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author:("Ryu, Jin-took")
1.  18F-FDG PET in Patients with Primary Systemic Anaplastic Large Cell Lymphoma: Differential Features According to Expression of Anaplastic Lymphoma Kinase 
Primary systemic anaplastic large cell lymphoma (ALCL) is divided into two entities according to the expression of anaplastic lymphoma kinase (ALK). We investigated 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) findings in primary systemic ALCL according to ALK expression.
Thirty-seven patients who had baseline PET before CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone)-based chemotherapy were enrolled. Among them, patients who underwent interim and/or post-therapy PET were further investigated for the treatment response and survival analysis. Baseline PET was analyzed visually and semi-quantitatively using peakSUV, and interim and post-therapy PETs were visually analyzed.
All cases were 18F-FDG-avid on baseline PET. The peakSUV of ALK-positive ALCL (n = 16, 18.7 ± 10.5) was higher than that of ALK-negative ALCL (n = 21, 10.0 ± 4.9) (P = 0.006). In ALK-negative ALCL, complete response (CR) rate in negative-interim PET was higher than positive-interim PET (100 % vs 37.5 %, P = 0.02); however, there was no such difference in ALK-positive ALCL (100 % vs 75 %, P = 0.19). The 3-year progression-free survival (PFS) was not significantly different between ALK-positive and ALK-negative ALCL (72.7 % vs 47.6 %, P = 0.34). In ALK-negative ALCL, negative interim and post-therapy PET patients had better 3-year PFS than positive interim (83.3 % vs 25.0 %, P = 0.06) and post-therapy PET patients (70.0 % vs 20.0 %, P = 0.04). In contrast, ALK-positive ALCL had no such differences between PFS and PET results.
On baseline PET, all cases showed 18F-FDG-avidity, and ALK expression was related to higher 18F-FDG uptake. ALK-positive patients tend to have better PFS than ALK-negative patients. Negative-interim PET was a good indicator of CR, and interim or post-therapy PET was helpful for predicting the prognosis only in the ALK-negative group.
PMCID: PMC4035167  PMID: 24900120
Primary systemic anaplastic large cell lymphoma; Anaplastic lymphoma kinase; 18F-FDG PET
2.  An Unusual Case of Anaphylaxis After Fluorine-18-Labeled Fluorodeoxyglucose Injection 
[18F]FDG (fluorine-18 fluoro-2-deoxy-D-glucose) positron emission tomography (PET) is used worldwide for oncologic and neurologic applications. To date, the potential harm caused by [18F]FDG has focused on its radiation exposure effects rather than on its pharmacological effects. While an allergic response in the form of a skin manifestation has been reported after exposure to [18F]FDG, this report describes the first case of hypotension following exposure to this tracer. Here, the development of anaphylaxis after [18F]FDG injection is described.
PMCID: PMC4035188  PMID: 24900108
FDG; Anaphylaxis; Allergic
3.  Long-Term Consequence of Elevated Thyroglobulin in Differentiated Thyroid Cancer 
Thyroid  2013;23(1):58-63.
Serum thyroglobulin (Tg) is the most sensitive biomarker for recurrence of differentiated thyroid cancer (DTC). We have assessed the changing pattern of stimulated Tg (sTg) and the clinical course of patients with no structural evidence of disease (NSED), based on imaging studies such as neck ultrasonography (US), fluorodeoxyglucose positron emission tomography, and/or chest computed tomogram (CT). We sought to determine if, in patients with DTC who had been treated with bilateral thyroidectomy and remnant ablation with radioactive iodine, sTg 1 year (sTg1) after initial treatment and repeated sTg measurements, 1–2 years after sTg1, helped predict the long-term outcome with respect to structural recurrence and biochemical remission (BR), which is defined as sTg <1 ng/mL.
We retrospectively assessed the records of patients with DTC who had been treated with bilateral thyroidectomy and remnant ablation with radioactive iodine between 1995 and 2004. The study included 186 patients who had NSED with sTg1 ≥2 ng/mL and subsequent sTg measurements (sTg2) without additional treatment. Patients were classified into three groups based on their sTg1 measurements: Group A, 2–4.9 ng/mL; Group B, 5–19.9 ng/mL; and Group C, ≥20 ng/mL. Patients were also classified into two groups based on whether sTg2, 1–2 years after sTg1, had decreased by ≥50% (Group 1) or had either decreased by <50% or increased (Group 2). sTg was measured every 1–2 years until structural recurrence or BR.
Patients remaining in NSED showed a decrease in serial sTg. Of patients in Groups A, B, and C, 41%, 17%, and 1%, respectively, achieved BR, and there was a significant difference in the BR rate between Groups 1 and 2 (p<0.001). In patients with structural recurrence, serial sTg generally did not decrease from sTg1. There was a significant difference in the recurrence rate among Groups A, B, and C (p=0.005) and between Groups 1 and 2 (p<0.001).
We found that 41% of patients with sTg1 in the range 2–5 ng/mL achieved BR, and that sTg1 and percent change of subsequent sTg were predictive of BR. Repeated sTg measurements are useful for predicting patient prognosis in patients with DTC.
PMCID: PMC3539255  PMID: 22973946
4.  Long-Term Clinical Outcome of Differentiated Thyroid Cancer Patients with Undetectable Stimulated Thyroglobulin Level One Year After Initial Treatment 
Thyroid  2012;22(8):784-790.
Measurement of the serum thyroglobulin (Tg) level with TSH stimulation (sTg) is the cornerstone of monitoring for the recurrence or persistence of differentiated thyroid cancer (DTC) in patients who have undergone surgery and remnant ablation. However, there have been several reports that an undetectable sTg could not predict the absence of future recurrence. The aim of this study was to evaluate the long-term outcome of DTC patients who achieved biochemical remission (BR, defined as sTg<1 ng/mL) after initial treatment, and to determine the role of repeated sTg measurement in detecting a clinical recurrence.
This is a retrospective observational cohort study in a tertiary referral hospital. There were 1010 DTC patients who achieved BR at 12 months after the initial treatment (surgery and ablation), and they were eligible for analysis. Among them, 787 patients had values of repeated sTg.
Thirteen out of 1010 (1.3%) patients had clinical recurrences during a median 84 months of follow-up. All of the clinical recurrences were limited to the cervical lymph nodes without clinical evidence of distant metastasis. Among 787 patients with available repeated sTg, 10 had clinical recurrences (5 out of 750 patients with repeated sTg<1 ng/mL and 5 out of 37 patients with repeated sTg≥1 ng/mL). Patients with repeated sTg ≥1 ng/mL had a much greater chance of disease recurrence (log-rank statistics=43.7, df=1, p<0.001).
About 1% of DTC patients who had sTg<1 ng/mL 12 months after initial treatment had a clinical recurrence. All of clinical recurrences were loco-regional recurrences. Although repeated sTg measurement can be helpful to predict recurrence, we could not recommend it for surveillance in patients with BR due to its very low yield.
PMCID: PMC3407383  PMID: 22780573
5.  A Case of Acute Q Fever Hepatitis Diagnosed by F-18 FDG PET/CT 
A 53-year-old man with fever of unknown origin underwent F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) as a workup for a fever of unknown origin. On presentation, he complained of fever, chills, and myalgia. The F-18 FDG PET/CT scan showed diffusely increased uptake of the liver with mild hepatomegaly. A liver biopsy then revealed fibrin-ring granulomas typically seen in Q fever. The patient was later serologically diagnosed as having acute Q fever as the titers for C. burnetii IgM and IgG were 64:1 and 16:1, respectively. He recovered completely following administration of doxycycline. This indicates that F-18 FDG PET/CT may be helpful for identifying hepatic involvement in Q fever as a cause of fever of unknown origin.
PMCID: PMC4042989  PMID: 24900046
Q fever; F-18 FDG PET/CT; Fever of unknown origin
6.  The Feasibility of 18F-Fluorothymidine PET for Prediction of Tumor Response after Induction Chemotherapy Followed by Chemoradiotherapy with S-1/Oxaliplatin in Patients with Resectable Esophageal Cancer 
The aim of this study was to determine whether 18F-fluorothymidine (FLT) PET is feasible for the early prediction of tumor response to induction chemotherapy followed by concurrent chemoradiotherapy in patients with esophageal cancer.
This study was prospectively performed as a collateral study of “randomized phase II study of preoperative concurrent chemoradiotherapy with or without induction chemotherapy with S-1/oxaliplatin in patients with resectable esophageal cancer”. 18F-FLT positron emission tomography (PET) images were obtained before and after two cycles of induction chemotherapy, and the percent change of maximum standardized uptake value (SUVmax) was calculated. All patients underwent esophagography, gastrofiberoscopy, endoscopic ultrasonography (EUS), computed tomography (CT) and 18F-fluorodeoxyglucose (FDG) PET at baseline and 3–4 weeks after completion of concurrent chemoradiotherapy. Final tumor response was determined by both clinical and pathologic tumor responses after surgery.
The 13 patients for induction chemotherapy group were enrolled until interim analysis. In a primary tumor visual analysis, the tumor detection rates of baseline 18F-FLT and 18F-FDG PET were 85% and 100%, respectively. The tumor uptakes on 18F-FLT PET were lower than those of 18F-FDG PET. Among nine patients who completed second 18F-FLT PET, eight patients were responders and one patient was a non-responder in the assessment of final tumor response. The percent change of SUVmax in responders ranged from 41.2% to 79.2% (median 57.1%), whereas it was 10.2% in one non-responder.
The percent change of tumor uptake in 18F-FLT PET after induction chemotherapy might be feasible for early prediction of tumor response after induction chemotherapy and concurrent chemoradiotherapy in patients with esophageal cancer.
PMCID: PMC4042979  PMID: 24900033
18F-FLT; PET; Esophageal cancer; Induction chemotherapy; Tumor response
7.  Yttrium-90 ibritumomab tiuxetan plus busulfan, cyclophosphamide, and etoposide (BuCyE) versus BuCyE alone as a conditioning regimen for non-Hodgkin lymphoma 
The Korean Journal of Hematology  2012;47(2):119-125.
Radioimmunotherapy agents have a highly significant role in autologous stem cell transplantation as they improve tolerability and increase the efficacy of the conditioning regimen.
We retrospectively analyzed the efficacy and toxicity of yttrium-90 ibritumomab tiuxetan (Zevalin) combined with intravenous busulfan, cyclophosphamide, and etoposide (Z-BuCyE) compared with those of BuCyE alone followed by autologous stem cell transplantation in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL). The efficacy, toxicity, and engraftment characteristics were compared between 19 patients who received Z-BuCyE and 19 historical controls who received BuCyE.
The 2 treatment groups shared similar baseline characteristics. The median time to platelet engraftment (>20×109/L) and neutrophil engraftment (>0.5×109/L) did not significantly differ between the Z-BuCyE group (12 days and 10 days, respectively) and the BuCyE group (12 days and 10 days, respectively). No significant differences were observed between the groups with respect to toxicities and treatment-related mortality. The median follow-up period was 30.4 months, and median event-free survival was generally better in the Z-BuCyE group (12.5 months) vs. the BuCyE group (6.2 months, P=0.236). No significant difference in overall survival between the groups was noted.
Adding ibritumomab tiuxetan to BuCyE high-dose chemotherapy may benefit patients with relapsed or refractory B-cell NHL with no risk of additional toxicity.
PMCID: PMC3389060  PMID: 22783358
Yttrium-90 ibritumomab tiuxetan; BuCyE; Autologous stem cell transplantation; Non-Hodgkin lymphoma
8.  PET/CT Fusion Viewing Software for Use with Picture Archiving and Communication Systems 
Journal of Digital Imaging  2009;23(6):732-743.
We developed positron emission tomography (PET)/computed tomography (CT) viewing software (PETviewer) that can display co-registered PET and CT images obtained by PET/CT and stored on picture archiving and communication systems (PACS). PETviewer has tools for presetting windows for CT display; control bars for PET window level; zoom, pan, and pseudo-color functions; and allows the user to draw a rectangular region of interest (ROI) for standardized uptake value (SUV) measurement. SUV was calculated using PET DICOM header information and the pixel intensity in PETviewer. Reconstructed datasets of PET/CT and maximum intensity projection (MIP) of the PET images were transferred and archived in PACS. Phantom experiments were performed to evaluate the validity of image fusion. PET/CT images were displayed on an independent window in PACS. Transaxial PET images were reformatted as sagittal and coronal PET images, which were displayed with the corresponding CT and PET/CT fusion images with adjustable color and transparency. Transaxial, sagittal, and coronal PET images corresponding to the location of the cursor were shown using cine display of MIP images. All images were displayed in PETviewer within 20 s on a personal computer for PACS, which was equipped with a P4, 1.3-GHz CPU, and 512 Mb of RAM. We could measure maximum and mean SUV in a ROI using PETviewer. Transaxial fused images of patients and phantoms showed excellent registration and fusion of PET and CT images in the X and Y directions. PETviewer provided very useful clinical tools for assessing PET/CT images on PACS and should assist in maximizing the benefits derived from PET/CT imaging.
PMCID: PMC3046700  PMID: 19657696
PET/CT; PACS; image fusion; multimodality imaging
9.  Imaging Atherosclerosis in the Carotid Arteries with F-18-Fluoro-2-deoxy-D-glucose Positron Emission Tomography: Effect of Imaging Time after Injection on Quantitative Measurement 
To compare F-18-fluoro-2-deoxy-D-glucose (F-18 FDG) positron emission tomography/computed tomography (PET/CT) imaging at two different circulation times after injection of F-18 FDG in order to measure atherosclerosis in carotid arteries.
We assessed 12 patients with recent symptomatic plaques in the carotid arteries. F-18 FDG PET/CT carotid plaque imaging was performed for 20 min at 2 h after F-18 FDG injection in five patients and at 3 h in seven patients. We measured vessel wall uptake using the maximal standardized uptake value (SUV), and the mean and maximal blood target-to-background ratios (TBR) of the symptomatic carotid arteries. Blood pool activity (BPA) was measured as the mean SUV of the superior vena cava (SVC) and jugular vein of these 12 patients, and in 14 age- and gender-matched patients who underwent whole-body F-18 FDG PET/CT examinations 1 h after injection.
F-18 FDG PET/CT revealed visible F-18 FDG uptake in all patients with symptomatic carotid plaques. Maximal SUV did not differ between groups evaluated at 2 h and 3 h (2.62 ± 0.45 vs 3.00 ± 0.85, p = 0.335). However, mean (2.04 ± 0.22 vs 3.54 ± 0.62, p < 0.05) and maximal (1.65 ± 0.15 vs 2.70 ± 0.42, p < 0.05) TBR values that were normalized to BPA in the SVC differ significantly.
Symptomatic carotid plaques are visualized for a relatively short period of imaging time on ≥1-h PET/CT images. Quantitative parameters of atherosclerotic carotid arteries are preserved or even increased over time, whereas those of blood pools are decreased.
PMCID: PMC4042924  PMID: 24899962
F-18 FDG PET/CT; Atherosclerosis; Carotid arteries; Imaging time
10.  18F-FDG PET/CT is Useful for Pretreatment Assessment of the Histopathologic Type of Thymic Epithelial Tumors 
This study was performed to assess the usefulness of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) or PET/computed tomography (CT) for distinguishing thymic epithelial tumors according to World Health Organization (WHO) classifications.
We analyzed a total of 45 patients (range, 29–75 years of age; mean, 55 years) with pathologically confirmed thymic epithelial tumors who underwent pretreatment 18F-FDG PET or PET/CT between November 2003 and October 2009. The size, visual grading of uptake value, peak standardized uptake value (SUVpeak), uptake pattern, and contour of each tumor, and associated findings on PET or PET/CT, were analyzed relative to the three simplified WHO subgroups: less-invasive thymomas (types A and AB), more-invasive thymomas (types B1, B2, and B3) and thymic carcinomas. We statistically assessed the relationship of 18F-FDG PET or PET/CT findings with these simplified subgroups.
Of the 45 patients, ten had less-invasive thymomas, 23 had more-invasive thymomas, and 12 had thymic carcinomas. The SUVpeak of the less- and more-invasive thymomas were significantly lower than those of thymic carcinomas (p < 0.000), but there was no difference in SUVpeak between less- and more-invasive thymomas. The visual grading scale (p < 0.000), uptake pattern (p = 0.001), and contour (p < 0.000) of the tumors differed significantly among the three simplified subgroups.
The image findings of 18F-FDG PET or PET/CT differed significantly by histologic subgroups. Pre-treatment evaluation with 18F-FDG PET or PET/CT might be helpful in differentiating subgroups of thymic epithelial tumors.
PMCID: PMC4042935  PMID: 24899947
18F-fluorodeoxyglucose; PET; Thymus; Thymoma; Thymic carcinoma
11.  Prognostic parameters for recurrence of papillary thyroid microcarcinoma 
BMC Cancer  2008;8:296.
Papillary thyroid microcarcinoma (PTMC) is defined as a papillary thyroid carcinoma less than or equal to 1.0 cm in size. Independent prognostic factors for clinical recurrence of PTMC have not been clearly delineated.
Clinicopathological parameters predicting PTMC recurrence were determined by retrospective analysis of 307 patients.
Of the 293 patients eligible for analysis, 14 (5%) had recurrence during a median follow-up time of 65 months. Recurrence was observed in 8 of 166 patients (0.5%) treated with total or near-total thyroidectomy; gender (P = 0.02) and presence of lateral cervical node metastases at initial surgery (P = 0.01) were associated with recurrence. Six of the 127 patients (0.5%) treated with hemi- or subtotal thyroidectomy experience recurrences, but no significant prognostic factor for recurrence was identified. Multivariate Cox-regression analysis showed that gender and cervical lymph node metastasis were significant variables
PTMC showed very diverse disease extent and could not be regarded as indolent, relatively benign disease based on the primary tumor size. The extent of surgery should be based on prognostic parameters, such as gender and lateral neck node metastasis, in patients with PTMC.
PMCID: PMC2576338  PMID: 18851763
12.  Is Routine Central Neck Dissection Necessary for the Treatment of Papillary Thyroid Microcarcinoma? 
It remains unclear as to whether routine central neck dissection (CND) is necessary when performing surgery to treat patients with papillary thyroid microcarcinoma (PTMC). To determine the necessity for routine CND in PTMC patients, we reviewed the clinicopathologic and laboratory data of the patients of PTMC.
Between September 2001 and July 2005, 101 patients with PTMC and clinical N0 disease were retrospectively reviewed. The study cohort was devided into groups: the total thyroidectomy plus CND group (the CND group, N=48) and the total thyroidectomy without CND group (the no CND group, N=53). The serum stimulated thyroglobulin (Tg) levels were measured after surgery and prior to radioactive iodine ablation therapy (RAI) and at 6-12 months after RAI. Pathology, the Tg levels and recurrence data were compared between the 2 groups.
Central nodal metastases were found in 18 of the 48 CND patients (37.5%). The incidence of Tg levels >5 ng/mL at RAI was higher in the no CND patients and in the 18 node-positive CND patients compared with the 30 node-negative CND patients (22-24% vs. 3%, respectively, P=0.020-0.058). The difference when performing a similar comparison using a >2 ng/mL Tg threshold level showed no significance (10-11% vs. 4%, respectively, P>0.1). Two of the no CND patients and one node-positive CND patient had recurrences in the thyroid bed or lateral neck during a mean follow-up of 24 months.
The data showed that occult metastasis to the central neck is common in PTMC patients. A CND provides pathologic information about the nodal metastases, and it potentially provides guidance for planning the postoperative RAI. However, the long-term benefit of CND on recurrence and survival remains somewhat questionable.
PMCID: PMC2671760  PMID: 19434261
Papillary microcarcinoma; Central compartment; Neck dissection; Neoplasm metastasis; Thyroglobulin
13.  Specific and common antigens of Clonorchis sinensis and Opisthorchis viverrini (Opisthorchidae, Trematoda) 
The antigenic characterizations and serological reactions of human liver flukes, Clonorchis sinensis and Opisthorchis viverrini, were analyzed by immunoblot. The antigenic profiles of the crude extract of Clonorchis contained major proteins of 8, 26-28, 34-37, 43, and 70 kDa, and those of Opisthorchis 34-37, 43, 70, and 100 kDa. Of these, the 8, 26-28 and 34-37 kDa bands of Clonorchis and the 100 kDa of Opisthorchis were major components of each excretory-secretory antigen. The 8 and 26-28 kDa bands were specific to Clonorchis but the 100 kDa of Opisthorchis cross-reacted with the sera of clonorchiasis, and the 34-37, 70 and 100 kDa bands cross-reacted with sera of other helminthiases. The frequency and intensity of the immunoblot reactions were positively correlated with the intensity of the liver fluke infection.
PMCID: PMC2717500  PMID: 12972729
Clonorchis sinensis; Opisthorchis viverrini; antigens; diagnosis

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