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Hereditary spastic paraplegia (HSP) is a heterogeneous group of neurological disorders that are characterized by progressive spasticity and weakness in the lower limbs. SPG26 is a complicated form of HSP, which includes not only weakness in the lower limbs, but also cognitive impairment, developmental delay, cerebellar ataxia, dysarthria, and peripheral neuropathy, and is caused by biallelic mutations in the B4GALNT1 (beta-1,4- N -acetylgalactosaminyltransferase 1) gene. The B4GALNT1 gene encodes ganglioside GM2/GD2 synthase (GM2S), which catalyzes the transfer of N -acetylgalactosamine to lactosylceramide, GM3, and GD3 to generate GA2, GM2, and GD2, respectively. The present study attempted to characterize a novel B4GALNT1 variant (NM_001478.5:c.937G>A p.Asp313Asn) detected in a patient with progressive multi-system neurodegeneration as well as deleterious variants found in the general population in Japan. Peripheral blood T cells from our patient lacked the ability for activation-induced ganglioside expression assessed by cell surface cholera toxin binding. Structural predictions suggested that the amino acid substitution, p.Asp313Asn, impaired binding to the donor substrate UDP-GalNAc. An in vitro enzyme assay demonstrated that the variant protein did not exhibit GM2S activity, leading to the diagnosis of HSP26. This is the first case diagnosed with SPG26 in Japan. We then extracted 10 novel missense variants of B4GALNT1 from the whole-genome reference panel jMorp (8.3KJPN) of the Tohoku medical megabank organization, which were predicted to be deleterious by Polyphen-2 and SIFT programs. We performed a functional evaluation of these variants and demonstrated that many showed perturbed subcellular localization. Five of these variants exhibited no or significantly decreased GM2S activity with less than 10% activity of the wild-type protein, indicating that they are carrier variants for HSP26. These results provide the basis for molecular analyses of B4GALNT1 variants present in the Japanese population and will help improve the molecular diagnosis of patients suspected of having HSP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Inamori, Nakamura, Shishido, Hsu, Nagafuku, Nitta, Ikeda, Yoshimura, Kodaira, Tsuchida, Matsumoto, Uemura, Ohno, Manabe, Yamaguchi, Togayachi, Aoki-Kinoshita, Nishihara, Furukawa, Kaname, Nakamura, Shimohata, Tadaka, Shirota, Kinoshita, Nakamura, Ohno, Sekijima and Inokuchi.)

Background: ST3GAL5 encodes GM3 synthase (ST3 beta-galactoside alpha-2,3-sialyltransferase 5; ST3GAL5), which synthesizes GM3 by transferring sialic acid to lactosylceramide. GM3, a sialic acid-containing glycosphingolipid known as ganglioside, is a precursor to the biosynthesis of various more complex gangliosides that are active in the brain. Biallelic variants in ST3GAL5 cause GM3 synthase deficiency (GM3SD), a rare congenital disorder of glycosylation. GM3SD was first identified in the Amish population in 2004., Case: We report two siblings diagnosed with GM3SD due to novel compound heterozygous ST3GAL5 variants. The novel ST3GAL5 variants, detected by whole-exome sequencing in the patients, were confirmed to be pathogenic by GM3 synthase assay. The clinical courses of these patients, which began in infancy with irritability and growth failure, followed by developmental delay and hearing loss, were consistent with previous case reports of GM3SD. The older sibling underwent deep brain stimulation for severe involuntary movements at the age of 9 years. The younger sibling suffered from acute encephalopathy at the age of 9 months and subsequently developed refractory epilepsy., Discussion: Reports of GM3SD outside the Amish population are rare, and whole-exome sequencing may be required to diagnose GM3SD in non-Amish patients. Since an effective treatment for GM3SD has not yet been established, we might select deep brain stimulation as a symptomatic treatment for involuntary movements in GM3SD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

GM3 synthase (GM3S) is a sialyltransferase that transfers sialic acid from CMP-sialic acid to lactosylceramide. This reaction results in formation of ganglioside GM3 and is essential for biosynthesis of its downstream derivatives, which include a- and b-series gangliosides. Here, we describe a method for GM3S enzymatic assay using fluorescence-labeled alkyl lactoside as acceptor substrate, followed by HPLC for separation of enzymatic product. The method allows quantitative assay of GM3S sialyltransferase activity in cultured cells and mouse brain tissues., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

GM3, a precursor for synthesis of a- and b-series gangliosides, is elevated in adipocytes of obese model animals and in sera of obese human patients with type 2 diabetes and/or dyslipidemia. GM3 synthase (GM3S)-KO C57BL/6 mice display enhanced insulin sensitivity and reduced development of high-fat diet-induced insulin resistance. However, the pathophysiological roles of GM3 and related gangliosides in the central control of feeding and metabolism remain unclear. We found that a mouse model (KKAy GM3S KO) generated by KO of the GM3S gene in the yellow obese strain, KKAy, displayed significant amelioration of obese phenotype. Whereas KKAy mice were hyperphagic and developed severe obesity, KKAy GM3S KO mice had significantly lower body weight and food intake, and greater glucose and insulin tolerance. The hypothalamic response to intraperitoneal administration of leptin was greatly reduced in KKAy mice, but was retained in KKAy GM3S KO mice. In studies of a cultured mouse hypothalamic neuronal cell line, enhanced leptin-dependent phosphorylation of ERK was observed in GM3S-deficient cells. Furthermore, KKAy GM3S KO mice did show altered coat color, suggesting that GM3S is also involved in melanocortin signaling. Our findings, taken together, indicate that GM3-related gangliosides play key roles in leptin and melanocortin signaling., (Copyright © 2018 Inamori et al.)

Since the successful molecular cloning in 1998 of GM3 synthase (GM3S, ST3GAL5), the enzyme responsible for initiating biosynthesis of all complex gangliosides, the efforts of our research group have been focused on clarifying the physiological and pathological implications of gangliosides, particularly GM3. We have identified isoforms of GM3S proteins having distinctive lengths of N-terminal cytoplasmic tails, and found that these cytoplasmic tails define subcellular localization, stability, and in vivo activity of GM3S isoforms. Our studies of the molecular pathogenesis of type 2 diabetes, focused on interaction between insulin receptor and GM3 in membrane microdomains, led to a novel concept: type 2 diabetes and certain other lifestyle-related diseases are membrane microdomain disorders resulting from aberrant expression of gangliosides. This concept has enhanced our understanding of the pathophysiological roles of GM3 and related gangliosides in various diseases involving chronic inflammation, such as insulin resistance, leptin resistance, and T-cell function and immune disorders (e.g., allergic asthma). We also demonstrated an essential role of GM3 in murine and human auditory systems; a common pathological feature of GM3S deficiency is deafness. This is the first direct link reported between gangliosides and auditory functions., (Copyright © 2017. Published by Elsevier Inc.)

GM3, a major lipid component of the plasma membrane outer leaflet in mammalian cells, is synthesized in the luminal side of Golgi by ST3GAL5 protein (ST3G5), a type II membrane protein. Two strains of St3Gal5 knockout mice have been established for studies of GM3 physiological function: St3Gal5-Ex5-KO (lacking exon 5, which contains the catalytic domain of ST3G5), and St3Gal5-Ex3-KO (lacking exon 3, which contains the initiation codons). Results of the present study demonstrate that GM3 synthesis is still present, at a low level, in liver of St3Gal5-Ex3-KO mice. St3Gal5 has two mRNA transcriptional variants: a-type and b-type. When exon 3 is deleted, ST3G5 is not translated from a-type or b-type, as a result of initiation codon deletion or frame shift. Through NCBI database search and real-time PCR analyses of various mouse tissues, we identified a liver-specific St3Gal5 transcriptional variant (c-type) capable of producing artificial ST3G5 (M*-ST3G5) having GM3 synthase activity in the absence of exon 3. St3Gal5-Ex3-KO mice expressed c-type mRNA without exon 3 (c-type -/- ) in liver. The transmembrane and catalytic domains of M*-ST3G5 translated from c-type -/- were identical to those from wild-type, although the cytoplasmic regions differed. Expression of M*-ST3G5 in embryonic fibroblasts derived from St3Gal5-Ex3-KO mice led to GM3 synthesis; M*-ST3G5 thus displayed enzyme activity in vivo. Taken together, our findings indicate that expression of liver-specific c-type variant accounts for the residual GM3 synthase activity observed in liver of St3Gal5-Ex3-KO mice.

Glycosphingolipids (GSLs) are abundant in plasma membranes of mammalian cells, and their synthesis is strictly regulated in the Golgi apparatus. Disruption of GSL homeostasis is the cause of numerous diseases. Hundreds of molecular species of GSLs exist, and the detailed mechanisms underlying their homeostasis remain unclear. We investigated the physiological significance of isoform production for β1,4-N-acetyl-galactosaminyl transferase 1/B4GALNT1 (B4GN1), an enzyme involved in synthesis of ganglio-series GSLs GM2/GD2/GA2. We discovered a new mRNA variant (termed variant 2) of B4GN1 through EST clone search. A new isoform, M1-B4GN1, which has an NH 2 -terminal cytoplasmic tail longer than that of previously-known isoform M2-B4GN1, is translated from variant 2. M1-B4GN1 has R-based motif (a retrograde transport signal) in the cytoplasmic tail. M1-B4GN1 is partially localized in the endoplasmic reticulum (ER) depending on the R-based motif, whereas M2-B4GN1 is localized in the Golgi. Stability of M1-B4GN1 is higher than that of M2-B4GN1 because of the R-based motif. M2-B4GN1 forms a homodimer via disulfide bonding. When M1-B4GN1 and M2-B4GN1 were co-expressed in CHO-K1 cells, the two isoforms formed a heterodimer. The M1/M2-B4GN1 heterodimer was more stable than the M2-B4GN1 homodimer, but the heterodimer was not transported from the Golgi to the ER. Our findings indicate that stabilization of M1-B4GN1 homodimer and M1/M2-B4GN1 heterodimer by R-based motif is related to prolongation of Golgi retention, but not to retrograde transport from the Golgi to the ER. Coexistence of several B4GN1 isoforms having distinctive characteristics presumably helps maintain overall enzyme stability and GSL homeostasis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aims: To evaluate the relationship between the apparent diffusion coefficient (ADC) value for bladder cancer and the recurrence/progression risk of post-transurethral resection (TUR)., Methods: Forty-one patients with initial and non-muscle-invasive bladder cancer underwent MRI from 2009 to 2012. Two radiologists measured ADC values. A pathologist calculated the recurrence/progression scores, and risk was classified based on the scores. Pearson's correlation was used to analyze the correlations of ADC value with each score and with each risk group, and the optimal cut-off value was established based on receiver operating characteristic (ROC) curve analysis. Furthermore, the relationship between actual recurrence / progression of cases and ADC values was examined by Unpaird U test., Results: There were significant correlations between ADC value and the recurrence score as well as the progression score (P<0.01, P<0.01, respectively). There were also significant correlations between ADC value and the recurrence risk group as well as progression risk group (P=0.042, P<0.01, respectively). The ADC cut-off value on ROC analysis was 1.365 (sensitivity 100%; specificity 97.4%) for the low and intermediate recurrence risk groups, 1.024 (sensitivity 47.4%; specificity 100%) for the intermediate and high recurrence risk groups, 1.252 (sensitivity 83.3%; specificity 81.3%) for the low and intermediate progression risk groups, and 0.955 (sensitivity 87.5%; specificity 63.2%) between the intermediate and high progression risk groups. The difference between the ADC values of the recurrence and nonrecurrence group in Unpaired t test was significant (P<0.05)., Conclusion: ADC on MRI in bladder cancer could potentially be useful, non-invasive measurement for estimating the risks of recurrence and progression.

Purpose: Our aim was to assess the usefulness of a new magnetic resonance imaging (MRI) finding, the placental recess, for diagnosing placental invasion., Methods: This retrospective study included 51 patients (mean age 34.1 years, range 26-43 years) with suspected placental invasion who underwent cesarean section. Preoperative MRI was performed using a 1.5-T unit and included axial, sagittal, and coronal T2-weighted imaging (T2WI) with half-Fourier fast spin-echo sequences. Overall, 9 patients showed placental invasion, and 42 did not. Placental recess was defined as a placental deformity with contraction of the placental surface and outer rim of the uterus accompanied by a T2 dark band. Two radiologists independently assessed the presence of the placental recess and conventional findings including uterine bulging, abnormal placental vascularity, placental heterogeneous intensity on T2-weighted imaging (T2WI), and the T2 dark band. Fisher's two-sided exact test was used to compare findings between patients with and without placental invasion. Interobserver reliability was assessed using the kappa statistic., Results: MRI features had interobserver reliability of >0.40. Placental recess yielded the highest kappa value (0.898). Significant differences were identified between patients with and without placental invasion regarding abnormal placental vascularity, placental heterogeneous intensity, a T2 dark band, and the placental recess on T2WI (p = 0.0282, 0.0003, 0.0003, <0.0001, respectively). The placental recess had sensitivity, specificity, positive and negative predictive values, and accuracy of 56, 100, 100, 91, and 92%, respectively., Conclusion: The placental recess was useful for diagnosing placental invasion, with high interobserver variability and accuracy.

We recently reported an increase in dicentric chromosome (DIC) formation after a single computed tomography (CT) scan (5.78-60.27 mSv: mean 24.24 mSv) and we recommended analysis of 2000 metaphase cells stained with Giemsa and centromere-FISH for dicentric chromosome assay (DCA) in cases of low-dose radiation exposure. In the present study, we analyzed the frequency of chromosome translocations using stored Carnoy's-fixed lymphocyte specimens from the previous study; these specimens were from 12 patients who were subject to chromosome painting of Chromosomes 1, 2 and 4. Chromosomes 1, 2 and 4 were analyzed in ∼5000 cells, which is equivalent to the whole-genome analysis of almost 2000 cells. The frequency of chromosome translocation was higher than the number of DICs formed, both before and after CT scanning. The frequency of chromosome translocations tended to be higher, but not significantly higher, in patients with a treatment history compared with patients without such a history. However, in contrast to the results for DIC formation, the frequency of translocations detected before and after the CT scan did not differ significantly. Therefore, analysis of chromosome translocation may not be a suitable assay for detecting chromosome aberrations in cases of low-dose radiation exposure from a CT scan. A significant increase in the frequency of chromosome translocations was not likely to be detected due to the high baseline before the CT scan; the high and variable frequency of translocations was probably due to multiple confounding factors in adults., (© The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Purpose: To compare the diagnostic accuracy of whole-body PET/CT and integrated PET/MR in relation to the total scan time durations., Methods: One hundred and twenty-three (123) patients (40 males and 83 females; mean age 59.6 years; range 20-83 years) with confirmed primary cancer and clinical suspicion of metastatic disease underwent whole-body 18F-FDG-PET/CT and 18F-FDG-PET/MR. Data acquisition was done after intravenous administration of 110-301 MBq radioactivity of 18F-FDG, and PET/MR data were acquired after the PET/CT data acquisition. The mean uptake times for PET/CT and PET/MR acquisition were 68.0 ± 8.0 and 98.0 ± 14 min, respectively. Total scan time was 20.0 and 25.0 min for whole-body PET/CT and PET/MR imaging., Results: The reconstructed PET/CT and PET/MR data detected 333/355 (93.8 %) common lesions in 111/123 (90.2 %) patients. PET/CT and PET/MR alone detected 348/355 and 340/355 lesions, respectively. No significant (p = 0.08) difference was observed for the overall detection efficiency between the two techniques. On the other hand, a significant difference was observed between the two techniques for the detection of lung (p = 0.003) and cerebrospinal (p = 0.007) lesions. The 15 lesions identified by PET/CT only included 8 lung, 3 lymph nodes, 2 bone, and 1 each of peritoneal and adrenal gland lesions. On the other hand, 7 (6 brain metastatic lesions and 1 bone lesion) were identified by PET/MR only., Conclusion: Integrated PET/MR is a feasible whole-body imaging modality and may score better than PET/CT for the detection of brain metastases. To further prove diagnostic utility, this technique requires further clinical validation.

In the Golgi maturation model, the Golgi cisternae dynamically mature along a secretory pathway. In this dynamic process, glycosyltransferases are transported from the endoplasmic reticulum (ER) to the Golgi apparatus where they remain and function. The precise mechanism behind this maturation process remains unclear. We investigated two glycosyltransferases, ST3Gal5 (ST3G5) and B4GalNAcT1 (B4GN1), involved in ganglioside synthesis and examined their signal sequences for ER export and Golgi retention. Reports have suggested that the [R/K](X)[R/K] motif functions as an ER exporting signal; however, this signal sequence is insufficient in stably expressed, full-length ST3G5. Through further analysis, we have clarified that the (2)R(3)R(X)(5) (9)K(X)(3) (13)K sequence in ST3G5 is essential for ER export. We have named the sequence the R/K-based motif. On the other hand, for ER export of B4GN1, the homodimer formation in addition to the R/K-based motif is required for ER export suggesting the importance of unidentified lumenal side interaction. We found that ST3G5 R2A/R3A and K9A/K13A mutants localized not only in Golgi apparatus but also in endosomes. Furthermore, the amounts of mature type asparagine-linked (N)-glycans in ST3G5 R2A/R3A and K9A/K13A mutants were decreased compared with those in wild-type proteins, and the stability of the mutants was lower. These results suggest that the R/K-based motif is necessary for the Golgi retention of ST3G5 and that the retention is involved in the maturation of N-glycans and in stability. Thus, several basic amino acids located on the cytoplasmic tail of ST3G5 play important roles in both ER export and Golgi retention., (© The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The Drosophila Toll pathway plays important roles in innate immune responses against Gram-positive bacteria and fungi. To identify previously uncharacterized components of this pathway, we performed comparative, ex vivo, genome-wide RNA interference screening. In four screens, we overexpressed the Toll adaptor protein dMyd88, the downstream kinase Pelle, or the nuclear factor κB (NF-κB) homolog Dif, or we knocked down Cactus, the Drosophila homolog of mammalian inhibitor of NF-κB. On the basis of these screens, we identified the E3 ubiquitin ligase Sherpa as being necessary for the activation of Toll signaling. A loss-of-function sherpa mutant fly exhibited compromised production of antimicrobial peptides and enhanced susceptibility to infection by Gram-positive bacteria. In cultured cells, Sherpa mediated ubiquitylation of dMyd88 and Sherpa itself, and Sherpa and Drosophila SUMO (small ubiquitin-like modifier) were required for the proper membrane localization of an adaptor complex containing dMyd88. These findings highlight a role for Sherpa in Drosophila host defense and suggest the SUMOylation-mediated regulation of dMyd88 functions in Toll innate immune signaling., (Copyright © 2015, American Association for the Advancement of Science.)

Purpose: The accident at the Fukushima Daiichi Nuclear Power Plant has raised concerns about radiation exposure, including medical radiation exposure such as X-ray and CT, in residents of Fukushima., Materials and Methods: We compared the numbers and the ratio of outpatients less than 10 years old who underwent imaging examinations [e.g., CT, X-ray, MRI, ultrasonography (US), etc.] at Fukushima Medical University hospital in Fukushima, Japan before (April 1, 2008-March 31, 2011) and after (April 1, 2011-March 31, 2014) the accident., Results: The number of outpatients less than 10 years old decreased after the accident. The number of outpatients less than 10 years old who underwent CT and X-ray examinations also significantly decreased after the accident (p < 0.001, p < 0.01, respectively)., Conclusion: Our results suggest that the number of pediatric radiological examinations decreased after the accident in Fukushima. We should continue to communicate with patients and their families to ensure that they understand the risks and benefits of radiological imaging in order to overcome their concerns about the nuclear disaster.

Excess risk of leukemia and brain tumors after CT scans in children has been reported. We performed dicentric chromosome assay (DCAs) before and after CT scan to assess effects of low-dose ionizing radiation on chromosomes. Peripheral blood (PB) lymphocytes were collected from 10 patients before and after a CT scan. DCA was performed by analyzing either 1,000 or 2,000 metaphases using both Giemsa staining and centromere-fluorescence in situ hybridization (Centromere-FISH). The increment of DIC formation was compared with effective radiation dose calculated using the computational dosimetry system, WAZA-ARI and dose length product (DLP) in a CT scan. Dicentric chromosome (DIC) formation increased significantly after a single CT scan, and increased DIC formation was found in all patients. A good correlation between the increment of DIC formation determined by analysis of 2,000 metaphases using Giemsa staining and those by 2,000 metaphases using Centromere-FISH was observed. However, no correlation was observed between the increment of DIC formation and the effective radiation dose. Therefore, these results suggest that chromosome cleavage may be induced by one CT scan, and we recommend 2,000 or more metaphases be analyzed in Giemsa staining or Centromere-FISH for DCAs in cases of low-dose radiation exposure.

Objective: The aim of the present study is to elucidate factors contributing to early recovery of urinary continence after robot-assisted laparoscopic radical prostatectomy (RARP) from the perspective of urethral and vesical anatomical features after RARP., Patients and Methods: Sixty consecutive patients undergoing RARP also underwent pre- and postoperative urethrovesicography (UVG). Both pre- and postoperative UVG evaluated the posterior-urethral vesical angle and position of the urethrovesical junction. Postoperative UVG was performed 7 days after RARP and also evaluated postoperative membranous urethral length (MUL) and the postoperative degree of atony of the external urethral sphincter. Associations were analyzed between pre- or postoperative UVG variables and urinary incontinence as well as between UVG variables significantly correlating with urinary incontinence and neurovascular bundle-preservation procedures., Results: Postoperative MUL was the only factor significantly associated with the state of continence in the early postoperative period according to multivariate logistic regression analysis (odds ratio, 1.94; 95% confidence interval, 1.22-3.12; p<0.005). A cutoff value of 17 mm offered the best accuracy in receiver operating characteristics analysis. Postoperative MUL was significantly increased in the group with preservation of the neurovascular bundle (p=0.01)., Conclusions: Postoperative MUL is the most important factor for recovery of urinary continence in the early postoperative period after RARP. Postoperative MUL >17 mm as measured on UVG can be expected to predict early recovery of urinary continence. Postoperative MUL was greater with preservation of the neurovascular bundle, thus allowing early recovery of urinary continence.

Purpose: To validate the use of bone scintigraphy (BS) versus computed tomography (CT) for therapeutic monitoring in patients during treatment with zoledronic acid., Materials and Methods: Eleven patients with bone-only metastatic disease and being treated with zoledronic acid were included. The effects of therapies including chemotherapy and hormone therapy were evaluated in 25 separate examinations in total as follows: complete response (CR), when no bone metastasis was visible; partial response (PR), when a decrease in the lesion area was detected; stable disease (SD), when no or slight change was observed; and progressive disease (PD), when new or enlarged lesion areas were observed., Results: The accuracies of examination by Readers 1, 2, and 3 respectively were 76%, 80% and 76% for BS, 52%, 48%, and 40% for CT, and 64%, 52% and 60% for BS and CT combined with Readers 2 and 3 observing significant differences between CT and BS results. The rates of interobserver agreement between Readers 1 and 2, between Readers 1 and 3, and between Reader 2 and 3 respectively, were 84%, 80% and 88% (κ = 0.648, 0.561 and 0.766) for BS, 52%, 56%, and 60% (κ = 0.180, 0.278 and 0.282) for CT, and 52%, 60%, and 56% (κ = 0.215, 0.282 and 0.232) for CT and BS combined., Conclusion: BS is effective for assessing the response of bone metastasis to therapy in patients during zoledronic acid treatment.

Purpose: Computed tomography (CT)-guided radiofrequency ablation (RFA) is safe and effective for patients with unresectable primary, recurrent, or metastatic thoracic malignancies. Several studies have shown the benefit of employing 18-fluoro-deoxyglucose positron-emission tomography (FDG-PET) to follow thoracic malignancies treated with RFA. In this prospective study, we show the safety and therapeutic efficacy of RFA and the utility of FDG-PET as tool for early detection of local recurrence., Methods: Twenty patients were enrolled in this study, and 24 lesions were ablated. Seven lesions were primary lung cancer, and 17 lesions were recurrent tumors or metastases from extrathoracic sites. Tumor size was in the range of 0.4-3.3 cm in diameter (mean: 1.5 cm). CT and FDG-PET scans were scheduled 7-14 days and 3-6 months after RFA treatment., Results: There were 17 adverse events (70.8 %) in 24 ablations included 13 pneumothoraces, two cases of chest pain, and two episodes of fever. With a median follow-up of 35.9 months (range 1-62 months), the overall 2-year survival rate was 84.2 %. Local recurrence occurred at four sites (2-year local control rate was 74.3 %). The FDG-PET results 7-14 days after RFA did not predict recurrence, whereas positive findings 3-6 months after RFA significantly correlated with local recurrence (p = 0.0016)., Conclusions: We confirmed the effectiveness of RFA for unresectable primary and secondary thoracic malignancies. FDG-PET analysis 3-6 months after ablation is a useful tool to assess local control.