Temporal Changes in 18 F-FDG PET/CT in Familial Neuronal Intranuclear Inclusion Disease, Based on the Clinical Course.

ABSTRACT: We report temporal changes in 18 F-FDG PET/CT in neuronal intranuclear inclusion disease (NIID). In a patient with encephalitis-like episodes, PET showed hypermetabolism correlating with EEG alterations. Affected sites later became hypometabolic and showed diffusion changes on MRI. In another patient, hypermetabolic regions correlated well with the EEG, whereas MRI showed changes after only 1 month. One chronic patient had diffuse hypometabolism, which correlated with atrophy on MRI and cerebral dysfunction on EEG. This is the first report of temporal changes in PET in NIID and suggests that it reflects the disease activity of NIID while correlating well with EEG.

Generation of Conventional 18F-FDG PET Images from 18F-Florbetaben PET Images Using Generative Adversarial Network: A Preliminary Study Using ADNI Dataset.

Background and Objectives: 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) (PETFDG) image can visualize neuronal injury of the brain in Alzheimer's disease. Early-phase amyloid PET image is reported to be similar to PETFDG image. This study aimed to generate PETFDG images from 18F-florbetaben PET (PETFBB) images using a generative adversarial network (GAN) and compare the generated PETFDG (PETGE-FDG) with real PETFDG (PETRE-FDG) images using the structural similarity index measure (SSIM) and the peak signal-to-noise ratio (PSNR). Materials and Methods: Using the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, 110 participants with both PETFDG and PETFBB images at baseline were included. The paired PETFDG and PETFBB images included six and four subset images, respectively. Each subset image had a 5 min acquisition time. These subsets were randomly sampled and divided into 249 paired PETFDG and PETFBB subset images for the training datasets and 95 paired subset images for the validation datasets during the deep-learning process. The deep learning model used in this study is composed of a GAN with a U-Net. The differences in the SSIM and PSNR values between the PETGE-FDG and PETRE-FDG images in the cycleGAN and pix2pix models were evaluated using the independent Student's t-test. Statistical significance was set at p ≤ 0.05. Results: The participant demographics (age, sex, or diagnosis) showed no statistically significant differences between the training (82 participants) and validation (28 participants) groups. The mean SSIM between the PETGE-FDG and PETRE-FDG images was 0.768 ± 0.135 for the cycleGAN model and 0.745 ± 0.143 for the pix2pix model. The mean PSNR was 32.4 ± 9.5 and 30.7 ± 8.0. The PETGE-FDG images of the cycleGAN model showed statistically higher mean SSIM than those of the pix2pix model (p < 0.001). The mean PSNR was also higher in the PETGE-FDG images of the cycleGAN model than those of pix2pix model (p < 0.001). Conclusions: We generated PETFDG images from PETFBB images using deep learning. The cycleGAN model generated PETGE-FDG images with a higher SSIM and PSNR values than the pix2pix model. Image-to-image translation using deep learning may be useful for generating PETFDG images. These may provide additional information for the management of Alzheimer's disease without extra image acquisition and the consequent increase in radiation exposure, inconvenience, or expenses.

Di-indenopyridines as topoisomerase II-selective anticancer agents: Design, synthesis, and structure-activity relationships.

Topoisomerases are key molecular enzymes responsible for altering DNA topology, thus they have long been considered as attractive targets for novel chemotherapeutic agents. Topoisomerase type II (Topo II) catalytic inhibitors embrace a fresh perspective meant to get beyond drawbacks caused by topo II poisons, such as cardiotoxicity and secondary malignancies. Based on previously reported 5H-indeno[1,2-b]pyridines, here we presented new twenty-three hybrid di-indenopyridines along with their topo I/IIα inhibitory and antiproliferative activity. Most of the prepared 11-phenyl-diindenopyridines showed negligible topo I inhibitory activity, showing selectivity over topo II. Among the series, we finally selected compound 17, which displayed 100 % topo IIα inhibition at 20 µM concentration and comparable antiproliferative activity against the tested cell lines. Through competitive EtBr displacement assay, cleavable complex assay, and comet assay, compound 17 was finally determined as a non-intercalative catalytic topo IIα inhibitor. The findings in this study highlight the significance of phenolic, halophenyl, thienyl, and furyl groups at the 4-position of the indane ring in the design and synthesis of di-indenopyridines as potent catalytic topo IIα inhibitors with remarkable anticancer effects.

A Case of Adenomyosis Showing Size Reduction in a Follicular Lymphoma Patient Receiving Chemotherapy With R-Bendamustine.

ABSTRACT: We describe a case of adenomyosis that reduced in size in a patient with lymphoma on receiving chemotherapy. A 48-year-old woman with worsening left flank pain was diagnosed with follicular lymphoma. [ 18 F]FDG PET/CT revealed multiple hypermetabolic lymph nodes in the bilateral cervical, axillary, mediastinal, mesenteric, retroperitoneal, iliac, and inguinal regions. In addition, adenomyosis with mild hypermetabolism was demonstrated on [ 18 F]FDG PET/CT. The size and metabolism of adenomyosis decreased after chemotherapy with R-bendamustine; in addition, along with decrease in estradiol levels, the patient experienced amenorrhea and hot flushes. The patient was diagnosed with chemotherapy-induced early menopause.

The Use of F-18 FDG PET-Based Cognitive Reserve to Evaluate Cognitive Decline in Alzheimer's Disease, Independent of Educational Influence.

Background and Objectives: The optimal assessment of cognitive function, including the impact of education, is crucial in managing Alzheimer's disease (AD). This study aimed to evaluate the role of cognitive reserve (CR), represented by the metabolic status of regions of the cerebral cortex, to evaluate cognitive decline considering the educational attainment of patients with AD. Materials and Methods: We used data from the Alzheimer's Disease Neuroimaging Initiative database, and selected 124 patients who underwent both baseline F-18 fluorodeoxyglucose (FDG) and F-18 florbetaben (FBB) positron emission tomography (PET) scans. Demographics, cognitive function variables (Clinical Dementia Rating-Sum of Boxes [CDR]; AD Assessment Scale 11/13 [ADAS11/13] Mini-Mental State Examination [MMSE]), and the average standardized uptake value ratio (SUVR) of cerebral cortex regions to those of the cerebellum were obtained from the data. The participants' education level was divided into low and high education subgroups using four cut-offs of 12, 14, 16, and 18 years of educational attainment (G12, G14, G16, and G18, respectively). Demographic and cognitive function variables were compared between the two subgroups in each of the four groups, and their correlations with the SUVRs were evaluated. Results: There was no significant difference between the high and low education subgroups in each of the four groups, except for ADAS11/13 and MMSE in G14 and age in G16. The SUVRs of FDG PET (FDGSUVR) were significantly correlated with CDR, ADAS11/13, and MMSE scores. FDGSUVR showed different trajectories of neurodegeneration between the low and high education groups. Conclusions: FDGSUVR correlated moderately but significantly with neuropsychological test results, without being influenced by education level. Therefore, FDG PET may reflect CR independent of education level, and therefore could be a reliable tool to evaluate cognitive decline in AD.

Assessment of Instability in Thoracolumbar Burst Fractures Using a New Bone Scan Scoring System.

Background and Objectives: Unstable thoracolumbar burst fractures require surgical management as they can result in neurological deficits if left untreated. This study aimed to evaluate whether a new bone scan scoring system could accurately assess instability in thoracolumbar burst fractures. Materials and Methods: Fifty-two patients with thoracolumbar burst fractures who underwent bone scans and magnetic resonance imaging prior to surgery between January 2015 and August 2017 at Ulsan University Hospital were selected for inclusion. Instability was determined by clinical assessment and imaging, and the Thoracolumbar Injury Classification and Severity score was determined. Bone scans were visually evaluated using a new bone scan scoring system. Bone scan findings of vertebral body (BB) and posterior column (BP) were scored separately and were summed to produce BTS {BTS (total score) = BB (body score, 5 points) + BP (posterior score, 2 points)}. The diagnostic performance of the scoring system for identifying unstable then thoracolumbar burst fractures were assessed. Results: Of the 52 thoracolumbar burst fractures, 34 (65.4%) were unstable and 31 (59.6%) had a Thoracolumbar Injury Classification and Severity score ≥ 5. The diagnostic performance of using BTS ≥ 4 to identify unstable thoracolumbar burst fractures and those with a Thoracolumbar Injury Classification and Severity score ≥ 5 was as follows: sensitivity, 61.8% and 58.1%; specificity, 94.4% and 81.0%; positive predictive value, 95.5% and 81.8%; and negative predictive value, 56.7% and 56.7%, respectively. Conclusions: The proposed bone scan scoring system has a high specificity and positive predictive value for identifying thoracolumbar burst fractures that are unstable or have a Thoracolumbar Injury Classification and Severity score ≥ 5. This scoring system may help to inform decisions regarding surgical management.

Comparison of the gut microbiome of sacbrood virus-resistant and -susceptible Apis cerana from South Korea.

Honey bees are important pollinators for the conservation of the ecosystem and agricultural products and provide a variety of products important for human use, such as honey, pollen, and royal jelly. Sacbrood disease (SD) is a devastating viral disease in Apis cerana; an effective preventive measure for SD is urgently needed. In this study, the relationship between the gut microbiome of honey bees and SD was investigated by pyrosequencing. Results revealed that sacbrood virus (SBV)-resistant A. cerana strains harbour a unique acetic acid bacterium, Bombella intestini, and the lactic acid bacteria (LAB) Lactobacillus (unclassified)_uc, Bifidobacterium longum, B. catenulatum, Lactococcus lactis, and Leuconostoc mesenteroides in larvae and Hafnia alvei, B. indicum, and the LAB L. mellifer and Lactobacillus HM215046_s in adult bees. Changes in the gut microbiome due to SBV infection resulted in loss of bacteria that could affect host nutrients and inhibit honey bee pathogens, such as Gilliamella JFON_s, Gilliamella_uc, Pseudomonas putida, and L. kunkeei in A. cerana larvae and Frischella_uc, Pantoea agglomerans, Snodgrassella_uc, and B. asteroides in adult bees. These findings provide important information for the selection of probiotics for A. cerana larvae and adults to prevent pathogenic infections and keep honey bees healthy.

Feasibility of robotic thyroidectomy via hairline incision using da Vinci single port system: Initial experience with 40 consecutive cases.

BACKGROUND: This study aimed to introduce our robotic technique, which can minimize dissection extent using the da Vinci SP robotic system via hairline incision. METHODS: Forty patients underwent robotic thyroidectomy using the da Vinci SP robotic system via a hairline incision between February 2020 and April 2021 at Ulsan University Hospital. All procedures were performed successfully by one surgeon using the SP robotic system. RESULTS: Hemithyroidectomies were performed in 32 patients and total thyroidectomies in eight patients. Central neck dissection was performed in 32 patients. The overall mean operative time was 140.2 ± 50.7 min, and the mean console time was 74.0 ± 42.7 min. All patients were discharged on the second or third day after operation without any complications. CONCLUSIONS: Robotic thyroidectomy using the SP robotic system via hairline incision is technically feasible and safe, with a shorter incision length when compared with that of the Xi system.

Clinicopathologic Characteristics Associated with Prognosis in Ocular Extranodal Marginal Zone B Cell Lymphoma.

Background and Objectives: Extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT) type is the most common subtype of the ocular adnexal lymphoma. Despite its excellent prognosis, some patients experience partial remission or progressive disease. We aimed to evaluate clinicopathologic differences in the treatment responder group by comparing complete remission (CR) and non-complete remission (non-CR). Materials and Methods: This study retrospectively reviewed 48 patients who were diagnosed with ocular adnexal MALT lymphoma at Ulsan University Hospital between March 2002 and August 2018. Patients who were followed up for less than 6 months were excluded. Histologic and clinical features were analyzed. The patients were divided into two groups: CR and non-CR. Results: Among the 48 patients, 33 achieved CR and 15 achieved non-CR during the median follow-up period of 40.00 months (range, 7-109 months). In univariable analysis, more patients tend to undergo treatment in the CR group, and post-radiotherapy (post-RT) SUVmax, PET and serum lactate dehydrogenase (LDH) levels were higher in the non-CR group (p = 0.043, p = 0.016, and p = 0.042, respectively). In a multivariable analysis, only application of treatment, including radiotherapy or chemotherapy with immunotherapy, was related to CR (odd ratio 7.301, 95% confidence interval 1.273-41.862, p = 0.026). In subgroup analysis according to the site of involvement, none of the variables were significant except for the post-RT SUVmax of PET and level of serum LDH in the non-conjunctiva group (p = 0.026, and p = 0.037, respectively). Seven (14.6%) patients had a recurrence, and those with a recurring site other than the primary site had a higher Ki-67 labeling index, although it was not statistically significant (9.56% vs. 18.00%, p = 0.095). Conclusions: Although belonging to the early stages, the non-CR rate was high in patients with high serum LDH levels, and recurred patients had higher Ki-67. Thus, considering active treatment is recommended in this group of patients.

Smad4 and p53 synergize in suppressing autochthonous intestinal cancer.

BACKGROUND: Smad4 and p53 mutations are the most common mutations in human colorectal cancers (CRCs). We evaluated whether and how they are synergistic in intestinal carcinogenesis using novel autochthonous mouse models. METHOD: To recapitulate human CRCs, we generated Villin-Cre;Smad4F / F ;Trp53F / F mice. We then compared the intestinal phenotype of Villin-Cre;Smad4F / F ;Trp53F / F mice (n = 40) with Villin-Cre;Smad4F / F (n = 30) and Villin-Cre;Trp53F / F mice (n = 45). RESULTS: Twenty-week-old Villin-Cre;Smad4F / F ;Trp53F / F mice displayed spontaneous highly proliferative intestinal tumors, and 85% of mice developed adenocarcinomas. p21 was downregulated in the intestinal mucosa in Villin-Cre;Smad4F / F ;Trp53F / F mice than in Villin-Cre;Smad4F / F and Villin-Cre;Trp53F / F mice. Villin-Cre;Smad4F / F ;Trp53F / F mice displayed multistep intestinal tumorigenesis and Wnt activation. Long-term CWP232291 (small-molecule Wnt inhibitor) treatment of Villin-Cre;Smad4F / F ;Trp53F / F mice suppressed intestinal tumorigenesis and progression. CWP232291 treatment downregulated cancer stem cell (CSC) tumor markers including CD133, Lgr-5, and Sca-1. CWP232291 treatment reduced the CSC frequency. Small-molecule Wnt inhibitors reduced intestinal CSC populations and inhibited their growth, along with Bcl-XL downregulation. Furthermore, BH3I-1, a Bcl-XL antagonist, increasingly inhibited intestinal CSCs than bulk tumor cells. CONCLUSION: Smad4 loss and p53 loss are synergistic in autochthonous intestinal carcinogenesis, by downregulating p21 and activating Wnt/ß-catenin pathway.

Amyloid Arthropathy and Pseudomyopathy Associated With Multiple Myeloma Detected by 18F-Florapronol Amyloid PET/CT.

ABSTRACT: We report a case of amyloid arthropathy and pseudomyopathy with multiple myeloma, detected by amyloid PET/CT using 18F-florapronol. Bone scintigraphy and 18F-FDG PET/CT in a multiple myeloma patient revealed uneven soft tissue uptakes, especially at periarticular areas. The joint capsule and intermuscular fascia showed enhancement on CT, whereas muscle enzymes were normal. These suggested amyloid arthropathy with pseudomyopathy. 18F-Florapronol amyloid PET/CT showed extensive soft tissue uptakes. Amyloid arthropathy and pseudomyopathy were confirmed after biopsy. This is the first report of amyloid PET/CT aiding in the diagnosis of unusual presentation of systemic amyloidosis.

PET Imaging of System xC - in Immune Cells for Assessment of Disease Activity in Mice and Patients with Inflammatory Bowel Disease.

We aimed to explore whether the imaging of antiporter system xC - of immune cells with (4S)-4-(3-18F-fluoropropyl)-l-glutamate (18F-FSPG) PET can assess inflammatory bowel disease (IBD) activity in murine models and patients (NCT03546868). Methods: 18F-FSPG PET imaging was performed to assess IBD activity in mice with dextran sulfate sodium-induced and adoptive T-cell transfer-induced IBD and a cohort of 20 patients at a tertiary care center in South Korea. Immunohistochemical analysis of system xC - and cell surface markers was also studied. Results: Mice with experimental IBD showed increased intestinal 18F-FSPG uptake and xCT expression in cells positive (+) for CD11c, F4/80, and CD3 in the lamina propria, increases positively associated with clinical and pathologic disease activity. 18F-FSPG PET studies in patients, most of whom were clinically in remission or had mildly active IBD, showed that PET imaging was sufficiently accurate in diagnosing endoscopically active IBD and remission in patients and bowel segments. 18F-FSPG PET correctly identified all 9 patients with superficial or deep ulcers. Quantitative intestinal 18F-FSPG uptake was strongly associated with endoscopic indices of IBD activity. The number of CD68+xCT+ and CD3+xCT+ cells in 22 bowel segments from patients with ulcerative colitis and the number of CD68+xCT+ cells in 7 bowel segments from patients with Crohn disease showed a significant positive association with endoscopic indices of IBD activity. Conclusion: The assessment of system xC - in immune cells may provide diagnostic information on the immune responses responsible for chronic active inflammation in IBD. 18F-FSPG PET imaging of system xC - activity may noninvasively assess the IBD activity.

Identification of new halogen-containing 2,4-diphenyl indenopyridin-5-one derivative as a boosting agent for the anticancer responses of clinically available topoisomerase inhibitors.

Based on previous reports on the significance of halogen moieties and the indenopyridin-5-one skeleton, we designed and synthesized a novel series of halogen (F-, Cl-, Br-, CF3- and OCF3-)-containing 2,4-diphenyl indenopyridin-5-ones and their corresponding -5-ols. Unlike indenopyridin-5-ols, most of the prepared indenopyridin-5-ones with Cl-, Br-, and CF3- groups at the 2-phenyl ring conferred a strong dual topoisomerase I/IIα inhibitory effect. Among the series, para-bromophenyl substituted compound 9 exhibited the most potent topoisomerase inhibition and antiproliferative effects, which showed dependency upon the topoisomerase gene expression level of diverse cancer cells. In particular, as a DNA minor groove-binding non-intercalative topoisomerase I/IIα catalytic inhibitor, compound 9 synergistically promoted the anticancer efficacy of clinically applied topoisomerase I/IIα poisons both in vitro and in vivo, having the great advantage of alleviating poison-related toxicities.

Acute Abdominal Pain due to Accessory Splenic Infarction in an Adult: A Case Report.

Accessory spleens are common congenital anatomic variations that are usually asymptomatic. On the other hand, they can be clinically significant if complicated by hemorrhage, torsion, or infarction. This paper describes a case of an infarcted accessory spleen in a 30-year-old male who presented with abdominal pain. Abdominal CT and MRI revealed an isolated mass, 4.5 cm in size, in the perisplenic area. An infarcted accessory spleen was suspected. The patient underwent laparoscopic accessory splenectomy. Histopathology identified the mass as splenic tissue that had undergone ischemic necrosis. A definitive diagnosis of an infarcted accessory spleen was made, and the patient was discharged on day 5 after surgery symptom-free.

4-Flourophenyl-substituted 5H-indeno[1,2-b]pyridinols with enhanced topoisomerase IIα inhibitory activity: Synthesis, biological evaluation, and structure-activity relationships.

A series of fluorinated and hydroxylated 2,4-diphenyl indenopyridinols were designed and synthesized using l-proline-catalyzed and microwave-assisted synthetic methods for the development of new anticancer agents. Adriamycin and etoposide were used as reference compounds for the evaluation of topo IIα inhibitory and anti-proliferative activity of the synthesized compounds. Exploring the structure-activity relationships of 36 prepared compounds and biological results, most of the compounds with ortho- and para-fluorophenyl at 4-position of indenopyridinol ring displayed strong topo IIα inhibition. In addition, the majority of the ortho- and meta-fluorophenyl substituted compounds 1-24 displayed strong anti-proliferative activity against DU145 prostate cancer cell line compared to the positive controls. Interestingly, compound 4 possessing ortho-phenolic and ortho-fluorophenyl group at 2- and 4-position, respectively of the central pyridine ring showed high anti-proliferative activity (IC50 = 0.82 µM) against T47D human breast cancer cell line, while para-phenolic and para-fluorophenyl substituted compound 36 exhibited potent topo IIα inhibitory activity with 94.7% and 88.6% inhibition at 100 µM and 20 µM concentration, respectively. A systematic comparison between the results of this study and the previous study indicated that minor changes in the position of functional groups in the structure affect the topo IIα inhibitory activity and anti-proliferative activity of the compounds. The findings from this study will provide valuable information to the researchers working on the medicinal chemistry of topoisomerase IIα-targeted anticancer agents.

A 4-Year Follow-Up of Subjects with Visually Equivocal Amyloid Positron Emission Tomography Findings from the Alzheimer's Disease Neuroimaging Initiative Cohort.

BACKGROUND: To date, the clinical significance of visually equivocal amyloid positron emission tomography (PET) has not been well established. OBJECTIVE: We studied the clinical significance of equivocal amyloid PET images from the Alzheimer's Disease Neuroimaging Initiative (ADNI). METHODS: Subjects with F-18 florbetapir PET scans at baseline who were followed up for 4 years were selected. Clinical characteristics, imaging biomarkers, cognitive function, and rate of conversion to AD were compared in subjects with visually equivocal findings. RESULTS: Of 249 subjects who completed the follow-up, 153 (61.4%), 20 (8.0%), and 129 (30.5%) were F-18 florbetapir-negative, -equivocal, and -positive, respectively. The mean standardized uptake value ratios (SUVR) of F-18 florbetapir PET were 0.75 ± 0.04, 0.85 ± 0.10, and 1.00 ± 0.09 for each group (p <0.001 between groups), and 15.0%, 70.0%, and 98.7% of patients were quantitatively above the positive threshold. The change in the SUVR of F-18 florbetapir PET was higher in the equivocal (6.09 ± 3.61%, p <0.001) and positive (3.13 ± 4.38%, p <0.001) groups than the negative group (0.88 ± 4.28%). Among the subjects with normal or subjective memory impairment and mild cognitive impairment, 5.3% with negative amyloid PET and 37.5% with positive amyloid PET converted to AD over the 4-year period. None of the equivocal amyloid PET subjects converted to AD during this period. CONCLUSION: Approximately 8% of subjects from the ADNI cohort showed visually equivocal amyloid PET scans with intermediate load and rapid accumulation of amyloid, but did not convert to AD during the 4-year follow-up.

Anticancer Activity of Indeno[1,2-b]-Pyridinol Derivative as a New DNA Minor Groove Binding Catalytic Inhibitor of Topoisomerase IIα.

Topoisomerase IIα has been a representative anti-cancer target for decades thanks to its functional necessity in highly proliferative cancer cells. As type of topoisomerase IIα targeting drugs, topoisomerase II poisons are frequently in clinical usage. However, topoisomerase II poisons result in crucial consequences resulted from mechanistically induced DNA toxicity. For this reason, it is needed to develop catalytic inhibitors of topoisomerase IIα through the alternative mechanism of enzymatic regulation. As a catalytic inhibitor of topoisomerase IIα, AK-I-191 was previously reported for its enzyme inhibitory activity. In this study, we clarified the mechanism of AK-I-191 and conducted various types of spectroscopic and biological evaluations for deeper understanding of its mechanism of action. Conclusively, AK-I-191 represented potent topoisomerase IIα inhibitory activity through binding to minor groove of DNA double helix and showed synergistic effects with tamoxifen in antiproliferative activity.

Should Total Thyroidectomy Be Recommended for Patients with Familial Non-medullary Thyroid Cancer?

BACKGROUND: It is unknown whether familial non-medullary thyroid cancer (FNMTC) has more aggressive clinical features and a worse prognosis than sporadic non-medullary thyroid cancer (SNMTC). METHODS: We retrospectively reviewed 2894 patients with differentiated thyroid cancer who underwent primary thyroidectomy, identified 391 FNMTC cases, and compared the prevalence, surgical extension, and clinicopathologic features of FNMTC and SNMTC. RESULTS: A family history of thyroid cancer was noted in 391 patients (13.5%), with 85% having two affected relatives and 15% with ≥3 affected relatives. A sibling was affected in 52.9% of cases, and in 47.1%, both parent and child were affected. There were no significant between-group differences in sex, age, tumor size, extrathyroidal extension, or central lymph node metastases. Significantly more patients with FNMTC exhibited multifocal disease (p = 0.020) or benign nodules (p = 0.015). Lateral neck lymph node metastases were noted in 6.6% (SNMTC) and 9.7% (FNMTC, p = 0.021) of patients. Multifocality and combined benign masses were more frequently observed in patients with FNMTC in multivariate analysis. In the FNMTC group, seven experienced disease recurrence, with no mortality noted during follow-up. CONCLUSIONS: FNMTC is not more aggressive than SNMTC; however, FNMTC should be treated with total thyroidectomy because of the increased disease multifocality and the presence of benign nodules. Lateral neck lymph node metastases were more likely in patients with FNMTC, although we could not estimate prognosis. All patients with thyroid cancer should be checked for family disease history and undergo preoperative ultrasonography to determine the extent of node dissection and the need for total thyroidectomy.

Clinicopathological characteristics of primary central nervous system lymphoma with low 18F-fludeoxyglucose uptake on brain positron emission tomography.

Primary central nervous system lymphoma (PCNSL) typically shows a strong uptake of F-fludeoxyglucose (FDG) imaged by positron emission tomography (PET). Uncommonly, PCNSL demonstrates a low uptake on FDG PET. We investigated the clinicopathological characteristics of the unusual cases of PCNSL with low FDG uptake.We retrospectively enrolled 104 consecutive patients with newly diagnosed PCNSL who underwent baseline brain FDG PET. The degree of FDG uptake of PCNSL was visually scored by 4 grades (0, ≤contralateral white matter; 1, >contralateral white matter and contralateral gray matter). Grades 0-2 were considered as PCNSL with low uptake. We investigated association of low uptake of PCNSL with the following clinicopathological factors: age, sex, steroid treatment, lactate dehydrogenase level, cerebrospinal fluid protein level, condition of PET scanning, immunohistochemical markers (cluster of differentiation 10 [CD10], B-cell lymphoma 6 [BCL-6], B-cell lymphoma 2 [BCL-2], multiple myeloma oncogene 1 [MUM1], Epstein-Barr virus [EBV] protein, and Ki67), location of lesions, tumor size, multiplicity of lesions, involvement of deep brain structures, and cystic or necrotic appearance of lesions.Of the 104 patients with PCNSL, 14 patients (13.5%) showed PCNSL with low FDG uptake on PET. Among various clinicopathological factors, MUM1 negativity was the only factor associated with low FDG uptake PCNSL by univariate (P = .002) and multivariate analysis (P = .007).This study suggests that the different clinicopathological characteristics between patients with high uptake and low uptake of PCNSL on FDG PET is closely associated with lack of MUM1, a protein known to be a crucial regulator of B-cell development and tumorigenesis.

Small Animal PET Imaging of hTERT RNA-Targeted HSV1-tk Gene Expression with Trans-Splicing Ribozyme.

Background: Trans-splicing ribozymes (TSR) are useful anticancer agents targeting cancer-specific transcripts and replacing the RNA to induce anticancer gene expression specifically and selectively in cancer cells. Similar to other gene therapy methods, it is also important to evaluate the transgene expression for target specificity and ribozyme activity. Materials and Methods: In this study, the authors performed in vivo small animal positron emission tomography (PET) imaging and biodistribution assay to evaluate human telomerase reverse transcriptase (hTERT) RNA-targeting-specific TSR, which directs the expression of herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene selectively in hTERT-positive tumors through targeted RNA replacement of the hTERT transcript. Results: The hTERT RNA-targeted HSV1-tk expression with TSR was monitored by PET imaging with 124I labeled 2'-fluoro-2'-deoxy-1-ß-D-arabinofuranosyl-5-iodouracil, which is one of the thymidine derivatives acting as substrates for HSV1-tk, in hTERT-positive tumor-bearing mice. Conclusions: Imaging of hTERT RNA-targeted HSV1-tk expression by TSR could be used in the development of advanced gene therapy using tumor-specific TSR.