再発性甲状腺癌のリンパ節転移におけるTc-99m MDPの集積(Tc-99m MDP Accumulation in Lymph Node Metastases of Recurrent Thyroid Cancer)(英語)

金沢医科大学 放射線科原著論文/症例報

Local relapse of nasopharyngeal cancer and Voxel-based analysis of FMISO uptake using PET with semiconductor detectors

Background: Hypoxic cancer cells are thought to be radioresistant and could impact local recurrence after radiotherapy (RT). One of the major hypoxic imaging modalities is [18F]fluoromisonidazole positron emission tomography (FMISO-PET). High FMISO uptake before RT could indicate radioresistant sites and might be associated with future local recurrence. The predictive value of FMISO-PET for intra-tumoral recurrence regions was evaluated using high-resolution semiconductor detectors in patients with nasopharyngeal carcinoma after intensity-modulated radiotherapy (IMRT). Methods: Nine patients with local recurrence and 12 patients without local recurrence for more than 3 years were included in this study. These patients received homogeneous and standard doses of radiation to the primary tumor irrespective of FMISO uptake. The FMISO-PET image before RT was examined via a voxel-based analysis, which focused on the relationship between the degree of FMISO uptake and recurrence region. Results: In the pretreatment FMISO-PET images, the tumor-to-muscle ratio (TMR) of FMISO in the voxels of the tumor recurrence region was significantly higher than that of the non-recurrence region (p < 0.0001). In the recurrent patient group, a TMR value of 1.37 (95% CI: 1.36-1.39) corresponded to a recurrence rate of 30%, the odds ratio was 5.18 (4.87-5.51), and the area under the curve (AUC) of the receiver operating characteristic curve was 0.613. In all 21 patients, a TMR value of 2.42 (2.36-2.49) corresponded to an estimated recurrence rate of 30%, and the AUC was only 0.591. Conclusions: The uptake of FMISO in the recurrent region was significantly higher than that in the non-recurrent region. However, the predictive value of FMISO-PET before IMRT is not sufficient for up-front dose escalation for the intra-tumoral high-uptake region of FMISO. Because of the higher mean TMR of the recurrence region, a new hypoxic imaging method is needed to improve the sensitivity and specificity for hypoxia

A novel locally operated master-slave robot system for single-incision laparoscopic surgery

Purpose: Single-incision laparoscopic surgery (SILS) provides more cosmetic benefits than conventional laparoscopic surgery but presents operational difficulties. To overcome this technical problem, we have developed a locally operated master-slave robot system that provides operability and a visual field similar to conventional laparoscopic surgery. Material and methods: A surgeon grasps the master device with the left hand, which is placed above the abdominal wall, and holds a normal instrument with the right hand. A laparoscope, a slave robot, and the right-sided instrument are inserted through one incision. The slave robot is bent in the body cavity and its length, pose, and tip angle are changed by manipulating the master device; thus the surgeon has almost the same operability as with normal laparoscopic surgery. To evaluate our proposed system, we conducted a basic task and an ex vivo experiment. Results: In basic task experiments, the average object-passing task time was 9.50 sec (SILS cross), 22.25 sec (SILS parallel), and 7.23 sec (proposed SILS). The average number of instrument collisions was 3.67 (SILS cross), 14 (SILS parallel), and 0.33 (proposed SILS). In the ex vivo experiment, we confirmed the applicability of our system for single-port laparoscopic cholecystectomy. Conclusion: We demonstrated that our proposed robot system is useful for single-incision laparoscopic surgery.ArticleMINIMALLY INVASIVE THERAPY & ALLIED TECHNOLOGIES. 23(6):326-332 (2014)journal articl

Computational Prediction of O-linked Glycosylation Sites That Preferentially Map on Intrinsically Disordered Regions of Extracellular Proteins

O-glycosylation of mammalian proteins is one of the important posttranslational modifications. We applied a support vector machine (SVM) to predict whether Ser or Thr is glycosylated, in order to elucidate the O-glycosylation mechanism. O-glycosylated sites were often found clustered along the sequence, whereas other sites were located sporadically. Therefore, we developed two types of SVMs for predicting clustered and isolated sites separately. We found that the amino acid composition was effective for predicting the clustered type, whereas the site-specific algorithm was effective for the isolated type. The highest prediction accuracy for the clustered type was 74%, while that for the isolated type was 79%. The existence frequency of amino acids around the O-glycosylation sites was different in the two types: namely, Pro, Val and Ala had high existence probabilities at each specific position relative to a glycosylation site, especially for the isolated type. Independent component analyses for the amino acid sequences around O-glycosylation sites showed the position-specific existences of the identified amino acids as independent components. The O-glycosylation sites were preferentially located within intrinsically disordered regions of extracellular proteins: particularly, more than 90% of the clustered O-GalNAc glycosylation sites were observed in intrinsically disordered regions. This feature could be the key for understanding the non-conservation property of O-glycosylation, and its role in functional diversity and structural stability

Retrospective chart review of oral somatic delusions

Objective: Oral cenesthopathy is characterized by foreign body sensations without medical and dental evidence for them. It is thought to be a rare disease in psychiatry, but many patients are visiting dental clinics seeking treatment to remove a foreign body. Even though the features of oral cenesthopathy might be different between a psychiatric clinic and a dental clinic, there has been no clinico-statistical study from dentists. In this study, we report a clinico-statistical study of patients with oral cenesthopathy in dentistry. Methods: This is a retrospective chart review of 606 outpatients with oral cenesthopathy in Tokyo Medical and Dental University from April 2010 through to March 2015. Results: A total of 159 male and 447 female patients were included in this study. The mean age was 62.08 years, and female patients were older than male patients. The trigger of the dental treatment and the acute phase of depression at the onset were significantly related (p=0.037). Only 128 patients (36%) had clinically significant improvement after 6 months of pharmacotherapy. No history of psychiatric disorders (odds ratio [OR] 0.479 [95% confidence interval {CI}: 0.262–0.875], p=0.017) and longer duration of illness (>18 months) (OR 2.626 [95% CI: 1.437–4.799], p=0.002) were significant factors for clinical outcomes. Conclusion: Patients with oral cenesthopathy in our clinic were predominantly elderly female patients. Dental treatment in the acute phase of depression might be a risk factor for oral cenesthopathy. Therefore, comprehending the situation of psychiatric disorder and obtaining adequate informed consent might be required to prevent the trouble concerning oral cenesthopathy

TIGIT/CD155 axis mediates resistance to immunotherapy in patients with melanoma with the inflamed tumor microenvironment

Background Patients with cancer benefit from treatment with immune checkpoint inhibitors (ICIs), and those with an inflamed tumor microenvironment (TME) and/or high tumor mutation burden (TMB), particularly, tend to respond to ICIs; however, some patients fail, whereas others acquire resistance after initial response despite the inflamed TME and/or high TMB. We assessed the detailed biological mechanisms of resistance to ICIs such as programmed death 1 and/or cytotoxic T-lymphocyte-associated protein 4 blockade therapies using clinical samples. Methods We established four pairs of autologous tumor cell lines and tumor-infiltrating lymphocytes (TILs) from patients with melanoma treated with ICIs. These tumor cell lines and TILs were subjected to comprehensive analyses and in vitro functional assays. We assessed tumor volume and TILs in vivo mouse models to validate identified mechanism. Furthermore, we analyzed additional clinical samples from another large melanoma cohort. Results Two patients were super-responders, and the others acquired resistance: the first patient had a non-inflamed TME and acquired resistance due to the loss of the beta-2 microglobulin gene, and the other acquired resistance despite having inflamed TME and extremely high TMB which are reportedly predictive biomarkers. Tumor cell line and paired TIL analyses showed high CD155, TIGIT ligand, and TIGIT expression in the tumor cell line and tumor-infiltrating T cells, respectively. TIGIT blockade or CD155-deletion activated T cells in a functional assay using an autologous cell line and paired TILs from this patient. CD155 expression increased in surviving tumor cells after coculturing with TILs from a responder, which suppressed TIGIT+ T-cell activation. Consistently, TIGIT blockade or CD155-deletion could aid in overcoming resistance to ICIs in vivo mouse models. In clinical samples, CD155 was related to resistance to ICIs in patients with melanoma with an inflamed TME, including both primary and acquired resistance. Conclusions The TIGIT/CD155 axis mediates resistance to ICIs in patients with melanoma with an inflamed TME, promoting the development of TIGIT blockade therapies in such patients with cancer

シニクコウ シンシュツエキ チュウ ノ バイオマーカー オ モチイタ シシュウビョウ シンダン

Periodontal diseases cause an inflammation and degradation of periodontal tissues and missing of teeth. The incidence rate of periodontal diseases is high in middle-aged and elderly people. A reasonable diagnosis of periodontal diseases is very important to keep teeth, however, conventional examinations of periodontal diseases is not necessarily exact and objective. Gingival crevicular fluid (GCF) is an exudate secreted from periodontal tissues and contains many components including proteolytic enzymes, inflammatory cytokines, blood-associated proteins, cellular and bacterial fragments. Because some proteins in GCF are related to inflammation, tissue degradation and bone metabolism, those proteins have been studying as a diagnostic marker of periodontal diseases. GCF is noninvasively collected using a sterile paper strip and biomarkers are determined using enzyme-linked immunosorbent assay (ELISA) and enzyme activity assay. We identified calprotectin, an inflammationrelated protein, in GCF and calprotectin level in GCF from periodontitis sites was significantly higher than that of healthy control. Calprotectin level in GCF was positively correlated to gingival index and other biomarkers and decreased by periodontal treatments. Resistin is an adipocytokine and its level increases in some inflammatory diseases. Resistin level in GCF from periodontitis sites was high compared to the level of healthy control samples. Procollagen type I C-terminal peptide (PICP) is a biomarker for bone metabolism and its level was high in GCF collected from periodontitis sites. These results suggested that calprotectin, resistin and PICP are useful biomarkers for periodontal diseases. On the other hand, we showed that glycated albumin (GA), a marker of diabetes mellitus (DM), was contained in GCF and GA level in GCF from DM patients was significantly higher than that of non-DM individuals. Components in GCF may be biomarkers of systemic diseases as well as periodontal diseases and their determination will be useful diagnostic examination of some diseases. Recently, we have been studying the determining system of GCF calprotectin, including microchip ELISA, surface plasmon resonance assay and immuno-chromatography assay. When GCF biomarkers are determined using the determining systems, we will simply, exactly and objectively diagnose periodontal diseases at our dental offices

Adaptive Optics Spectroscopy of the [Fe II] Outflows from HL Tauri and RW Aurigae

We present new results of [Fe II] 1.644-micron spectroscopy toward the jets from HL Tau and RW Aur carried out with the Subaru Telescope combined with the adaptive optics system. We observed the regions within 2" - 3" from the stars with the sub-arcsecond resolutions of 0."5 and 0."2 for HL Tau and RW Aur, respectively. In addition to the strong, high velocity emission extended along each jet, we detected a blueshifted low velocity emission feature seen as a wing or shoulder of the high velocity emission at each stellar position. Detailed analysis shows that the position-velocity diagrams (PVDs) of HL Tau and RW Aur show a characteristic similar to those of the cold disk wind and X-wind models in that the [Fe II] line width is broad in the vicinity of the stellar position and is narrower at the extended jet. A closer comparison suggests, however, that the disk wind model tends to have too large line width at the jet while the X-wind model has excess emission on the redshifted side at the stellar position. The narrow velocity width with symmetric line profiles of the observed high velocity emission supports an X-wind type model where the launching region is localized in a small radial range, while the low velocity emission located away from the star favors the presence of a disk wind. The [Fe II] emission from the HL Tau jet shows a gap of 0."8 between the redshifted jet and the star, indicating the presence of an optically thick disk of ~ 160 AU in radius. The [Fe II] emission from the RW Aur jet shows a marked drop from the redshifted peak at Y ~ -0."2 toward the star, suggesting that its disk radius is smaller than 40 AU.Comment: Accepted in the ApJ (October 2006, v649n2), AAS LaTEX macros v 5.2, Total 25 pages with 7 figure