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This is an explanatory paper on Sun Il Kwon et al., Nat. Photon. 15: 914-918, 2021 and some parts of this manuscript are translated from the paper. Medical imaging modalities such as X-ray computed tomography, Magnetic resonance imaging, positron emission tomography (PET), and single photon emission computed tomography, require image reconstruction processes, consequently constraining them to form cylindrical shapes. However, among them, only PET can use additional information, so called time of flight, on an event-by-event basis. If coincidence time resolution (CTR) of PET detectors improved to 30 ps, which corresponds to spatial resolution of 4.5 mm, directly localizing electron-positron annihilation point is possible, allowing us to circumvent image reconstruction processes and free us from the geometric constraint. We call this concept direct positron emission imaging (dPEI). We have developed ultrafast radiation detectors by focusing on Cherenkov photon detection. Furthermore, the CTR of 32 ps being equivalent to 4.8 mm spatial resolution is achieved by combining deep learning-based signal processing with the detectors. In this article, we explain how we developed the detectors and demonstrated the first dPEI using different types of phantoms, how we will tackle limitations to be addressed to make the dPEI more practical, and how dPEI will emerge as an imaging modality in nuclear medicine.
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Procesamiento de Imagen Asistido por Computador , Tomografía de Emisión de Positrones , Procesamiento de Imagen Asistido por Computador/métodos , Fantasmas de Imagen , Fotones , Tomografía de Emisión de Positrones/instrumentación , Tomografía de Emisión de Positrones/métodos , Factores de TiempoRESUMEN
AIM: This retrospective cohort study aimed to compare the risk of serious infections in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor-α inhibitors (TNFαi) and interleukin-6 inhibitors (IL-6i), with no prior use of biological disease-modifying antirheumatic drugs (bDMARDs). METHODS: We employed the nationwide insurance claims database encompassing the years 2005 to 2018 in Japan. The inclusion criteria specified patients who were prescribed any type of bDMARDs, including TNFαi and IL-6i. The following exclusion criteria were applied: missing prescription dates, RA not diagnosed, below 16 years of age, bDMARDs prescribed within 6 months of registration, RA diagnosed post-bDMARDs prescription, and incidence of serious infections within 2 weeks before bDMARDs therapy. We applied stabilized inverse probability weights and utilized a Cox regression model to estimate the risk of serious infections associated with TNFαi and IL-6i. RESULTS: The cohort of 2493 patients with RA was categorized into a TNFαi group and an IL-6i group of 2018 and 475 participants, respectively. The median follow-up duration (interquartile range) was 347 (147-820) days in the TNFαi group and 369 (149-838) days in the IL-6i group. In the inverse probability-weighted cohort, the incidence rates (95% confidence interval) of serious infections were 2.13 (1.65-2.71) and 3.25 (2.15-4.69) per 100 person-years for the TNFαi and IL-6i groups, respectively. The hazard ratio (95% confidence interval) comparing the TNFαi group to the IL-6i group was 0.66 (0.36-1.20, p = 0.168). DISCUSSION: The results underscore the lack of evidence to preferentially favor either TNFαi or IL-6i as later-line therapy in the management of bDMARDs-naive RA to mitigate the risk of serious infections.
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Antirreumáticos , Artritis Reumatoide , Infecciones , Interleucina-6 , Factor de Necrosis Tumoral alfa , Humanos , Artritis Reumatoide/tratamiento farmacológico , Estudios Retrospectivos , Japón/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Incidencia , Interleucina-6/antagonistas & inhibidores , Antirreumáticos/efectos adversos , Antirreumáticos/uso terapéutico , Adulto , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Infecciones/epidemiología , Infecciones/inducido químicamente , Estudios de Cohortes , Inhibidores de la Interleucina-6 , Pueblos del Este de AsiaRESUMEN
Objective.In positron emission tomography (PET) reconstruction, the integration of time-of-flight (TOF) information, known as TOF-PET, has been a major research focus. Compared to traditional reconstruction methods, the introduction of TOF enhances the signal-to-noise ratio of images. Precision in TOF is measured by full width at half maximum (FWHM) and the offset from ground truth, referred to as coincidence time resolution (CTR) and bias.Approach.This study proposes a network combining transformer and convolutional neural network (CNN) to utilize TOF information from detector waveforms, using event waveform pairs as inputs. This approach integrates the global self-attention mechanism of Transformer, which focuses on temporal relationships, with the local receptive field of CNN. The combination of global and local information allows the network to assign greater weight to the rising edges of waveforms, thereby extracting valuable temporal information for precise TOF predictions. Experiments were conducted using lutetium yttrium oxyorthosilicate (LYSO) scintillators and silicon photomultiplier (SiPM) detectors. The network was trained and tested using the waveform datasets after cropping.Main results.Compared to the constant fraction discriminator (CFD), CNN, CNN with attention, long short-term memory (LSTM) and Transformer, our network achieved an average CTR of 189 ps, reducing it by 82 ps (more than 30%), 13 ps (6.4%), 12 ps (6.0%), 16 ps (7.8%) and 9 ps (4.6%), respectively. Additionally, a reduction of 10.3, 8.7, 6.7 and 4 ps in average bias was achieved compared to CNN, CNN with attention, LSTM and Transformer.Significance.This work demonstrates the potential of applying the Transformer for PET TOF estimation using real experimental data. Through the integration of both CNN and Transformer with local and global attention, it achieves optimal performance, thereby presenting a novel direction for future research in this field.
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Procesamiento de Imagen Asistido por Computador , Redes Neurales de la Computación , Tomografía de Emisión de Positrones , Tomografía de Emisión de Positrones/instrumentación , Tomografía de Emisión de Positrones/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Factores de TiempoRESUMEN
Direct positron emission imaging (dPEI), which does not require a mathematical reconstruction step, is a next-generation molecular imaging modality. To maximize the practical applicability of the dPEI system to clinical practice, we introduce a novel reconstruction-free image-formation method called direct µCompton imaging, which directly localizes the interaction position of Compton scattering from the annihilation photons in a three-dimensional space by utilizing the same compact geometry as that for dPEI, involving ultrafast time-of-flight radiation detectors. This unique imaging method not only provides the anatomical information about an object but can also be applied to attenuation correction of dPEI images. Evaluations through Monte Carlo simulation showed that functional and anatomical hybrid images can be acquired using this multimodal imaging system. By fusing the images, it is possible to simultaneously access various object data, which ensures the synergistic effect of the two imaging methodologies. In addition, attenuation correction improves the quantification of dPEI images. The realization of the whole reconstruction-free imaging system from image generation to quantitative correction provides a new perspective in molecular imaging.
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Procesamiento de Imagen Asistido por Computador , Método de Montecarlo , Fantasmas de Imagen , Tomografía de Emisión de Positrones , Procesamiento de Imagen Asistido por Computador/métodos , Tomografía de Emisión de Positrones/métodos , Tomografía de Emisión de Positrones/instrumentación , Algoritmos , Humanos , Simulación por ComputadorRESUMEN
Podoplanin (PDPN) is a prognostic factor and is involved in several mechanisms of tumor progression in human squamous cell carcinoma (SCC). Canine non-tonsillar SCC (NTSCC) is a common oral tumor in dogs and has a highly invasive characteristic. In this study, we investigated the function of PDPN in canine NTSCC. In canine NTSCC clinical samples, PDPN overexpression was observed in 80% of dogs with NTSCC, and PDPN expression was related to ki67 expression. In PDPN knocked-out canine NTSCC cells, cell proliferation, cancer stemness, and migration were suppressed. As the mechanism of PDPN-mediated cell proliferation, PDPN knocked-out induced apoptosis and G2/M cell cycle arrest in canine NTSCC cells. These findings suggest that PDPN promotes tumor malignancies and may be a novel biomarker and therapeutic target for canine NTSCC.
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Carcinoma de Células Escamosas , Enfermedades de los Perros , Animales , Perros , Humanos , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/veterinaria , Proliferación Celular , BiomarcadoresRESUMEN
Mucosal melanoma metastasizes at an early stage of the disease in human and dog. We revealed that overexpression of podoplanin in tumor invasion fronts (IF) was related to poor prognosis of dogs with mucosal melanoma. Moreover, podoplanin expressed in canine mucosal melanoma cells promotes proliferation and aggressive amoeboid invasion by activating Rho-associated kinase (ROCK)-myosin light chain 2 (MLC2) signaling. PDPN-ROCK-MLC2 signaling plays a role in cell-cycle arrest and cellular senescence escape as a mechanism for regulating proliferation. Podoplanin induces amoeboid invasion in the IFs of mouse xenografted tumor tissues, similar to canine mucosal melanoma clinical samples. We further identified that podoplanin expression was related to poor prognosis of human patients with mucosal melanoma, and human mucosal melanoma with podoplanin-high expression enriched gene signatures related to amoeboid invasion, similar to canine mucosal melanoma. Overall, we propose that podoplanin promotes canine and human mucosal melanoma metastasis by inducing aggressive amoeboid invasion and naturally occurring canine mucosal melanoma can be a novel research model for podoplanin expressing human mucosal melanoma. IMPLICATIONS: Podoplanin could be a new therapeutic target to restrict the metastatic dissemination of canine and human mucosal melanoma.
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Amoeba , Melanoma , Humanos , Perros , Animales , Ratones , Melanoma/patología , Factores de Transcripción , Transducción de Señal , Línea Celular TumoralRESUMEN
AIMS: This retrospective cohort study aimed to evaluate the effect of the interaction between methotrexate and glucocorticoids on the risk of developing bacterial infections in patients with rheumatoid arthritis (RA) using biological disease-modifying antirheumatic drugs (bDMARDs). METHODS: We used the 2005-2018 JMDC claims database, a nationwide claims database in Japan. From the database of 7 175 048 patients, study patients were obtained by applying the following exclusion criteria: no use of bDMARDs; without information on the date of prescription; without RA as a disease; other than the new users of bDMARDs; and age <18 years. The exposures were glucocorticoids and methotrexate, and the outcome was bacterial infection. The interaction effects were examined using multivariate Cox regression analysis. Bacterial infections were identified according to antibiotic prescription and International Statistical Classification of Diseases and Related Health Problems, 10th revision codes. RESULTS: A total of 2837 RA patients were identified, with a median age of 50 years. The incidence of infection was 16.8% (95% confidence interval: 15.5-18.3). The interaction term for the doses of glucocorticoids and methotrexate was significant. Additionally, a higher dose of glucocorticoid was a significant risk factor for developing bacterial infections on the side of high doses of methotrexate. The incidence of bacterial infections tended to increase significantly with increasing methotrexate doses coprescribed with glucocorticoids ≥5 mg or glucocorticoid doses coprescribed with methotrexate ≥8 mg. CONCLUSION: Our results indicate a potential association between methotrexate dose and bacterial infections during bDMARDs administration with glucocorticoids in patients with RA.
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Antirreumáticos , Artritis Reumatoide , Infecciones Bacterianas , Productos Biológicos , Humanos , Persona de Mediana Edad , Adolescente , Metotrexato/efectos adversos , Glucocorticoides/efectos adversos , Estudios Retrospectivos , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/epidemiología , Antirreumáticos/efectos adversos , Factores Biológicos/uso terapéutico , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/tratamiento farmacológico , Productos Biológicos/uso terapéuticoRESUMEN
Purpose: Biologic disease-modifying anti-rheumatic drugs (bDMARDs) are highly effective and safe against juvenile idiopathic arthritis (JIA), which is classified into systemic JIA (sJIA) and the other JIA categories (non-sJIA) according to differences in clinical symptoms and pathophysiology. The purpose of the current study was to investigate trends in patterns of prescribing bDMARDs for moderate-to-severe JIA using a relatively large sample size in Japan. Patients and Methods: A descriptive epidemiological study based on a nationwide claims database in Japan was conducted from 2012 to 2018 using the "JMDC Claims Database" to explain annual changes based on the number of patients prescribed bDMARDs. Study drugs were identified based on the Anatomical Therapeutic Chemical codes, such as methotrexate, glucocorticoids, non-steroidal anti-inflammatory drugs, and bDMARDs. Results: From a database of 6,862,244 patients, the following exclusion criteria were applied: aged ≥16 years, without "M08" in their ICD-10 code as disease, and missing the information of prescription date in the database during the study period, resulting in a final number of 111 JIA patients. We found an increasing trend for adalimumab and tocilizumab and a decreasing trend for methotrexate. Differences in medication use between sJIA and non-sJIA patients were also evident, being consistent with national and international guidelines. Conclusion: Although the introduction of bDMARDs has markedly improved the efficacy of JIA therapy, there are still many short- and long-term safety issues to be examined, including the risk of infection and potential risk of associated malignancy. Future studies are needed to clarify these issues.
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Bevacizumab (BV) is a recombinant and humanized monoclonal antibody that inhibits vascular endothelial growth factor. BV is used to treat various types of cancer. Proteinuria is a characteristic adverse event that occurs as a result of treatment with BV. However, the onset timing of proteinuria after BV administration remains unclear. In the present study, we examined the risk factors affecting the timing of proteinuria onset upon BV administration. Medical records of 135 patients (62 males and 73 females; mean age: 67.8±10.7 years) treated with BV were reviewed at the Kindai University Nara Hospital from April 2011 to December 2019. Proteinuria was identified in 44.4% (60/135) of the studied patients. The time to the first onset of proteinuria was significantly shorter in the administration of doses of BV (≥10) and history of diabetes mellitus. The median cumulative dose associated with the onset of proteinuria was 30.0 (16.1-58.8) mg/kg. When this cumulative dose was compared with 10 mg/kg, no significant difference was observed (p=0.319). The present study demonstrated that the administration of doses of BV (≥10) and history of diabetes mellitus are one of the main risk factors for early-onset proteinuria. These findings may be useful for the future treatment of early-onset proteinuria in patients treated with BV.
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Neoplasias , Factor A de Crecimiento Endotelial Vascular , Anciano , Anticuerpos Monoclonales Humanizados/uso terapéutico , Bevacizumab/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Proteinuria/inducido químicamente , Proteinuria/tratamiento farmacológicoRESUMEN
Objective.Convolutional neural networks (CNNs) are a strong tool for improving the coincidence time resolution (CTR) of time-of-flight (TOF) positron emission tomography detectors. However, several signal waveforms from multiple source positions are required for CNN training. Furthermore, there is concern that TOF estimation is biased near the edge of the training space, despite the reduced estimation variance (i.e. timing uncertainty).Approach.We propose a simple method for unbiased TOF estimation by combining a conventional leading-edge discriminator (LED) and a CNN that can be trained with waveforms collected from one source position. The proposed method estimates and corrects the time difference error calculated by the LED rather than the absolute time difference. This model can eliminate the TOF estimation bias, as the combination with the LED converts the distribution of the label data from discrete values at each position into a continuous symmetric distribution.Main results.Evaluation results using signal waveforms collected from scintillation detectors show that the proposed method can correctly estimate all source positions without bias from a single source position. Moreover, the proposed method improves the CTR of the conventional LED.Significance.We believe that the improved CTR will not only increase the signal-to-noise ratio but will also contribute significantly to a part of the direct positron emission imaging.
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Fotones , Conteo por Cintilación , Redes Neurales de la Computación , Tomografía de Emisión de Positrones/métodos , Conteo por Cintilación/métodos , Relación Señal-RuidoRESUMEN
This is a review article on photon counting detector for radiation measurement by JSRT and JSMP (https://www.jsmp.org/en).
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Monitoreo de Radiación , Diagnóstico por Imagen , Fotones , Física , RadiografíaRESUMEN
Although supervised convolutional neural networks (CNNs) often outperform conventional alternatives for denoising positron emission tomography (PET) images, they require many low- and high-quality reference PET image pairs. Herein, we propose an unsupervised 3D PET image denoising method based on an anatomical information-guided attention mechanism. The proposed magnetic resonance-guided deep decoder (MR-GDD) utilizes the spatial details and semantic features of MR-guidance image more effectively by introducing encoder-decoder and deep decoder subnetworks. Moreover, the specific shapes and patterns of the guidance image do not affect the denoised PET image, because the guidance image is input to the network through an attention gate. In a Monte Carlo simulation of [18F]fluoro-2-deoxy-D-glucose (FDG), the proposed method achieved the highest peak signal-to-noise ratio and structural similarity (27.92 ± 0.44 dB/0.886 ± 0.007), as compared with Gaussian filtering (26.68 ± 0.10 dB/0.807 ± 0.004), image guided filtering (27.40 ± 0.11 dB/0.849 ± 0.003), deep image prior (DIP) (24.22 ± 0.43 dB/0.737 ± 0.017), and MR-DIP (27.65 ± 0.42 dB/0.879 ± 0.007). Furthermore, we experimentally visualized the behavior of the optimization process, which is often unknown in unsupervised CNN-based restoration problems. For preclinical (using [18F]FDG and [11C]raclopride) and clinical (using [18F]florbetapir) studies, the proposed method demonstrates state-of-the-art denoising performance while retaining spatial resolution and quantitative accuracy, despite using a common network architecture for various noisy PET images with 1/10th of the full counts. These results suggest that the proposed MR-GDD can reduce PET scan times and PET tracer doses considerably without impacting patients.
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Procesamiento de Imagen Asistido por Computador , Tomografía de Emisión de Positrones , Fluorodesoxiglucosa F18 , Humanos , Redes Neurales de la Computación , Relación Señal-RuidoRESUMEN
BACKGROUND AND OBJECTIVE: Biologic disease-modifying anti-rheumatic drugs (bDMARDs) are used either when conventional synthetic DMARDs are ineffective or when disease activity is high and with poor prognostic factors, based on various clinical guidelines. The purpose of this study was to investigate the prescribing trends of bDMARDs for patients with rheumatoid arthritis in Japan, and to clarify whether the pharmacological therapy of bDMARDs is administered based on guidelines. METHODS: We conducted a descriptive epidemiological study from 2012 to 2018 using the JMDC Claims Database, a nationwide claims database, and described the annual changes based on the number of patients prescribed bDMARDs. Anti-rheumatic drugs were identified based on the Anatomical Therapeutic Chemical codes, including methotrexate, glucocorticoids, non-steroidal anti-inflammatory drugs and bDMARDs. RESULTS: From the database including 6,862,244 people, the data of 6407 patients with rheumatoid arthritis were extracted. The present study demonstrated that the proportion of patients prescribed bDMARDs was 1.0 per 1000 people, with those aged ≥ 65 years being the most common age group. The proportion of patients with rheumatoid arthritis who were prescribed bDMARDs increased significantly over time (p < 0.0001). Additionally, the concomitant proportions of methotrexate (p < 0.0001), non-steroidal anti-inflammatory drugs (p < 0.0001) and glucocorticoids (p = 0.0001) prescribed with bDMARDs decreased significantly over time. CONCLUSIONS: The increase in bDMARD monotherapy may be attributed to the new bDMARDs that have been launched sequentially; furthermore, physicians have come to recognise monotherapy as the mainstay of treatment. Future studies must accumulate evidence on the long-term efficacy and safety of bDMARDs.
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Antirreumáticos , Artritis Reumatoide , Productos Biológicos , Antirreumáticos/uso terapéutico , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/epidemiología , Productos Biológicos/uso terapéutico , Humanos , Japón/epidemiología , Metotrexato/uso terapéuticoRESUMEN
This study aimed to investigate the relationship between renal dysfunction and electrolyte abnormalities, which are adverse events of foscarnet used for cytomegalovirus infection. Of the Ninety hematopoietic stem cell transplantation patients, 32 who met the selection criteria were enrolled in this retrospective study. The study patients were divided into two groups according to whether they developed renal dysfunction. The incidences of hypocalcemia, hypokalemia, and hypomagnesemia with an increase of grade 2 or higher in the renal dysfunction group were 45.5%, 18.2%, and 27.3%, respectively. Additionally, in the renal dysfunction group, a significant correlation was observed between creatinine and calcium (r = -0.458, p = 0.0244) and between creatinine and potassium (r = -0.520, p = 0.0092). This study shows that renal dysfunction and electrolyte abnormalities may be closely related in HSCT patients receiving foscarnet; thus, it is a report that may contribute to the safety of continuous foscarnet treatment.
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Antivirales/efectos adversos , Electrólitos/sangre , Foscarnet/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Insuficiencia Renal/inducido químicamente , Adulto , Anciano , Antivirales/uso terapéutico , Creatinina/sangre , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/etiología , Electrólitos/metabolismo , Femenino , Humanos , Hipocalcemia/patología , Hipopotasemia/patología , Magnesio/sangre , Masculino , Persona de Mediana Edad , Gravedad del Paciente , Estudios RetrospectivosRESUMEN
Photomultiplier tubes (PMTs) and silicon photomultipliers (SiPMs) have played essential roles in various applications, such as fundamental particle physics experiments, nuclear medicine, and environmental radiation monitoring, for several decades. Understandings their physical properties as well as present applications is indispensable for the development and future applications of these detectors. In this review, we describe the physical principles of PMTs and SiPMs and introduce various applications of these detectors.
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Monitoreo de Radiación , Diagnóstico por Imagen , Fotones , Física , RadiografíaRESUMEN
X-ray and gamma-ray photons are widely used for imaging but require a mathematical reconstruction step, known as tomography, to produce cross-sectional images from the measured data. Theoretically, the back-to-back annihilation photons produced by positron-electron annihilation can be directly localized in three-dimensional space using time-of-flight information without tomographic reconstruction. However, this has not yet been demonstrated due to the insufficient timing performance of available radiation detectors. Here, we develop techniques based on detecting prompt Cerenkov photons, which when combined with a convolutional neural network for timing estimation resulted in an average timing precision of 32 picoseconds, corresponding to a spatial precision of 4.8 mm. We show this is sufficient to produce cross-sectional images of a positron-emitting radionuclide directly from the detected coincident annihilation photons, without using any tomographic reconstruction algorithm. The reconstruction-free imaging demonstrated here directly localizes positron emission, and frees the design of an imaging system from the geometric and sampling constraints that normally present for tomographic reconstruction.
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The molecular and clinical characteristics of non-ampullary duodenal adenomas and intramucosal adenocarcinomas are not fully understood because they are rare. To clarify these characteristics, we performed genetic and epigenetic analysis of cancer-related genes in these lesions. One hundred and seven non-ampullary duodenal adenomas and intramucosal adenocarcinomas, including 100 small intestinal-type tumors (90 adenomas and 10 intramucosal adenocarcinomas) and 7 gastric-type tumors (2 pyloric gland adenomas and 5 intramucosal adenocarcinomas), were investigated. Using bisulfite pyrosequencing, we assessed the methylation status of CpG island methylator phenotype (CIMP) markers and MLH1. Then using next-generation sequencing, we performed targeted exome sequence analysis within 75 cancer-related genes in 102 lesions. There were significant differences in the clinicopathological and molecular variables between small intestinal- and gastric-type tumors, which suggests the presence of at least two separate carcinogenic pathways in non-ampullary duodenal adenocarcinomas. The prevalence of CIMP-positive lesions was higher in intramucosal adenocarcinomas than in adenomas. Thus, concurrent hypermethylation of multiple CpG islands is likely associated with development of non-ampullary duodenal intramucosal adenocarcinomas. Mutation analysis showed that APC was the most frequently mutated gene in these lesions (56/102; 55%), followed by KRAS (13/102; 13%), LRP1B (10/102; 10%), GNAS (8/102; 8%), ERBB3 (7/102; 7%), and RNF43 (6/102; 6%). Additionally, the high prevalence of diffuse or focal nuclear ß-catenin accumulation (87/102; 85%) as well as mutations of WNT pathway components (60/102; 59%) indicates the importance of WNT signaling to the initiation of duodenal adenomas. The higher than previously reported frequency of APC gene mutations in small bowel adenocarcinomas as well as the difference in the APC mutation distributions between small intestinal-type adenomas and intramucosal adenocarcinomas may indicate that the adenoma-carcinoma sequence has only limited involvement in duodenal carcinogenesis. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
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Adenocarcinoma/genética , Adenoma/genética , Biomarcadores de Tumor/genética , Neoplasias Duodenales/genética , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Mutación , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Adenoma/diagnóstico , Adenoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinogénesis/genética , Carcinogénesis/patología , Variaciones en el Número de Copia de ADN , Metilación de ADN , Neoplasias Duodenales/diagnóstico , Neoplasias Duodenales/patología , Duodeno/patología , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Mucosa Intestinal/patología , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: The relationship between serum creatinine and calcium (Ca) was investigated in hematopoietic stem cell transplantation (HSCT) patients treated with foscarnet. MATERIALS AND METHODS: A retrospective study was performed to investigate the development of foscarnet-induced renal dysfunction in patients who received HSCT from April 2010 to November 2018 at the Kindai University Nara Hospital. A total of 80 patients were identified from the medical records, and 42 patients who met the inclusion criteria were enrolled in this study. Renal dysfunction was classified according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. RESULTS: A significant inverse relationship was observed between serum creatinine and Ca levels (r = -0.372; p < 0.0001; y = -0.537x + 9.268). A separate analysis divided into renal dysfunction and non-renal dysfunction groups showed that there was a signiï¬cant relationship between serum creatinine and Ca levels in the renal dysfunction group (r = -0.531; p < 0.0001; y = -0.617x + 9.239) but not in the non-renal dysfunction group (r = -0.011; p = 0.561; y = -0.023x + 8.934). The optimal cutoff for the minimum Ca level was calculated to be 8.1 mg/mL. CONCLUSION: A significant inverse relationship was observed between serum creatinine and Ca levels in HSCT patients with foscarnet-induced renal dysfunction. Foscarnet-induced renal dysfunction should be noted if Ca levels fall below 8.1 mg/dL. Monitoring Ca levels may be useful for detecting renal dysfunction at early stages in patients treated with foscarnet.
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Calcio/sangre , Creatinina/sangre , Foscarnet/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Humanos , Estudios RetrospectivosRESUMEN
Recent studies have shown that colorectal serrated lesions, which include sessile serrated adenomas (SSAs) and traditional serrated adenomas (TSAs), are precursors of colorectal cancer. However, the molecular mechanisms underlying the carcinogenesis, particularly in TSAs, remain largely uncharacterized. To clarify their molecular and clinicopathological characteristics, we performed mutation and methylation analyses of cancer-associated genes in 78 serrated lesions, including TSAs, SSAs and microvesicular hyperplastic polyps. Target exon sequence analysis was performed with 39 genes, including genes known to be frequently mutated in colorectal cancers and/or serrated lesions. We also used bisulfite pyrosequencing to assess the methylation status of various cancer-associated genes and marker genes of the CpG island methylator phenotype (CIMP). The prevalence of mutations in genes associated with Wnt signaling was significantly higher in TSAs than SSAs (65% vs. 28%, p < 0.01). Among those, RNF43 mutations were observed in 38% of TSAs and 17% of SSAs. In immunohistochemical studies of 39 serrated lesions, the prevalence of abnormal nuclear ß-catenin accumulation was significantly higher in TSAs (57%) than SSAs (8%) (P = 0.01). SMOC1 methylation was detected in 54% of TSAs but in no SSAs (p < 0.01). Additionally, SMOC1 methylation was more prevalent among TSAs with KRAS mutation (82%) than with BRAF mutation (38%, p = 0.03). Lesions with CIMP-high or RNF43 mutations were detected only in TSAs with BRAF mutation, suggesting two distinct carcinogenic pathways in TSAs. Mutations in genes associated with Wnt signaling play a greater role in the carcinogenesis of TSAs than SSAs.