Colon cancer: the 2023 Korean clinical practice guidelines for diagnosis and treatment.

Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents.. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients' values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.

Clinical Feasibility of Deep Learning-Based Attenuation Correction Models for Tl-201 Myocardial Perfusion SPECT.

PURPOSE: We aimed to develop deep learning (DL)-based attenuation correction models for Tl-201 myocardial perfusion SPECT (MPS) images and evaluate their clinical feasibility. PATIENTS AND METHODS: We conducted a retrospective study of patients with suspected or known coronary artery disease. We proposed a DL-based image-to-image translation technique to transform non-attenuation-corrected images into CT-based attenuation-corrected (CT AC ) images. The model was trained using a modified U-Net with structural similarity index (SSIM) loss and mean squared error (MSE) loss and compared with other models. Segment-wise analysis using a polar map and visual assessment for the generated attenuation-corrected (GEN AC ) images were also performed to evaluate clinical feasibility. RESULTS: This study comprised 657 men and 328 women (age, 65 ± 11 years). Among the various models, the modified U-Net achieved the highest performance with an average mean absolute error of 0.003, an SSIM of 0.990, and a peak signal-to-noise ratio of 33.658. The performance of the model was not different between the stress and rest datasets. In the segment-wise analysis, the myocardial perfusion of the inferior wall was significantly higher in GEN AC images than in the non-attenuation-corrected images in both the rest and stress test sets ( P < 0.05). In the visual assessment of patients with diaphragmatic attenuation, scores of 4 (similar to CT AC images) or 5 (indistinguishable from CT AC images) were assigned to most GEN AC images (65/68). CONCLUSIONS: Our clinically feasible DL-based attenuation correction models can replace the CT-based method in Tl-201 MPS, and it would be useful in case SPECT/CT is unavailable for MPS.

Modulation of FDG Uptake by Cell Cycle Synchronization Using a T-Type Calcium Channel Inhibitor.

BACKGROUND: We investigated whether cell cycle synchronization induced by the T-type calcium channel inhibitor mibefradil could increase tumoral 2-[18F] fluoro-2-deoxy-d-glucose (FDG) uptake in vitro and in vivo. METHODS: Human prostate cancer cells (PC-3) were treated with 10 µM mibefradil for 24, 48, and 72 h to induce G1 arrest. Cell cycle distribution was analyzed at 0, 4, 8, 12, 15, 18, and 24 h after mibefradil withdrawal. Cellular uptake was measured after incubating cells with [3H] Deoxy-d-Glucose (DDG) for 1 h at the same time points used in the cell cycle analysis. The correlation between [3H] DDG uptake and each cell cycle phase was evaluated in the early (0-12 h) and late phases (15-24 h) of synchronization. In vivo FDG PET imaging was performed in PC-3-bearing mice at baseline, 24 h, and 48 h after mibefradil treatment. RESULTS: The G0/G1 fraction of PC-3 cells was significantly increased from 33.1% ± 0.2% to 60.9% ± 0.8% after 24 h mibefradil treatment, whereas the S and G2/M fractions were decreased from 36.3% ± 1.4% to 23.2% ± 1.1% and from 29.7% ± 1.3% to 14.9% ± 0.9%, respectively, which were similar to the results by serum starvation. Mibefradil treatment for 24, 48, and 72 h increased the number of cells in S phase at 18-24 h after withdrawal; however, only the 72 h treatment increased [3H] DDG uptake (145.8 ± 5.8% of control at 24 h after withdrawal). [3H] DDG uptake was positively correlated with the size of the S phase fraction and negatively correlated with the size of the G0/G1 fraction in the late phase of synchronization. DDG uptake was significantly increased by mibefradil-induced cell cycle synchronization and correlated with the sizes of cell cycle fractions. In vivo FDG PET imaging also demonstrated a significant increase in tumor uptake after mibefradil treatment. Quantified tumor FDG uptake (%ID/g) increased from 4.13 ± 2.10 to 4.7 ± 2.16 at 24 h, and 5.95 ± 2.57 at 48 h (p < 0.05). CONCLUSION: Cell cycle synchronization could be used to increase the diagnostic sensitivity of clinical FDG positron emission tomography.

Effect of withdrawal of thyroid hormones versus administration of recombinant human thyroid-stimulating hormone on renal function in thyroid cancer patients.

This study was conducted to investigate the effects of thyroid hormone withdrawal (THW) and recombinant human thyroid-stimulating hormone (rhTSH) administration on renal function in patients with thyroid cancer after total thyroidectomy. This study included 202 patients who discontinued thyroid hormone therapy and/or received rhTSH after total thyroidectomy. Creatinine (Cr), blood urea nitrogen (BUN) levels, and estimated glomerular filtration rate (eGFR) were assessed at the following three time points: before thyroidectomy, at least 3 weeks after THW, and 1 day after the second injection of rhTSH. The median serum Cr level was significantly higher following THW compared to that before thyroidectomy (0.95 versus 0.70). In contrast, the median BUN level was significantly lower after THW compared to that before thyroidectomy (9.8 versus 11.3). Over a fifth (22.2%) of patients had abnormal eGFR values after THW, which was significantly greater than that before thyroidectomy. In contrast, renal parameter values after rhTSH administration were not significantly different than those before thyroidectomy. In conclusion, THW affects renal function in patients with thyroid cancer who have undergone total thyroidectomy. However, renal function in such patients is not affected by rhTSH administration.

Sublingual Gland Observed on Salivary Gland Scan.

ABSTRACT: The major salivary glands, namely, the parotid, submandibular, and sublingual glands, are important in maintaining oral cavity health. A salivary gland scan is used to evaluate the uptake and excretory function of the salivary glands. By intravenously injecting 99m TcO 4- , which is distributed like chloride ions in the body, the glands become visible on the salivary gland scan. The parotid and submandibular glands are typically appreciated on the salivary gland scan, but the sublingual gland is not. We present a rare image of a prominent sublingual gland on a salivary gland scan.

F-18 FDG PET/CT in NK/T-Cell Lymphoma that Progressed from Epstein-Barr Virus-Associated Hemophagocytic Lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome involving an uncontrolled immune response with variable triggers. HLH is rare but highly fatal, even with proper treatment; therefore, early recognition and diagnosis are crucial for management. Although the role of F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in HLH is poorly defined, it can provide valuable information on disease status and possible triggers. Herein, we report an F-18 FDG PET/CT study on a case of NK/T-cell lymphoma that progressed from Epstein-Barr virus-associated HLH.

Incidence rate and factors associated with the development of secondary cancers after radioiodine therapy in differentiated thyroid cancer: a multicenter retrospective study.

PURPOSE: The objective of this study was to estimate the incidence of secondary cancers and the factors associated with their development among patients who underwent radioiodine therapy (RIT) with differentiated thyroid cancer. METHODS: We retrospectively collected medical records for patients who underwent first RIT between January 1, 2000, and December 31, 2005, from seven tertiary hospitals in South Korea after total thyroidectomy for differentiated thyroid cancer. Cancer incidence and calculated standardized rate ratio were compared with Korean cancer incidence data. The association between the development of secondary cancers and various parameters was analyzed by Cox-proportional hazard regression. RESULTS: A total of 3106 patients were included in this study. Mean age at the time of diagnosis of thyroid cancer was 45.7 ± 13.3 years old, and 2669 (85.9%) patients were female. The follow-up period was 11.9 ± 4.6 (range, 1.2-19.6) years. A total of 183 secondary cancers, which included 162 solid and 21 hematologic cancers, occurred in 173 patients (5.6%). There was no significant difference between solid cancer incidence in our study population who underwent RIT and the overall Korean population, but the incidence of hematologic cancers and total cancer in our study was significantly higher compared with that of the Korean population. A multivariate analysis identified independent prognostic factors for the development of secondary cancer including age at 1st RIT, male, and total cumulative dose over 200 mCi. CONCLUSION: We need to assess the risk benefit for patients who receive over 200 mCi of a total cumulative dose.

Simulating dose reduction for myocardial perfusion SPECT using a Poisson resampling method.

PURPOSE: The purpose of this study was to determine the lowest Tl-201 dose that does not reduce the image quality of myocardial perfusion SPECT (MPS) by Poisson resampling simulation. METHODS: One hundred and twelve consecutive MPS data from patients with suspected or known coronary artery disease were collected retrospectively. Stress and rest MPS data were resampled using the Poisson method with 33%, 50%, 67%, and 100% count settings. Two nuclear medicine physicians assessed the image quality of reconstructed data visually by giving grades from - 2 to + 2. The summed stress score (SSS), summed rest score (SRS), and summed difference score (SDS) were obtained on the workstation. Image quality grades and semi-quantitative scores were then compared among these resampled images. RESULTS: The proportions of "adequate" image quality were 0.48, 0.75, 0.92, and 0.96 for the groups of images with 33%, 50%, 67%, and 100% data, respectively. The quality of the resampled images was significantly degraded at 50% and 33% count settings, while the image quality was not different between 67 and 100% count settings. We also found that high body mass index further decreased image quality at 33% count setting. Among the semi-quantitative parameters, SSS and SRS showed a tendency to increase with a decline in count. CONCLUSION: Based on the simulation results, Tl-201 dose for MPS can be reduced to 74 MBq without significant loss of image quality. However, the SSS and SRS can be changed significantly, and it needs to be further verified under the different conditions.

Skeletal muscle mass at C3 may not be a strong predictor for skeletal muscle mass at L3 in sarcopenic patients with head and neck cancer.

PURPOSE: To evaluate the feasibility of using skeletal muscle mass (SMM) at C3 (C3 SMM) as a diagnostic marker for sarcopenia in head and neck cancer (HNC) patients. METHODS: We evaluated 165 HNC patients and 42 healthy adults who underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography scans. The paravertebral muscle area at C3 and skeletal muscle area at L3 were measured by CT. Pearson's correlation was used to assess the relationship between L3 and C3 SMMs. The prediction model for L3 SMM was developed by multiple linear regression. Then the correlation and the agreement between actual and predicted L3 SMMs were assessed. To evaluate the diagnostic value of C3 SMM for sarcopenia, the receiver operating characteristics (ROC) curves were analyzed. RESULTS: Of the 165 HNC patients, 61 (37.0%) were sarcopenic and 104 (63.0%) were non-sarcopenic. A very strong correlation was found between L3 SMM and C3 SMM in both healthy adults (r = 0.864) and non-sarcopenic patients (r = 0.876), while a fair association was found in sarcopenic patients (r = 0.381). Prediction model showed a very strong correlation between actual SMM and predicted L3 SMM in both non-sarcopenic patients and healthy adults (r > 0.9), whereas the relationship was moderate in sarcopenic patients (r = 0.7633). The agreement between two measurements was good for healthy subjects and non-sarcopenic patients, while it was poor for sarcopenic patients. On ROC analysis, predicted L3 SMM showed poor diagnostic accuracy for sarcopenia. CONCLUSIONS: A correlation between L3 and C3 SMMs was weak in sarcopenic patients. A prediction model also showed a poor diagnostic accuracy. Therefore, C3 SMM may not be a strong predictor for L3 SMM in sarcopenic patients with HNC.

Early-phase 18F-FP-CIT and 18F-flutemetamol PET were significantly correlated.

Little is known about whether early-phase PET images of 18F-FP-CIT match those of amyloid PET. Here, we compared early-phase 18F-FP-CIT and 18F-flutemetamol PET images in patients who underwent both within a 1-month interval. The SUVR on early-phase 18F-FP-CIT PET (median, 0.86) was significantly lower than that of 18F-flutemetamol PET (median, 0.91, p < 0.001) for total brain regions including all cerebral lobes and central structures. This significant difference persisted for each brain region except central structures (p = 0.232). The SUVR of total brain regions obtained from early 18F-FP-CIT PET showed a very strong correlation with that of 18F-flutemetamol PET (rho = 0.80, p < 0.001). Among the kinetic parameters, only R1 showed a statistically significant correlation between the two techniques for all brain regions (rho = 0.89, p < 0.001). R1 from 18F-FP-CIT (median, 0.77) was significantly lower in all areas of the brain compared to R1 from 18F-flutemetamol PET (median, 0.81, p < 0.001).18F-FP-CIT demonstrated lower uptake in cortical brain regions than 18F-flutemetamol on early-phase PET. However, both early-phase PETs demonstrated significant correlation of uptake.

Prognostic value of metabolic parameters measured by pretreatment dual-time-point 18F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with intrahepatic or perihilar cholangiocarcinoma: A STROBE study.

ABSTRACT: The purpose of this study was to determine the glucose metabolism at delay phase measured by pretreatment dual-time-point 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/ computed tomography (CT) provides prognostic information independent of well-known prognostic factors in patients with intrahepatic or perihilar cholangiocarcinoma (ICC or PCC).From July 2012 to December 2017, 55 patients (men 27, women 28, mean age 68 ±â€Š11 years) with pathologically proven ICC or PCC were enrolled in this retrospective study. The dual-time-point 18F-FDG PET/CT as part of a staging workup was performed in all patients. The patient's data includes age, sex, serum CA19-9, presence of LN or distant metastasis, early SUVmax (early maximum standardized uptake value [eSUV]), delay SUVmax (delay maximum standardized uptake value [dSUV]), retention index of SUVmax (percent change of maximum standardized uptake values [ΔSUV]), neutrophil to lymphocyte ratio (NLR) and histopathology including pCEA, p53, Ki-67 index. The analysis of the relationship between metabolic parameters and survival was done using the Kaplan-Meier curve and Cox proportional hazards regression model.Median survival for all patients was 357 days. Median early and delay SUVmax was 5.2 (range: 2.0-21.4) and 6.5 (range 2.7-24.5), respectively. The overall survival was found to be significantly related to eSUV, dSUV, ΔSUV, age, serum CA19-9 and NLR in univariate analysis. In multivariate analysis, dSUV (P = .014, 95%CI; 1.30-10.7, HR 3.74) and ΔSUVmax (P = .037, 95%CI; 1.05-6.12, HR 2.5) were independent factors of overall survival. Kaplan-Meier curve analysis clearly showed the significant difference of overall survival between 2 groups (high eSUV, low eSUV + high ΔSUV vs low eSUV and ΔSUV, P < .001) among the comparisons of the SUV parameters on FDG PET. In the receiver operating characteristic analysis using combinations of the SUV parameters, the 2 groups [eSUV + ΔSUV (P = .0001, area under the curve [AUC] 0.68) and dSUV + ΔSUV (P = .0002, AUC 0.71)] showed significantly larger AUC than the other groups applying eSUV or dSUV alone (AUC 0.61 and AUC 0.68).dSUV and ΔSUV on pretreatment dual-time-point 18F-FDG PET/CT can be useful parameters in the prediction of survival in patients with ICC or PCC.

Hilar Choledochal Cyst Mimicking Biliary Atresia on Hepatobiliary Scintigraphy: a Case Report.

Hepatobiliary scintigraphy has been widely used for the differential diagnosis of neonatal cholestasis. Relatively good hepatic uptake with no evidence of excretion into the bowel for up to 24 h is a representative finding of biliary atresia. Hepatobiliary scintigraphy has very high sensitivity and moderate specificity. Here, we report a false-positive case of hepatobiliary scintigraphy in a child with a choledochal cyst, which mimicked biliary atresia.

Comparison of bone single-photon emission computed tomography (SPECT)/CT and bone scintigraphy in assessing knee joints.

BACKGROUND: This study attempted to compare the radiopharmaceutical uptake findings of planar bone scintigraphy (BS) and single photon emission computed tomography (SPECT)/computed tomography (CT) performed on knee joints. METHODS: We retrospectively included 104 patients who underwent bone SPECT/CT and BS 4 h after the intravenous administration of technetium-99m-hydroxymethylene diphosphonate (99mTc-HDP) for pain in the knee joint. The uptake degree of each of the knee regions (medial femoral, lateral femoral, medial tibial, lateral tibial, and patellar area) in planar images and SPECT/CT were evaluated by visual (grades 0 to 2) and quantitative analyses (uptake counts for planar image and standardized uptake values [SUVs] for SPECT/CT). RESULTS: The uptake grades assessed visually on the planar images differed significantly from the uptake grades on SPECT/CT images in all areas of the knee (all p < 0.001), and SPECT/CT imaging revealed a larger number of uptake lesions than those noted in planar imaging for each patient (3.3 ± 2.0 vs 2.4 ± 2.3, p < 0.0001). In all regions of the knee, all of the quantitative values, including uptake counts obtained from the planar image as well as the maximum SUV (SUVmax) and mean SUV (SUVmean) obtained from SPECT/CT, showed statistically higher values as their visual grades increased (all p < 0.001). However, when analyzed for each area, only the SUVmax showed a significant difference by grade in all knee regions. Quantitative uptake values obtained from planar images were moderately correlated with SUVs of SPECT/CT images (r = 0.58 for SUVmean and r = 0.53 for SUVmax, all p < 0.001) in the total knee regions. Looking at each area, there was a significant but low correlation between the uptake counts of the planar images and the SUVs on SPECT/CT in the right lateral tibial region (r = 0.45 for SUVmean, r = 0.31 for SUVmax, all p < 0.001). CONCLUSIONS: In assessing knee joints, the findings of planar images and SPECT/CT images differ both visually and quantitatively, and more lesions can be found in SPECT/CT than in the planar images. The SUVmax could be a reliable value to evaluate knee joint uptake activity.

Recent Survey of Effective Doses of F-18 FDG Torso PET/CT in Korea and the Current Recommendations for CT Protocols of PET/CT.

PURPOSE: This study aimed to construct a database of the effective doses (ED) from F-18 fluorodeoxyglucose (FDG) torso positron emission tomography/computed tomography (PET/CT) in Korea to provide data that supports the reduction of the CT dose of PET/CT and optimization of PET/CT protocols in Korea. METHODS: We investigated data of ED and CT parameters of FDG PET/CT. The data were analyzed by body weight groups. RESULTS: A total of 31 hospitals participated in the survey (99 adults). The mean total EDs (± SD) were 8.77 ± 2.76, 10.93 ± 3.14, and 12.57 ± 3.79 mSv for the 55-, 70-, and 85-kg groups, respectively. The FDG EDs were 4.80 ± 0.98, 6.05 ± 1.15, and 6.89 ± 1.52 mSv, and the CT EDs were 4.00 ± 2.12, 4.88 ± 2.51, and 5.68 ± 2.89 mSv, respectively. Of the enrolled hospitals, 54.5% used ultra-low-dose CT protocols, and their CT ED was significantly lower than low-dose CT group in all groups (2.9 ± 1.0, 3.2 ± 1.1, and 3.3 ± 1.0 mSv vs. 6.6 ± 1.6, 7.2 ± 2.1, and 7.9 ± 2.2 mSv, all p < 0.001, respectively). In the ultra-low-dose CT group, the CT ED with the iterative reconstruction was significantly lower than that of CT without iterative reconstruction in the 55-kg group (2.4 ± 0.9 vs. 3.3 ± 0.9, p = 0.04). CONCLUSIONS: These results and current recommendations can be helpful for optimizing PET/CT diagnostic reference level (DRL) and reducing unnecessary PET/CT radiation exposure.

18F-fluorodeoxyglucose PET/CT as an independent predictor for patients with hepatocellular carcinoma combined with major portal vein tumor thrombus.

PURPOSE: Hepatocellular carcinoma (HCC) patients with major portal vein tumor thrombosis (mPVTT) complications were generally characterized by extremely poor prognoses. The aim of this study was to explore the role of 18F-fluorodeoxyglucose (18F-FDG) PET/CT imaging in predicting HCC complicated by mPVTT. METHODS: Five hundred one HCC patients received surgery in our hospital during November 2008 to December 2014, among which 32 patients (6.4%) were diagnosed as HCC complicated by mPVTT. Six cases were excluded for reasons of complex medical conditions, including 2 cases of salvage liver transplantation, 2 cases of re-resection, 1 case of mPVTT combined with inferior vina cava tumor thrombosis, and 1 case of residual portal vein tumor thrombosis. Ultimately, 26 cases were enrolled in this study. The maximal tumor standardized uptake value (SUVmax) was identified as a predictive factor and detected. The univariate and multivariate regression analyses were performed to identify the prognostic factors for recurrence-free survival (RFS) and overall survival (OS) of HCC patients complicated by mPVTT. RESULTS: Our results showed that the median OS was 16 months. The 1-, 3-, and 5-year cumulative OS was 55.6%, 31.7%, and 31.7%, respectively. The multivariate regression analysis revealed that SUVmax ≥ 4.65 was the only independent risk factor for RFS and OS. CONCLUSION: SUVmax was an independent predictor for RFS and OS of patients suffering from both HCC and mPVTT. L ow SUVmax could serve as an effective factor for selecting candidates with low recurrence risks and for helping with improving patient survival after surgical resection.

Current Perspectives on 89Zr-PET Imaging.

89Zr is an emerging radionuclide that plays an essential role in immuno-positron emission tomography (PET) imaging. The long half-life of 89Zr (t1/2 = 3.3 days) is favorable for evaluating the in vivo distribution of monoclonal antibodies. Thus, the use of 89Zr is promising for monitoring antibody-based cancer therapies. Immuno-PET combines the sensitivity of PET with the specificity of antibodies. A number of studies have been conducted to investigate the feasibility of 89Zr immuno-PET imaging for predicting the efficacy of radioimmunotherapy and antibody therapies, imaging target expression, detecting target-expressing tumors, and the monitoring of anti-cancer chemotherapies. In this review, we summarize the current status of PET imaging using 89Zr in both preclinical and clinical studies by highlighting the use of immuno-PET for the targets of high clinical relevance. We also present 89Zr-PET applications other than immuno-PET, such as nanoparticle imaging and cell tracking. Finally, we discuss the limitations and the ongoing research being performed to overcome the remaining hurdles.

Computed Tomography (CT) Protocols Associated with Cardiac and Bone Single-Photon Emission Computed Tomography/CT (SPECT/CT) in Korea.

PURPOSE: Single-photon emission computed tomography/computed tomography (SPECT/CT) is an advanced hybrid nuclear medicine technology that generates both functional and anatomical images in a single study. As utilization of SPECT/CT in Korea has been increasing, the purpose of this study was to survey its application of cardiac and skeletal SPECT/CT imaging for protocol optimization. METHODS: We surveyed CT protocols established for cardiac and skeletal SPECT/CT. We searched the guidelines for the CT protocols for SPECT/CT and reviewed the literature recently published. RESULTS: Among 36 hybrid SPECT scanners equipped with four or more multi-channel detector CTs (MDCTs), 18 scanners were used to perform cardiac studies at both very low current CT (30-80 mA; 11.1%) and ultra-low current CT (13-30 mA; 88.9%). Among the 33 canners, very low current (≤ 80 mA) CT or low current CT (80-130 mA) was used in 23.5%, and 41.8% for spine disorders, and in 36.4% or 30.3% for foot/ankle disorders, respectively. In the CT reconstructions, slice thickness of 5 mm for cardiac studies was most commonly used (94.4%); thinner slices (0.6-1.0 mm) for spine and foot/ankle studies were used in 24.2% and 45.5%, respectively. We also reviewed the international guidelines. CONCLUSIONS: The results and current recommendations will be helpful for optimizing CT protocols for SPECT/CT. Optimization of SPECT/CT protocols will be required for generating the proper strategy for the specific lesions and clinical purpose.

Therapeutic effect of mesenchymal stem cells in an animal model of Alzheimer's disease evaluated by ß-amyloid positron emission tomography imaging.

OBJECTIVE: We evaluated the effects of bone marrow-derived mesenchymal stem cells in a model of Alzheimer's disease using serial [18F]Florbetaben positron emission tomography. METHODS: 3xTg Alzheimer's disease mice were treated with intravenously injected bone marrow-derived mesenchymal stem cells, and animals without stem cell therapy were used as controls. Serial [18F]Florbetaben positron emission tomography was performed after therapy. The standardized uptake value ratio was measured as the cortex standardized uptake value divided by the cerebellum standardized uptake value. Memory function and histological changes were observed using the Barnes maze test and ß-amyloid-reactive cells. RESULTS: Standardized uptake value ratio decreased significantly from day 14 after stem cell administration in the bone marrow-derived mesenchymal stem cells-treated group (n = 28). In contrast, there was no change in the ratio in control mice (n = 25) at any time point. In addition, mice that received bone marrow-derived mesenchymal stem cell therapy also exhibited significantly better memory function and less ß-amyloid-immunopositive plaques compared to controls. CONCLUSION: The therapeutic effect of intravenously injected bone marrow-derived mesenchymal stem cells in a mouse model of Alzheimer's disease was confirmed by ß-amyloid positron emission tomography imaging, memory functional studies and histopathological evaluation.

Cell cycle synchronisation using thiazolidinediones affects cellular glucose metabolism and enhances the therapeutic effect of 2-deoxyglucose in colon cancer.

The effect of cell cycle synchronisation on glucose metabolism in cancer cells is not known. We assessed how cell cycle synchronisation by thiazolidinediones (TZDs) can affect glucose uptake by cancer cells and investigated the anti-cancer effect of combination therapy with TZDs and 2-deoxy-glucose (2-DG) in colon cancer cells and in mouse xenograft models. Troglitazone (58.1 ± 2.0 vs 48.6 ± 1.3%, p = 0.002) or pioglitazone (82.9 ± 1.9 vs 61.6 ± 3.4%, p < 0.001) induced cell cycle arrest in SW480 cells at G1 phase. Western blot analysis showed the degradation of cyclin D1 and CDK4, and an increase in the expression levels of p21 and p27 after TZDs treatment. Withdrawal of troglitazone treatment induced significant increase in cellular 3H-DG uptake (141.5% ± 12.9% of controls) and membrane GLUT1 expression levels (146.3% of controls) by 24 h; 1 mM 2-DG treatment alone decreased cell survival by 5.8% as compared with the controls.; however, combination therapy enhanced the anti-tumour effects to 34.6% or 20.3% as compared with control cells. In vivo, each combination treatment group showed significant anti-tumour effects unlike the 2-DG alone group. Cell cycle synchronisation using TZDs induced cellular glucose uptake, which significantly enhanced the therapeutic effect of 2-DG in colon cancer.

Clinicopathologic risk factors of radioactive iodine therapy based on response assessment in patients with differentiated thyroid cancer: a multicenter retrospective cohort study.

PURPOSE: We investigated whether predictive clinicopathologic factors can be affected by different response criteria and how the clinical usefulness of radioactive iodine (RAI) therapy should be evaluated considering variable factors in patients with differentiated thyroid carcinoma (DTC). METHODS: A total of 1563 patients with DTC who underwent first RAI therapy after total or near total thyroidectomy were retrospectively enrolled from 25 hospitals. Response to therapy was evaluated with two different protocols based on combination of biochemical and imaging studies: (1) serum thyroglobulin (Tg) and neck ultrasonography (US) and (2) serum Tg, neck US, and radioiodine scan. The responses to therapy were classified into excellent and non-excellent or acceptable and non-acceptable to minimize the effect of non-specific imaging findings. We investigated which factors were associated with response to therapy depending on the follow-up protocols as well as response classifications. Multivariate logistic regression analysis was performed to identify factors significantly predicting response to therapy. RESULTS: The proportion of patients in the excellent response group significantly decreased from 76.5 to 59.6% when radioiodine scan was added to the follow-up protocol (P < 0.001). Preparation method (recombinant human TSH vs. thyroid hormone withdrawal) was a significant factor for excellent response prediction evaluated with radioiodine scan (OR 2.129; 95% CI 1.687-2.685; P < 0.001) but was not for other types of response classifications. Administered RAI activity, which was classified as low (1.11 GBq) or high (3.7 GBq or higher), significantly predicted both excellent and acceptable responses regardless of the follow-up protocol. CONCLUSIONS: The clinical impact of factors related to response prediction differed depending on the follow-up protocol or classification of response criteria. A high administered activity of RAI was a significant factor predicting a favorable response to therapy regardless of the follow-up protocol or classification of response criteria.