Evaluation of ablation of thyroid remnants with 1850 MBq iodine-131 in 67 patients with thyroid cancer.

BACKGROUND: Radioiodine remnant ablation (RRA) is used to destroy residual normal thyroid tissue after total thyroidectomy in differentiated thyroid carcinoma (DTC) patients. As 1850-MBq RRA is routinely performed at our facility, we evaluated the outcomes. METHODS: Sixty-seven DTC patients without macroscopic residual lesions after total thyroidectomy were evaluated. Thyroglobulin (Tg) was measured 2-3 months before RRA with thyroxin administration (pretreatment); just before ablation after a 3-week iodine intake restriction with thyroxin withdrawal (THW) (N.=16) or recombinant human thyroid-stimulating hormone (rhTSH) stimulation (N.=51); and 3 months after RRA, after a 2-week iodine intake restriction and 3-week THW (N.=57) or rhTSH stimulation (N.=10). All patients received 131I (1850 MBq) treatment followed by 131I scintigraphy about 8 days later (8.18±0.91) and 131I scintigraphy (185 MBq) after the dosage 24 hours later 3months after RRA. Initial RRA goal was defined as negatively visible uptake in 131I thyroid bed (VUT) and a Tg level of <2 ng/mL 3 months after RRA. RESULTS: Rest 60 patients whose TSH levels were below 0.5 µIU/mL of all 67 patients were evaluated. Negatively VUT on 3 months after RRA was shown in 56 out of 60 patients (93.3%). Initial RRA goal was achieved in 21 (42.0%) of 50 patients, excluding 3 patients whose Tg levels 3 months after RRA were not measured and 7 patients with anti-Tg antibodies. Pretreatment Tg levels (P=0.0003) was significant predictive factor for Initial RRA goal on multivariate logistic regression analysis. CONCLUSIONS: RRA with 1850 MBq is effective by visual diagnosis, about 40% of all intermediate or high-risk DTC patients achieved initial RRA goals by both visual and Tg levels diagnosis.

Prognostic significance of pretreatment 18F-fluorodeoxyglucose positron emission tomography evaluation using metabolic tumor volume of the primary tumor and lymph nodes in advanced hypopharyngeal cancer.

BACKGROUND: The purpose of this study was to retrospectively evaluate the usefulness of pretreatment positron emission tomography (PET) using metabolic tumor volume (MTV) of the primary tumor and lymph nodes in advanced hypopharyngeal cancer. METHODS: From June 2007 to December 2015, consecutive patients with advanced hypopharyngeal cancer who underwent PET and were treated with definitive radiation therapy were retrospectively reviewed. RESULTS: A total of 61 patients were eligible for this study. On multivariate analysis, MTV of the primary tumor (MTV-T) was significantly related to the local control rate and overall survival (OS) (P = .036 and .012, respectively). In patients with lower MTV-T, MTV of metastatic lymph nodes (MTV-N) was significantly related to disease-specific survival and OS (P = .012 and .017, respectively). CONCLUSION: MTV-T is a significant predictor in patients with advanced hypopharyngeal cancer, and MTV-N is also significant in patients with lower MTV-T.

Regional Liver Disorder with Differences in the Accumulation of 99mTc-phytate and 99mTc-galactosyl Human Serum Albumin.

We report a 56-year-old woman with regional liver disorder due to acute hepatitis. Computed tomographic images showed low signal density at a plain phase and prolonged contrast effect at a late phase in the left hepatic lobe, in which an accumulation of 99mTc-phytate increased, whereas that of 99mTc-galactosyl human serum albumin (GSA) decreased. Meanwhile, in the right lobe, an accumulation of 99mTc-GSA showed more increased than that of 99mTc-phytate. Liver biopsy showed massive hepatocyte necrosis and interface hepatitis in the left lobe, and moderate hepatitis in the right lobe. Differences in the accumulation between these scintigrams were helpful for understanding rapid necrosis in the left lobe, resulting in a compensatory enlargement of the right lobe. Clinicians should be aware that some cases of acute hepatitis cause regional liver disorder although most cases show homogeneous inflammation.

Usefulness of Stereotactic Radiotherapy Using CyberKnife for Recurrent Lymph Node Metastasis of Differentiated Thyroid Cancer.

A woman in her 60s presented with a recurrent lymph node metastasis from a papillary thyroid carcinoma in the right parapharyngeal space. She had already undergone total thyroidectomy, five resections for cervical lymph node metastases, and right carotid rebuilding. Surgical resection of the current metastasis was impossible. 131I-radioiodine therapy (RIT) with 3.7 GBq 131I was not effective; therefore, stereotactic radiation therapy (SRT) using a CyberKnife radiotherapy system was scheduled. The prescription dose was 21 Gy, and a dose covering 95% of the planning target volume (PTV) in three fractions was administered. The PTV was 4,790 mm3. Follow-up magnetic resonance imaging conducted 3 and 12 months after the SRT demonstrated a remarkable and gradual reduction of the recurrent lymph node metastasis in the right parapharyngeal space and no evidence of recurrence. For multidisciplinary therapy of unresectable and/or RIT unresponsive locoregional lymph node metastases and recurrences of DTC, SRT using the CyberKnife system should be considered.

[Imaging of hyperparathyroidism-Ultrasonography and 99mTc-MIBI scintigraphy-].

Treatments for primary hyperparathyroidism due to adenoma, hyperplasia and carcinoma and secondary hyperparathyroidism are mainly surgical resections of them. Accurate imaging diagnoses of the existences and the regions are very important for reductions of invasiveness. We describe ultrasonography and (99m)Tc-MIBI scintigraphy of hyperparathyroidism. We explain an advantage, a disadvantage and diagnosability of these modalities. We mention utilities of SPECT/CT, too. We show echogram and (99m)Tc-MIBI scintigraphy images about 3 cases of hyperparathyroidism.

Usefulness of standardized uptake value normalized by individual CT-based lean body mass in application of PET response criteria in solid tumors (PERCIST).

Our aim in this study was to verify the usefulness of the standardized uptake value (SUV) normalized by individual CT-based lean body mass (LBMCT) in application of PET response criteria in solid tumors (PERCIST).We retrospectively investigated 14 patients (4 male and 10 female) with malignant lymphoma who were undergoing chemotherapy. (18)F-FDG PET/CT examinations were performed before and after chemotherapy. The LBMCT was calculated by estimation of fat weight from CT data (from skull base to pelvis). The mean ± standard deviation (SD) and the Bland-Altman plot were used for comparison among body weight, LBMCT, and LBM derived from a predictive equation (LBMPE). Indices for FDG uptake in the liver were: SUV, SUV based on LBMPE (SULPE), and SUV based on LBMCT (SULCT). Overall differences between the uptake values were analyzed by one-way ANOVA. If the ANOVA showed significance, differences between uptake values were investigated further by use of the Tukey-Kramer test. The mean values of body weight, LBMPE, and LBMCT were: 55.4 ± 14.9 (39.0-112.0), 43.0 ± 10.5 (31.3-75.2), and 35.3 ± 9.8 (23.4-75.8) kg, respectively. There was a wide dispersion between LBMPE and LBMCT (differences, 7.6 ± 3.6 kg; 95 % CI, 6.42-8.85). LBMPE was higher than LBMCT in all the cases except in Case 11. The mean uptake values significantly differed among SUV, SULPE, and SULCT (F = 68.3, p < 0.05). Whereas SULPE deviated from PERCIST criteria in seven patients, SULCT satisfied the criteria except in one case. These results suggest that liver SULCT is useful for application of PERCIST.

Comprehensive Screening of Gene Function and Networks by DNA Microarray Analysis in Japanese Patients with Idiopathic Portal Hypertension.

The functions of genes involved in idiopathic portal hypertension (IPH) remain unidentified. The present study was undertaken to identify the functions of genes expressed in blood samples from patients with IPH through comprehensive analysis of gene expression using DNA microarrays. The data were compared with data from healthy individuals to explore the functions of genes showing increased or decreased expression in patients with IPH. In cluster analysis, no dominant probe group was shown to differ between patients with IPH and healthy controls. In functional annotation analysis using the Database for Annotation Visualization and Integrated Discovery tool, clusters showing dysfunction in patients with IPH involved gene terms related to the immune system. Analysis using network-based pathways revealed decreased expression of adenosine deaminase, ectonucleoside triphosphate diphosphohydrolase 4, ATP-binding cassette, subfamily C, member 1, transforming growth factor-ß, and prostaglandin E receptor 2; increased expression of cytochrome P450, family 4, subfamily F, polypeptide 3, and glutathione peroxidase 3; and abnormalities in the immune system, nucleic acid metabolism, arachidonic acid/leukotriene pathways, and biological processes. These results suggested that IPH involved compromised function of immunocompetent cells and that such dysfunction may be associated with abnormalities in nucleic acid metabolism and arachidonic acid/leukotriene-related synthesis/metabolism.

131I abnormal uptake by the thyroid bed from Zuckerkandl tubercle diagnosis by 131I SPECT/CT.

After thyroid remnant ablation following total thyroidectomy for thyroid cancer, 131I SPECT/CT revealed 131I uptake, regarded as thyroid bed uptake on planar images, in the anterior cervical region. On SPECT/CT, the 131I uptake focus appeared at the esophagus, suggesting esophageal invasion. No esophageal invasion had been recognized intraoperatively, and no residual uptake was detected by 131I scintigraphy evaluating therapeutic effects 3 months after ablation. Preoperative CT revealed a retrotracheal space portion extending from the normal thyroid with the same density, suggesting Zuckerkandl tubercle. Abnormal uptake on SPECT/CT was deemed Zuckerkandl tubercle-derived thyroid bed uptake.

Survey of survival among patients with hepatitis C virus-related hepatocellular carcinoma treated with peretinoin, an acyclic retinoid, after the completion of a randomized, placebo-controlled trial.

BACKGROUND: This study examined the effects of peretinoin, an acyclic retinoid, on the survival of patients with hepatitis C virus-related hepatocellular carcinoma (HCC) who had completed curative therapy and participated in a randomized, placebo-controlled trial. METHODS: This study was an investigator-initiated retrospective cohort study. Subjects were all patients who were administered the investigational drug (peretinoin 600 mg/day, peretinoin 300 mg/day, or placebo) in the randomized trial. Survivals between the groups were compared using the log-rank test, and hazard ratios were estimated by Cox regression. RESULTS: Survey data were collected from all patients (n = 392) who participated in the randomized trial, all of whom were then divided into the peretinoin 600 mg/day (n = 132), peretinoin 300 mg/day (n = 131), and placebo (n = 129) groups. At the median follow-up of 4.9 years, 5-year cumulative survival rates for patients in the 600 mg/day, 300 mg/day, and placebo groups were 73.9, 56.8, and 64.3 %, respectively. Comparison of overall survival among patients classified as Child-Pugh A revealed that survival of the 600 mg/day group (n = 105) was significantly longer than that of the placebo group (n = 108) (hazard ratio 0.575, 95 % CI 0.341-0.967; P = 0.0347). CONCLUSIONS: Administration of 600 mg/day peretinoin to patients with hepatitis C virus-related HCC who have completed curative therapy may improve survival for those classified as Child-Pugh A, for whom liver function is relatively stable.

Peretinoin after curative therapy of hepatitis C-related hepatocellular carcinoma: a randomized double-blind placebo-controlled study.

BACKGROUND: Effective prophylactic therapies have not been established for hepatocellular carcinoma recurrence. Peretinoin represents one novel option for patients with hepatitis C virus-related hepatocellular carcinoma (HCV-HCC), and it was tested in a multicenter, randomized, double-blind, placebo-controlled study. METHODS: Patients with curative therapy were assigned to one of the following regimens: peretinoin 600, 300 mg/day, or placebo for up to 96 weeks. The primary outcome was recurrence-free survival (RFS). RESULTS: Of the 401 patients initially enrolled, 377 patients were analyzed for efficacy. The RFS rates in the 600-mg group, the 300-mg group, and the placebo group were 71.9, 63.6, and 66.0 % at 1 year, and 43.7, 24.9, and 29.3 % at 3 years, respectively. The primary comparison of peretinoin (300 and 600-mg) with placebo was not significant (P = 0.434). The dose-response relationship based on the hypothesis that "efficacy begins to increase at 600 mg/day" was significant (P = 0.023, multiplicity-adjusted P = 0.048). The hazard ratios for RFS in the 600-mg group vs. the placebo group were 0.73 [95 % confidence interval (CI) 0.51-1.03] for the entire study period and 0.27 (95 % CI 0.07-0.96) after 2 years of the randomization. Common adverse events included ascites, increased blood pressure, headache, presence of urine albumin, and increased transaminases. CONCLUSIONS: Although the superiority of peretinoin to placebo could not be validated, 600 mg/day was shown to be the optimal dose, and treatment may possibly reduce the recurrence of HCV-HCC, particularly after 2 years. The efficacy and safety of peretinoin 600 mg/day should continue to be evaluated in further studies.

Positioning of 18F-fluorodeoxyglucose-positron emission tomography imaging in the management algorithm of hepatocellular carcinoma.

BACKGROUND AND AIM: (18) F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) may detect primary lesions (PLs) and extrahepatic metastases (EHMs) only in advanced hepatocellular carcinoma (HCC) patients. We investigated the requirement of PET and the optimal timing of PET scanning for accurate staging and treatment planning. METHODS: We conducted a retrospective investigation of 64 HCC patients who underwent PET (median age, 74 years; male/female, 41/23; etiology, 46 hepatitis C virus/4 hepatitis B virus/4 alcoholic/10 others). To determine the best timing for PET examinations, we analyzed PET result-based recommended treatment changes and characteristics of patients with FDG-avid PLs or EHMs. RESULTS: FDG-avid PLs were detected by PET in 22 patients (34%): 18 with hypervascular PL, 11 with serum α-fetoprotein levels ≥ 200 ng/mL, and 11 beyond Milan criteria. EHMs were detected in 21 patients (33%: lymph nodes, 8; lung, 5; abdominal wall, 4; bone, 3; other organs, 4 [including overlapping]). Recommended treatments changed for 16 patients (25%) because of Barcelona Clinic Liver Cancer stage increases based on PET scanning. In multivariate analyses, serum α-fetoprotein levels ≥ 200 ng/mL and beyond Milan criteria were independent factors for FDG-avid PLs and a maximum standardized uptake value (SUVmax) of PLs of ≥ 4.0 was an independent factor for FDG-avid EHMs (P = 0.002, 0.008, and 0.045, respectively). CONCLUSIONS: PET allows detection of HCC spread in patients with elevated serum α-fetoprotein levels or those beyond Milan criteria and detects EHMs in patients with PLs with high SUVmax values. Optimally timed PET scans can complement conventional imaging for accurate staging and treatment strategy determination.

Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An ¹¹C-(R)-PK11195 PET Study.

UNLABELLED: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disease characterized by chronic, profound, disabling, and unexplained fatigue. Although it is hypothesized that brain inflammation is involved in the pathophysiology of CFS/ME, there is no direct evidence of neuroinflammation in patients with CFS/ME. Activation of microglia or astrocytes is related to neuroinflammation. (11)C-(R)-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carboxamide ((11)C-(R)-PK11195) is a ligand of PET for a translocator protein that is expressed by activated microglia or astrocytes. We used (11)C-(R)-PK11195 and PET to investigate the existence of neuroinflammation in CFS/ME patients. METHODS: Nine CFS/ME patients and 10 healthy controls underwent (11)C-(R)-PK11195 PET and completed questionnaires about fatigue, fatigue sensation, cognitive impairments, pain, and depression. To measure the density of translocator protein, nondisplaceable binding potential (BP(ND)) values were determined using linear graphical analysis with the cerebellum as a reference region. RESULTS: The BP(ND) values of (11)C-(R)-PK11195 in the cingulate cortex, hippocampus, amygdala, thalamus, midbrain, and pons were 45%-199% higher in CFS/ME patients than in healthy controls. In CFS/ME patients, the BP(ND) values of (11)C-(R)-PK11195 in the amygdala, thalamus, and midbrain positively correlated with cognitive impairment score, the BP(ND) values in the cingulate cortex and thalamus positively correlated with pain score, and the BP(ND) value in the hippocampus positively correlated with depression score. CONCLUSION: Neuroinflammation is present in widespread brain areas in CFS/ME patients and was associated with the severity of neuropsychologic symptoms. Evaluation of neuroinflammation in CFS/ME patients may be essential for understanding the core pathophysiology and for developing objective diagnostic criteria and effective medical treatments.

Usefulness of three-phase bone scintigraphy and SPECT/CT for the diagnosis of bone lesions of systemic sarcoidosis.

We report a three-phase bone scintigraphy for the diagnosis of a peripheral bone lesion caused by systemic sarcoidosis. A 32-year-old man with suspected osteomyelitis of the right forefinger underwent three-phase bone scintigraphy with Tc-99m hydroxymethylene diphosphonate (HMDP) and single-photon emission computed tomography/computed tomography (SPECT/CT). The lesion was rich in blood flow according to flow study and blood pool study on bone scintigraphy, and was associated with an osteolytic change on SPECT/CT imaging performed 3 hours after injection of a radioisotope (RI). Whole-body bone scintigraphy indicated multiple high levels of abnormal RI accumulation. The findings of the three-phase bone scintigraphy and SPECT/CT suggested the presence of systemic sarcoidosis; however, a subsequent (18)F-fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT) could not exclude the possibility of multiple metastases from testicular tumors. Therefore, testicular enucleation was performed, and the pathological examination confirmed the presence of sarcoidosis.

[Clinical nuclear medicine in bone metastases].

(99m)Tc-hydroxymethylene diphosphonate is not directly to Calcium of the bone matrix, but is binding to hydroxyapatite within the bone matrix. Strontium-89 is a member of family II A of the periodic table, same as Calcium, and is incorporated into bone matrix directly. It is very important that the the regions of the pain from bone metastases are present in the site of the abnormal uptake by bone metastases.

Subcutaneous Extravasation of Sr-89: Usefulness of Bremsstrahlung Imaging in Confirming Sr-89 Extravasation and in the Decision Making for the Choice of Treatment Strategies for Local Radiation Injuries Caused by Sr-89 Extravasation.

A male patient in his 20s presented at our clinic with pain caused by bone metastases of the primitive neuroectodermal tumor, and Sr-89 was administrated to palliate the pain. After receiving the injection, the patient complained of a slight burning pain at the catheterized area. Slight reddening and small circular swelling (diameter, 0.5 cm) were observed at the catheterized area. Sr-89 extravasation was suspected. To estimate the amount of subcutaneous Sr-89 leakage, bremsstrahlung imaging was immediately performed. We speculated that the skin-absorbed dose from subcutaneous infiltration of Sr-89 was 1.78 Gy. The mildest clinical sign of local radiation injury was erythema. The received dose was higher than 3 Gy, and the time of onset was from 2 to 3 weeks. In our patient, local radiation injuries (LRIs) did not occur. Though requiring further verification, subsequent bremsstrahlung imaging and estimation of the skin-absorbed dose from the subcutaneous infiltration of Sr-89 are useful in confirming Sr-89 extravasation and in the decision making for the choice of treatment strategies for LRIs caused by Sr-89 extravasation.

PET imaging-based evaluation of hepatobiliary transport in humans with (15R)-11C-TIC-Me.

UNLABELLED: It is well accepted that drug transporters play a pivotal role in hepatobiliary excretion of anionic drugs, in which drug-drug interactions and genetic polymorphisms are known to cause variations. However, PET probes for in vivo functional characterization of these transporters have not been established yet. We used PET to investigate hepatic uptake and subsequent canalicular efflux of (11)C-labeled (15R)-16-m-tolyl-17,18,19,20-tetranorisocarbacyclin methyl ester [(15R)-(11)C-TIC-Me)] in healthy subjects. METHODS: Serial PET scans of the abdominal region in healthy male subjects were obtained with or without the organic anion-transporting polypeptide (OATP) inhibitor rifampicin after intravenous injection of (15R)-(11)C-TIC-Me as a radiotracer. Venous blood samples and PET images were obtained at frequent intervals up to 30 min after administration of the PET tracer. Dynamic imaging data were evaluated by integration plots of data collected for 2-10 min and for 10-30 min after tracer administration for the determination of tissue uptake clearance and biliary efflux clearance, respectively. RESULTS: After rapid hydrolysis in blood, the acid form-(11)C-labeled (15R)-16-m-tolyl-17,18,19,20-tetranorisocarbacyclin [(15R)-(11)C-TIC]-accumulated in the liver (37% of the dose by 17 min), and the radioactivity was then excreted into the bile (6.2% by 30 min). Rifampicin (600 mg by mouth), a potent OATP inhibitor, significantly reduced the radioactivity excreted into the bile (by 44%) by inhibiting both uptake (by 45%) and subsequent canalicular efflux (by 62%). (15R)-(11)C-TIC is an in vitro substrate of OATP1B1 and OATP1B3, and clinically relevant concentrations of rifampicin inhibited uptake by OATP1B1 and OATP1B3. These results demonstrated that in humans, (15R)-(11)C-TIC-associated radioactivity is excreted into the bile by organic anion transport systems. CONCLUSION: We demonstrated that PET image analysis with (15R)-(11)C-TIC-Me is useful for investigating variations in OATP function in the human hepatobiliary transport system.

The role of FDG PET-CT in the therapeutic evaluation for HNSCC patients.

F-18 FDG PET/CT has been widely used to diagnose primary tumors and lymph node metastases and to evaluate the response of head and neck squamous cell carcinoma (HNSCC) to therapy. The advantage of using PET/CT is that this combination allows metabolic information to be precisely overlapped with anatomical information, thereby improving the identification of sites with an abnormal accumulation of F-18 FDG. The role of FDG PET/CT in the therapeutic evaluation (such as in treatment planning, the therapeutic response, and the surveillance and examination of HNSCC patients) is discussed in this manuscript. When evaluating the post-treatment outcome via FDG PET/CT, it is important to exclude the post-treatment inflammation-related increase in glucose metabolism in lymph nodes, salivary gland, muscles, and soft tissues. The influence of inflammation can be eliminated if PET/CT is performed after 12 weeks, by which time post-treatment inflammation subsides. Further, FDG PET/CT affords a high negative predictive value. Based on the results of an FDG PET/CT test, some invasive tests that are performed to detect recurrence can be omitted.

Lymphoscintigraphy with single-photon emission computed tomography/computed tomography is useful for determining the site of chyle leakage after esophagectomy.

We describe the case of chylothorax after esophagectomy for esophageal carcinoma. Lymphoscintigraphy with Tc-99m-human serum albumin-diethylenetriaminepentaacetic acid showed an abnormal radioisotope accumulation on the left side of the thoracic duct. Single-photon emission computed tomography (SPECT) combined with computed tomography (CT) revealed a hot spot directly on the site at, which the thoracic duct was ligated during surgery, which was the suggested site of chyle leakage. We emphasize that lymphoscintigraphy with SPECT/CT is very useful tool for accurately identifying the site of the chyle leakage.