antibody level at 8 and 48 weeks compared with baseline and the incidence of serious adverse events (AEs). The secondary outcome was the occurrence of opportunistic infections (OIs) during the 72 weeks after starting BTZ. RESULTS: The median patient age was 46 years (range, 34-53). All patients had 3-5 OIs prior to enrollment. All patients were receiving antimycobacterial agents for treatment of nontuberculous mycobacterial infection at enrollment. There was no significant difference in the mean optical density of auto-Abs at 8 weeks (3.73 ± 0.72) or 48 weeks (3.74 ± 0.53) compared with baseline (3.84 ± 0.49; P = .336 and P = .555, respectively). However, after serum dilution, the antibody titer nonsignificantly decreased 8-16 weeks after BTZ initiation (P = .345). Ten OIs were observed 24-72 weeks after BTZ initiation. CONCLUSIONS: Treatment with BTZ followed by cyclophosphamide yielded no significant decrease in antibody titer levels, and 10 OIs were observed during 24-72 weeks of BTZ treatment. No serious AEs were observed. Combining rituximab with BTZ is likely necessary to prevent generation of new autoantibody-producing plasma cells. Clinical Trials Registration. NCT03103555.

Automated segmentation of lung, liver, and liver tumors from Tc-99m MAA SPECT/CT images for Y-90 radioembolization using convolutional neural networks.

PURPOSE: 90 Y selective internal radiation therapy (SIRT) has become a safe and effective treatment option for liver cancer. However, segmentation of target and organ-at-risks is labor-intensive and time-consuming in 90 Y SIRT planning. In this study, we developed a convolutional neural network (CNN)-based method for automated lungs, liver, and tumor segmentation on 99m Tc-MAA SPECT/CT images for 90 Y SIRT planning. METHODS: 99m Tc-MAA SPECT/CT images and corresponding clinical segmentations were retrospectively collected from 56 patients who underwent 90 Y SIRT. The collected data were used to train three CNN-based segmentation algorithms for lungs, liver, and tumor segmentation. Segmentation performance was evaluated using the Dice similarity coefficient (DSC), surface DSC, and average symmetric surface distance (ASSD). Dosimetric parameters (volume, counts, and lung shunt fraction) were measured from the segmentation results and were compared with clinical reference segmentations. RESULTS: The evaluation results show that the method can accurately segment lungs, liver, and tumor with median [interquartile range] DSCs of 0.98 [0.97-0.98], 0.91 [0.83-0.93], and 0.85 [0.71-0.88]; surface DSCs of 0.99 [0.97-0.99], 0.86 [0.77-0.93], and 0.85 [0.62-0.93], and ASSDs of 0.91 [0.69-1.5], 4.8 [2.6-8.4], and 4.7 [3.5-9.2] mm, respectively. Dosimetric parameters from the three segmentation networks show relationship with those from the reference segmentations. The overall segmentation took about 1 min per patient on an NVIDIA RTX-2080Ti GPU. CONCLUSION: This work presents CNN-based algorithms to segment lungs, liver, and tumor from 99m Tc-MAA SPECT/CT images. The results demonstrated the potential of the proposed CNN-based segmentation method for assisting 90 Y SIRT planning while drastically reducing operator time.

Outcomes following I-131 treatment with cumulative dose exceeding or equal to 600 mCi in differentiated thyroid carcinoma patients.

To evaluate treatment outcomes following radioactive iodine (RAI) treatment with a cumulative dose of ≥≥600 mCi in differentiated thyroid carcinoma (DTC) patients, a retrospective review of medical records was done in 176 DTC patients with a cumulative dose of ≥600 mCi from January 1993 to December 2013. All patients were followed up for at least 2 years after receiving 600 mCi of I-131 treatment. Remission criteria were no clinical and imaging evidence of disease and low serum thyroglobulin levels during thyroid-stimulating hormone suppression of <0.2 ng/ml or of <1 ng/ml after stimulation in the absence of interfering antibodies. A total of 176 patients were included in the study: 137 - papillary thyroid cancer, 29 - follicular thyroid cancer, 9 - mixed papillary and follicular thyroid cancer, and 1 - Hurthle cell carcinoma. Most of the patients (118, 67%) had locoregional metastasis, whereas 48 patients (27%) had distant metastases at presentation. The median cumulative dose was 900 mCi (range: 600-2200 mCi). The mean follow-up period was 82.84 ± 42.41 months. Only 16 patients (9.1%) met remission criteria at the end of treatment. The rest of patients (160, 90.9%) were not remitted: stable disease in 94 (53.4%), at least 1 metastasis without I-131 uptake in 34 (19.3%), progressive disease in 21 (11.9%), and death during the whole follow-up period in 11 (6.3%). Two patients (1.1%) developed second primary malignancy. Eighteen cases were suspected of bone marrow suppression (14 cases [7.9%] had anemia and 5 cases [2.8%] had neutropenia). Seven patients (3.9%) developed permanent salivary gland dysfunction. Although the complications after receiving RAI treatment with a cumulative dose of ≥≥600 mCi were low and not severe, the patients with remission were in <10%. Our study suggests that the decision to administer further treatments should be made on an individual basis because beneficial effects may be controversial.

Sequential 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) scan findings in patients with extrapulmonary tuberculosis during the course of treatment-a prospective observational study.

BACKGROUND: Initial studies of tuberculosis (TB) in macaques and humans using 18F-FDG positron emission tomography (PET) imaging as a research tool suggest its usefulness in localising disease sites and as a clinical biomarker. Sequential serial scans in patients with extrapulmonary TB (EPTB) could inform on the value of PET-CT for monitoring response to treatment and defining cure. PATIENTS AND METHODS: HIV-negative adults with EPTB from eight sites across six countries had three 18F-FDG PET/CT scans: (i) within 2 weeks of enrolment, (ii) at 2 months into TB treatment and (iii) at end of ATT treatment. Scanning was performed according to the EANM guidelines. 18F-FDG PET/CT scans were performed 60 ± 10 min after intravenous injection of 2.5-5.0 MBq/kg of 18F-FDG. FINDINGS: One hundred and forty-seven patients with EPTB underwent 3 sequential scans. A progressive reduction over time of both the number of active sites and the uptake level (SUVmax) at these sites was seen. At the end of WHO recommended treatment, 53/147 (36.0%) patients had negative PET/CT scans, and 94/147 (63.9%) patients remained PET/CT positive, of which 12 patients had developed MDR TB. One died of brain tuberculoma. INTERPRETATION: Current 18F-FDG PET/CT imaging technology cannot be used clinically as a biomarker of treatment response, cure or for decision-making on when to stop EPTB treatment. PET/CT remains a research tool for TB and further development of PET/CT is required using new Mycobacterium tuberculosis-specific radiopharmaceuticals targeting high-density surface epitopes, gene targets or metabolic pathways.

PET/CT features of extrapulmonary tuberculosis at first clinical presentation: a cross-sectional observational 18F-FDG imaging study across six countries.

BACKGROUND: A large proportion of the huge global burden of extrapulmonary tuberculosis (EPTB) cases are treated empirically without accurate definition of disease sites and extent of multi-organ disease involvement. Positron emission tomography (PET) imaging using 2-deoxy-2-(fluorine-18) fluoro-d-glucose (18F-FDG) in tuberculosis could be a useful imaging technique for localising disease sites and extent of disease. METHODS: We conducted a study of HIV-negative adult patients with a new clinical diagnosis of EPTB across eight centres located in six countries: India, Pakistan, Thailand, South Africa, Serbia and Bangladesh, to assess the extent of disease and common sites involved at first presentation. 18F-FDG PET/computed tomography (CT) scans were performed within 2 weeks of presentation. FINDINGS: 358 patients with EPTB (189 females; 169 males) were recruited over 45 months, with an age range of 18-83 years (females median 30 years; males median 38 years). 350 (98%) out of 358 patients (183 female, 167 male) had positive scans. 118 (33.7%) out of 350 had a single extrapulmonary site and 232 (66.3%) out of 350 had more than one site (organ) affected. Lymph nodes, skeleton, pleura and brain were common sites. 100 (28%) out of 358 EPTB patients had 18F-FDG PET/CT-positive sites in the lung. 110 patients were 18F-FDG PET/CT-positive in more body sites than were noted clinically at first presentation and 160 patients had the same number of positive body sites. INTERPRETATION: 18F-FDG PET/CT scan has potential for further elucidating the spectrum of disease, pathogenesis of EPTB and monitoring the effects of treatment on active lesions over time, and requires longitudinal cohort studies, twinned with biopsy and molecular studies.

Optimization of imaging protocols for myocardial blood flow (MBF) quantification with 18F-flurpiridaz PET.

The new PET tracer, 18F-flurpiridaz, with high myocardial extraction allows quantitative myocardial blood flow (MBF) estimation from dynamic PET data and tracer kinetic modeling. The goal of this study is to determine the optimal imaging protocols and parameters using a realistic simulation study. The time activity curves (TACs) of different tissue organs from a 30-s infusion time (IT) of 18F-flurpiridaz in a dynamic PET study were extracted from a previous study. The TACs at different time points were incorporated in a series of realistic 3D XCAT phantoms from which the parameters of a 2-compartment model and the 'true' MBF of 18F-flurpiridaz were determined. The compartmental model was used to generate TACs from 7 additional ITs. PET projection data from the XCAT phantoms were generated using Monte Carlo simulation. They were reconstructed using an OS-EM reconstruction algorithm with different update number (N) to obtain dynamic PET images. The blood and myocardial TACs were derived from the dynamic images from which the MBF and %MBF error was estimated. The %MBF error decreases with increasing N of the OS-EM and levels off after ∼42. The 30-s IT gave the smallest %MBF error that decreases from ∼0.57% to ∼19.40%. The MBF for 2-min, 4-min, 8-min and 16-min IT were statistically significant different from the MBF for 30-s IT (P<0.05). Too fast or too slow infusion time gave higher %MBF error. The optimal imaging protocol in dynamic 18F-flurpiridaz PET for accurate quantitative MBF estimation was 30-s IT and N of ∼42 for the OS-EM.

A Comparison of Accuracy of Planar and Evolution SPECT/CT Bone Imaging in Differentiating Benign from Metastatic Bone Lesions.

Objective: To compare sensitivity, specificity, accuracy and diagnostic confidence in the differentiation between benign and metastatic bone lesions on whole body planar bone scintigraphy and Evolution SPECT/CT. Material and Method: Eighty diagnosed or suspected cancer patients with indeterminate lesions on planar scintigraphy were recruited in the present prospective study. Additional whole body Evolution SPECT/CT was performed after whole body planar scintigraphy. All lesions on both imagings were categorized into 5 categories; definitely metastasis, probably metastasis, indeterminate, probably benign and definitely benign. The diagnosis of each lesion was confirmed by follow-up imaging, pathological findings or clinical follow-up for at least 6 months. Results: Detected lesions on planar scintigraphy and Evolution SPECT/CT imaging were 442 and 477 lesions, respectively.The sensitivity, specificity and accuracy of planar scintigraphy and Evolution SPECT/CT imaging in the diagnosis of metastatic lesions were 27% (95% CI: 13.8, 44.1), 63.2% (95% CI: 58.5, 67.7), 60%, and 97.3% (95% CI: 85.8, 99.9), 100% (95% CI: 96.4, 100) and 99.8%, respectively. Indeterminate lesions on planar scintigraphy were 34.2% (151 lesions from total 442 lesions, which 135 of these 151 indeterminate lesions or 89.4% were located in axial skeleton). Evolution SPECT/CT images were able to characterize all indeterminate lesions. Conclusion: Differentiation of benign and metastatic lesions by Evolution SPECT/CT images has superior diagnostic performance and diagnostic confidence over the planar scintigraphy. Thus, Evolution SPECT/CT images should be considered in characterization of indeterminate lesions on planar scintigraphy, especially in the axial skeleton.

Factors Influencing the Success of the First Radioiodine Therapy for Differentiated Thyroid Carcinoma.

Objective: Differentiated thyroid cancer (DTC) has a favorable prognosis following treatment by thyroidectomy and subsequent post-operative radioactive iodine therapy (RAIT). However, prognostic factors for the success of the first RAIT remain inconclusive. The aim of the present study was to evaluate prognostic factors for the success of the first RAIT in DTC patients. Material and Method: We retrospectively studied 401 DTC patients who underwent total, near-total and subtotal thyroidectomy followed by high dose RAIT from 1994 to 2004. Successful RAIT was assessed using the following criteria: (a) stimulated serum thyroglobulin (sTg) < 10 ng/ml; (b) negative diagnostic 131I total body scan (DxTBS); and (c) no serial increase in thyroglobulin antibody (TgAb) levels. Factors influencing successful first RAIT were evaluated. Results: In total, 401 patients were enrolled into the present study. Most patients were female (81.5%) and had papillary cell type cancer (74.3%). Median tumor size was 2.55 cm. (range, 0­11 cm). Metastases at cervical node and distant sites were found prior to RAIT in 167 and 26 patients, respectively. The first RAIT doses of 2.96­3.7, 5.5 and 7.4 GBq were administered to 133, 262 and 6 patients, respectively. Overall success rate of the first RAIT was 32.9%. From univariate analysis, female sex, age of <45 years, underwent thyroidectomy without cervical lymph node dissection, no multifocality, free surgical margin, no metastasis and sTg of <20 ng/dl at ablation were prognostic factors. Age of <45 years and sTg of <20 ng/dl at ablation were independent significant prognostic factors (both p<0.001) from multivariate analysis. Conclusion: Age below 45 years and sTg below 20 ng/dl at ablation are independent prognostic factors for the success of the first RAIT.

Metastatic Neuroendocrine Carcinoma of the Breast Identified by Tc-99m-HYNIC-TOC SPECT/CT: A Rare Case Report.

The authors reported an uncommon presentation of metastatic neuroendocrine carcinoma to the breast detected by Tc-99m-HYNIC-TOC SPECT/CT in a 49 years old woman who, previously, had carcinoid tumor of left main bronchus and invasive ductal carcinoma of the right breast. Later, the patient developed left breast mass. Core needle biopsy of the mass revealed poorly differentiated invasive ductal carcinoma. The disease remained stable for 12 years without any treatment on that left breast (due to patient's rejection). On the later investigation using Tc-99m-HYNIC-TOC scintigraphy examination, rather than invasive ductal carcinoma, metastatic neuroendocrine cancer was suggested. The final diagnosis was confirmed by pathological examination after surgical excision. Multiple metastatic lesions of neuroendocrine carcinoma at lung, liver, ovaries, and bones were also depicted. Due to the good behavior of the disease, patient had been doing well for eight months, without specific treatment. This report confirmed the advantage and the accuracy of Tc-99m-HYNIC-TOC scintigraphy in detection of neuroendocrine carcinoma. Furthermore, metastatic neuroendocrine tumor should be in differential diagnosis for patient with breast mass together with history of neuroendocrine tumor

Optimization and evaluation of reconstruction-based compensation methods and reconstruction parameters for Tc-99m MIBI parathyroid SPECT.

The value of Tc-99m MIBI parathyroid SPECT for localizing parathyroid hyperplasia in chronic renal failure patients remains inconclusive due to limited image quality. Advanced reconstruction methods to improve image quality have been developed but require optimization and evaluation. The goal of this study was to optimize and evaluate compensation methods and reconstruction parameters for Tc-99m MIBI parathyroid SPECT. A phantom population and projection data that modelled clinically realistic variations found in patients were simulated. The 3D OS-EM reconstruction with compensation for attenuation, detector response and scatter in various combinations were studied. For each compensation, the number of updates for OS-EM and the cutoff frequency of a 3D Butterworth filter were optimized and evaluated using anthropomorphic model observer. With optimal parameters, the method with compensation for attenuation and detector response, with or without the addition of scatter compensation, provided the highest lesion detectability for Tc-99m MIBI parathyroid SPECT.

Severe hyponatremia: a comorbidity with I131 therapy in a patient with papillary thyroid cancer.

Hyponatremia is the most common electrolyte disorder in hospitalized patients, especially in elderly patients, in which morbidity varies widely in severity. A 64-year-old Thai woman with papillary thyroid cancer who developed hypothyroid state after thyroid hormone withdrawal for preparation of 1-131 treatment, had severe hyponatremia within the day of 1-131 administration. It is possible that the combination of old age, hypothyroidism, severe nausea and vomiting, and inappropriate secretion of antidiuretic hormone (SIADH) may all have precipitated the severe hyponatremia in the presented case.

Normal Solid Gastric Emptying Values Measured by Scintigraphy Using Asian-style Meal:A Multicenter Study in Healthy Volunteers.

BACKGROUND/AIMS: To report gastric emptying scintigraphy, normal values should be established for a specific protocol. The aim of this study was to provide normal gastric emptying values and determine factors affecting gastric emptying using Asian rice-based meal in healthy volunteers. METHODS: One hundred and ninety-two healthy volunteers were included at 7 tertiary care centers across Thailand. Gastric emptying scintigraphy was acquired in 45 degree left anterior oblique view immediately after ingestion of a 267 kcal steamed-rice with technetium-99m labeled-microwaved egg meal with 100 mL water for up to 4 hours. RESULTS: One hundred and eighty-nine volunteers (99 females, age 43 ± 14 years) completed the study. The medians (5-95th percentiles) of lag time, gastric emptying half time (GE T1/2) and percent gastric retentions at 2 and 4 hours for all volunteers were 18.6 (0.5-39.1) minutes, 68.7 (45.1-107.8) minutes, 16.3% (2.7-49.8%) and 1.1% (0.2-8.8%), respectively. Female volunteers had significantly slower gastric emptying compared to male (GE T1/2, 74 [48-115] minutes vs. 63 (41-96) minutes; P < 0.05). Female volunteers who were in luteal phase of menstrual cycle had significantly slower gastric emptying compared to those in follicular phase or menopausal status (GE T1/2, 85 [66-102] mintes vs. 69 [50-120] minutes or 72 [47-109] minutes, P < 0.05). All of smoking volunteers were male. Smoker male volunteers had significantly faster gastric emptying compared to non-smoker males (GE T1/2, 56 [44-80] minutes vs. 67 [44-100] minutes, P < 0.05). Age, body mass index and alcohol consumption habits did not affect gastric emptying values. CONCLUSIONS: A steamed-rice with microwaved egg meal was well tolerated by healthy volunteers. Gender, menstrual status and smoking status were found to affect solid gastric emptying.

Cost-effectiveness analysis of 18F-FDG PET/CT in detecting suspected recurrence or metastasis in well-differentiated thyroid carcinoma patients with negative diagnostic total body scan in Thailand: a decision analysis.

OBJECTIVE: To evaluate cost-effectiveness analysis of 18F-FDG PET/CT to detect tumor recurrence or metastasis in well-differentiated thyroid cancer patients with high Tg but negative TBS in Thailand. MATERIAL AND METHOD: A retrospective literature review of 55 studies published between 1978 and 2010 was done. Decision analysis by TreeAge program showed an evaluation of the most cost-effective treatment and 18F-FDG PET/CT scan in thyroid cancer patients with high Tg but negative TBS. The incremental cost and life years gained associated with seven strategies approached were analyzed by the decision tree model. The first strategy was treatment with empirical high dose 131I therapy. The second to the seventh strategies were using imaging investigations by CT scan of neck and chest, 99mTc MIBI scan, and 18F-FDG PET/CT scan to identify recurrent, persistent, and metastatic lesions before the specific treatment via curative surgery, external radiotherapy, and high dose 131I therapy. All strategies were adopted using hospital perspective and direct medical cost was estimated based on the reference price of Siriraj Hospital. Deterministic sensitivity analysis was conducted to investigate the effect of the cost of PET/CT scan. RESULTS: The strategy using 18F-FDG PET/CT scan to detect recurrence or metastasis and possible curative surgery in operable cases and high dose 131I therapy in inoperable cases gave the highest life years gained of 27.08 with cost of 90,227.61 Baht (2,926.24 US dollars) and acceptable incremental cost effectiveness ratio (ICER) of 6,936.88 Baht (224.98 US dollars) per life year gained when compared to the least costly strategy using 99mTc MIBI scan and additional 18F-FDG PET/CT scan in negative MIBI result. Other strategies were dominated by this PET/CT strategy. Deterministic sensitivity analysis (based on the willingness to pay (WTP) 360,000 Baht (11,675.42 US dollars) showed that the cost of PET/CT scan has no impact on the net health benefit. CONCLUSION: Based on the hospital perspective, the cost-effectiveness of 18F-FDG PET/CT scan in detecting suspected recurrence or metastasis in thyroid carcinoma patients with negative diagnostic TBS but high Tg was first done using 18F-FDG PET/CT scan to identify disease, followed by curative surgery or high dose 131I therapy. Moreover cost of PET/CT scan did not influence the net health benefit. This PET/CT benefit is helpfulfor considering the proper PET/CT use for thyroid cancer in Thailand.

The correlation of post-operative radioiodine uptake and Tc-99m pertechnetate thyroid scintigraphy and the result of thyroid remnant ablation.

OBJECTIVE: Determine the relationship between postoperative thyroid remnant using 24 h radioiodine uptake and Tc-99m pertechnetate scintigraphy, and the success of high dose radioiodine ablation. MATERIAL AND METHOD: Retrospectively enrolled 250 patients with DTC who underwent thyroidectomy and radioiodine ablation. Postoperative Tc-99m pertechnetate and 24 h 1-131 uptake were reviewed to evaluate thyroid remnant and the directly compared with ablation outcome. The successful ablation was defined using negative WBS and stimulated Tg < 10 ng/ml in the absence of TgAb at six to 12 months after treatment. The relationship between success of ablation and other variables were evaluated RESULTS: One hundred twenty four patients (49.6%) were successfully ablated after single high dose radioiodine ablation. The authors found no association with age, sex, extent of surgery, tumor histology, tumor size, mutifocal, extrathyroidal invasion, 1-131 administered dose, interval from surgery to radioiodine ablation, Tc-99m pertechnetate scan, or 24 h 1-131 uptake, and successful ablation. The initial Tg level was the only variable found to be associated with success (p < 0.001). CONCLUSION: Neither Tc-99m pertechnetate thyroid scintigraphy nor 24 h 1-131 uptake percentage in the evaluation of postsurgical thyroid remnant can predict radioiodine ablation outcome in patients with DTC. Serum Tg level at the time of ablation could be a reasonable predictor of the success of ablation.

Prevalence of dry eye syndrome and Sjogren's syndrome in patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis has manifestations in various organs including ophthalmic involvement. The present study evaluates prevalence of dry eye and secondary Sjogren's syndrome using salivary scintigraphy which has not been used in previous reports. OBJECTIVE: To evaluate the prevalence of secondary Sjogren's syndrome in patients with rheumatoid arthritis, including clinical characteristics and dry eye, compared with non-Sjogren's syndrome. DESIGN: Descriptive cross sectional study MATERIAL AND METHOD: Sixty-one patients with rheumatoid arthritis were recruited at Siriraj Hospital during March 2009-September 2010 and filled in the questionnaires about dry eye for Ocular Surface Disease Index (OSDI) with a history taking of associated diseases, medications, duration of symptoms of dry eyes and dry mouth. The Schirmer I test without anesthesia, tear break-up time, rose bengal staining score, severity of keratitis and salivary scintigraphy were measured and analyzed. RESULTS: Prevalence of secondary Sjogren's syndrome and dry eye were 22.2% (95% CI 15.4 to 30.9) and 46.7% (95% CI 38.0 to 55.6), respectively. Dry eye interpreted from OSDI, Schirmer 1 test, tear break-up time and rose bengal staining was 16.4%, 46.7%, 82% and 3.3% respectively. Fifty-two percent of patients had a history of dry eye and dry mouth with mean duration 27.4 and 29.8 months, respectively. Superficial punctate keratitis and abnormal salivary scintigraphy were found in 58.2% and 77.8%. Duration of rheumatoid arthritis, erythrocyte sedimentation rate were not correlated with secondary Sjogren's syndrome. Dry eye from OSDI with secondary Sjogren's syndrome (33.3%) compared with non-Sjogren's syndrome (9.5%) was significant difference (p = 0.008). Adjusted odds ratio for secondary Sjogren's syndrome in OSDIL score > 25 was 13.8 (95% CI 2.6 to 73.8, p = 0.002) compared to OSDI score < 25. CONCLUSION: Awareness and detection of dry eye syndrome and secondary Sjogren's syndrome in rheumatoid arthritis was crucial for evaluation of their severity and proper management.

A prospective randomized study of the efficacy and cost-effectiveness of high and low dose regimens of I-131 treatment in hyperthyroidism.

OBJECTIVE: To compare the efficacy and cost-effectiveness of high and low dose regimens of I-131 treatment in patients with hyperthyroidism. MATERIAL AND METHOD: One hundred fifty patients with proven hyperthyroidism were randomly allocated into the high (74 patients) and low (76 patients) dose regimen of I-131 treatment. Four patients of the high dose group and one patient of the low dose group were excluded because of lost follow-up. A gland-specific dosage was calculated on the estimated weight of thyroid gland and 24-hour I-131 uptake. The high and low I-131 dose regimens were 150 microCi/gm and 100 microCi/gm, respectively. The first mean radioiodine activity administered to the high and low dose group was 10.2 and 8 mCi, respectively. Repeated treatment was given to 25 patients of the high dose group and 40 patients of the low dose group. Clinical outcome and calculated costs for outpatient attendances, and laboratory tests together with initial and subsequent treatments were evaluated for one year after I-131 treatment. Elimination of hyperthyroidism that resulted in either euthyroidism or hypothyroidism was classified as therapeutic success. The cost effectiveness was also compared. RESULTS: At 6 months after treatment, 45 (64.3%) patients receiving high dose and 59 (78.7%) patients receiving low dose were hyperthyroidism. Clinical outcome at one year showed persistence of hyperthyroidism in 21 (30%) patients of the high dose regimen and 36 (48%) patients of the low dose regimen. At one year post treatment, it was demonstrated that the high dose regimen could eliminate hyperthyroidism in a significantly shorter time than the low dose regimen, i.e., 259.6 days and 305.5 days, respectively, p = 0.008). For the persistent hyperthyroid patients, the average total cost of treatment in the low dose group was significantly higher than that of the high dose group, i.e., 13,422.78 baht and 10,942.79 baht, respectively; p = 0.050). CONCLUSION: A high dose regimen of radioactive iodine treatment is more effective than the low dose regimen. The successful outcome of a high dose regimen occurred significantly earlier than that of the low dose regimen. For the persistent hyperthyroid patients, the average total cost in the low dose group was significantly higher than that of the high dose group.

Factors affecting standardized uptake value (SUV) of positron emission tomography (PET) imaging with l8F-FDG.

OBJECTIVE: The purpose of the study was to study factors affecting SUV of PET imaging with 18F-FDG. MATERIAL AND METHOD: PET/CT Biograph 64 was used to acquire the data. A NEMA PET phantom with 6 spheres varying in diameter from 10 to 37 mm was used to mimic the human body and tumors. Background activity of 18F in the phantom was 0.14 microCi/ml and tumor-to-background ratios (TBR) of 2:1, 5:1 and 10:1 were studied. For each TBR, thirty sinograms were acquired with 3-min scan durations. Different scan durations varying from 3 to 20 min using a TBR of 5:1 were studied and three datasets of each scan time were collected Sinograms were reconstructed using the Ordered Subset Expectation Maximization (OSEM) algorithm with 5 mm Full-Width-at-Half-Maximum (FWHM) Gaussian filtering. Sinograms at TBR of 5:1 were reconstructed by varying the number of iterative updates of OSEM (N) from 8 to 168 and SUVavg and SUVmax were measured. The percentage of underestimation of SUVs was used to study the effect of tumor size and TBR. Intraclass correlation coefficient (ICC) was used to test the reliability of SUVmax with different scan durations. RESULTS: The results showed that both the SUVavg and SUVmax rapidly increased when N was <48 and slightly increased afterwards. At TBRs ranging from 2:l to 10:1, the percentages of underestimation of SUVmax ranged from 8.17 to 22.46 and that of SUVavg were ranged from 41.44 to 52.33 for 37-mm sphere and from 40.38 to 54.52 and from 48.97 to 67.73 for 10-mm sphere respectively. Different scan durations gave reliable SUVs(max) with ICC of 0.996. CONCLUSION: SUVs increased as N increased The percentage of underestimation of the SUV depended on tumor size and TBR. Scan duration did not affect SUVs.

International Atomic Energy Agency-sponsored multination study of intra-arterial rhenium-188-labeled lipiodol in the treatment of inoperable hepatocellular carcinoma: results with special emphasis on prognostic value of dosimetric study.

A multicenter study was sponsored by the International Atomic Energy Agency (IAEA) to assess the safety and efficacy of transarterial rhenium-188 ((188)Re) HDD lipiodol (radioconjugate to lipiodol using an HDD kit) in the treatment of unresectable hepatocellular carcinoma. During 5 years, 185 patients received at least 1 treatment of radioconjugate, and 51 were retreated. The level of radioconjugate administered was based on radiation-absorbed dose to critical normal organs, calculated after a "scout" dose of radioconjugate. The total injected activity, including the scout dose during the first treatment, ranged from 21 to 364 mCi (mean, 108 mCi/4 GBq). Immediate and late side-effects were minimal. Tumor size could be evaluated in 88 patients. Among these patients, the objective response rate was 25%; stable disease was observed in 53% and tumor progression in 22%. With a median follow-up of 455 days, the estimated 12- and 24-month overall survival was 46% and 23%. This multicenter study shows that (188)Re lipiodol is a safe and cost-effective method to treat primary hepatocellular carcinoma via the transarterial route and requires further evaluation by treatment of greater numbers of patients.

Treatment outcome of Graves' disease in Thai children.

BACKGROUND: Graves' disease is the most common cause of thyrotoxicosis in children. Treatment of Graves' disease consists of anti-thyroid drugs, radioactive iodide and thyroidectomy but the optimal treatment of GD in children is still controversial. OBJECTIVE: To review treatment outcome of Graves' disease in Thai children. MATERIAL AND METHOD: Retrospective review of 32 children with Graves' disease, diagnosed between Jan. 1994 and Dec. 2004, at the Division of Pediatric Endocrinology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand was performed. RESULTS: All patients (median age 10.5 yrs, range 2.85-15 yrs) presented with goiter and increased serum T4 (median 18.4 mcg/dL, range 8.8-30 mcg/dL), serum T3 (median 443 ng/dL, range 206-800 ng/dL) and suppressed TSH levels (median 0.009 mU/L, range 0-0.18 mU/L). Anti-thyroglobulin and Anti-microsomal antibodies were positive in 70% and 82% respectively. All patients except two were initially treated with propylthiouracil (PTU). Two patients were initially treated with methimazole. Adverse reaction of PTU occurred in two patients (One girl had arthralgia, positive pANCA, nephritis and another girl had skin rash and arthralgia). Clinical course of 32 patients after treatment with anti-thyroid drugs mainly PTU for 3.4 (range 0.3-11.2) years is as follows: six (18.8%) underwent remission (cessation of PTU > 2 yrs), three (9.4%) relapsed, one (3.1%) underwent subtotal thyroidectomy, and seven (21.9%) had I131 treatment. All patients (6 of 7) who received I131 dose of 100 microCi/g of thyroid tissue required more than a single dose of I131 treatment. Further outcome in fifteen patients (46.9%) is yet to be followed. Among these patients PTU was just discontinued in four and eleven had never been off anti-thyroid drugs (four still had biochemical hyperthyroidism and seven were biochemically euthyroid). CONCLUSION: PTU was the most common first line therapy in the presented patients with Graves' disease. Remission rate was only 18.8% after an average 3.5 years of treatment with anti-thyroid drugs. I131 or thyroidectomy was used as second line therapy in the present study. They were offered to those who developed side effects, had poor compliance or failed medication. For those who received I131, higher dose (200 microCi/g of thyroid tissue) seemed to be more effective than the lower dose (100 microCi/g).

Intra-arterial rhenium-188 lipiodol in the treatment of inoperable hepatocellular carcinoma: results of an IAEA-sponsored multination study.

PURPOSE: Intra-arterial injections (IAI) of 131I-lipiodol is effective in treating hepatocellular carcinoma patients, but is expensive and requires a 7-day hospitalization in a radioprotection room. 188Re is inexpensive, requires no patient isolation, and can be used with lipiodol. METHODS AND MATERIALS: This International Atomic Energy Agency-sponsored phase II trial aimed to assess the safety and the efficacy of a radioconjugate 188Re + lipiodol (188Re-Lip) in a large cohort of hepatocellular carcinoma patients from developing countries. A scout dose is used to determine the maximal tolerated dose (lungs <12 Gy, normal liver <30 Gy, bone marrow <1.5 Gy) and then the delivery of the calculated activity. Efficacy was assessed using response evaluation criteria in solid tumor (RECIST) and alpha-feto-protein (alpha FP) levels and severe adverse events were graded using the Common Toxicity Criteria of the National Cancer Institute scale v2.0. RESULTS: The trial included 185 patients from eight countries. The procedure was feasible in all participating centers. One treatment was given to 134 patients; 42, 8, and 1 received two, three, and four injections, respectively. The injected activity during the first treatment was 100 mCi. Tolerance was excellent. We observed three complete responses and 19 partial responses (22% of evaluable patients, 95% confidence interval 16-35%); 1- and 2-year survivals were 46% and 23%. Some factors affected survival: country of origin, existence of a cirrhosis, Cancer of the Liver Italian Program score, tumor dose, absence of progression, and posttreatment decrease in alpha FP level. CONCLUSIONS: IAI of 188Re-Lip in developing countries is feasible, safe, cost-effective, and deserves a phase III trial.