Oral carcinoma: Clinical evaluation using diffusion kurtosis imaging and its correlation with histopathologic findings

PURPOSE: In this study, we aimed to determine the usefulness of diffusion kurtosis imaging (DKI) as a noninvasive method for evaluation of the histologic grade and lymph node metastasis in patients with oral carcinoma. MATERIALS AND METHODS: Twenty-seven patients with oral carcinoma were examined with a 3-T MR system and 16-channel coil. DKI data were obtained by a single-shot echo-planar imaging sequence with repetition time, 10,000ms; echo time, 94ms; field of view, 250x204.25ms; matrix, 120x98; section thickness, 4mm; four b values of 0, 500, 1000, and 2000s/mm(2); and motion-probing gradients in three orthogonal directions. Diffusivity (D) and kurtosis (K) were calculated using the equation: S=S0 exp(-b D+b(2) D(2) K/6). Conventional apparent diffusion coefficient (ADC) was also calculated. The MR images were compared with the histopathologic findings. RESULTS: Relative to the histologic grades (Grades 1, 2, and 3) of the 27 oral carcinomas, D values showed a significant inverse correlation (r=-0.885; P<0.001) and K values showed a significant positive correlation (r=0.869; P<0.001), whereas ADC values showed no significant correlation (r=-0.311; P=0.115). When comparing between metastatic and non-metastatic lymph nodes, significant differences in the D values (P<0.001) and K values (P<0.001), but not the ADC values (P=0.110) became apparent. CONCLUSIONS: In patients with oral carcinoma, DKI seems to be clinically useful for the evaluation of histologic grades and lymph node metastasis

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Predictive factors for a successful diagnostic bronchoscopy of ground-glass nodules

Introduction: Since the National Lung Screening Trial demonstrated the utility of low-dose computed tomography screening for lung cancer, the detection rate of ground-glass nodules (GGNs) has increased. Endobronchial ultrasound with a guide sheath (EBUS-GS) is widely performed to diagnose peripheral pulmonary lesions, but there are not enough reports on the predictive ability of EBUS-GS in diagnosing GGNs. The aim of this study is to investigate the predictive factors for a successful diagnostic bronchoscopy for GGNs. Methods: Consecutive patients who underwent diagnostic bronchoscopy for GGNs from September 2012 to January 2016 were enrolled in this study. From these, cases who underwent EBUS-GS were selected. They were reviewed and analyzed to examine the association between the diagnostic yield and the following clinical factors: lesion size, lobar position, location, consolidation-to-tumor ratio, visibility on X-ray, use of virtual bronchoscopy, bronchus sign, guide sheath size, and number of biopsies. Results: We enrolled 254 cases, of which 167 were diagnosed using EBUS-GS (65.7% diagnostic yield). Univariate analysis indicated that a positive bronchus sign was a significant factor for higher diagnostic yield (72.9% vs. 34.0%; P < 0.001). The use of virtual bronchoscopy also tended toward a higher yield, but the result was not significant (69.0% vs. 54.4%; P = 0.058). However, multivariate analysis indicated that both were significantly associated with higher diagnostic yield (P < 0.001, odds ratio [OR]: 5.35; P < 0.001, OR: 1.97, respectively). Conclusions: Our results suggest that a positive bronchus sign and the use of virtual bronchoscopy are positive predictive factors for successful diagnostic bronchoscopy of GGNs

Three-Dimensional Reconstruction of Oral Tongue Squamous Cell Carcinoma at Invasion Front

We conducted three-dimensional (3D) reconstruction of oral tongue squamous cell carcinoma (OTSCC) using serial histological sections to visualize the architecture of invasive tumors. Fourteen OTSCC cases were collected from archival paraffin-embedded specimens. Based on a pathodiagnostic survey of whole cancer lesions, a core tissue specimen (3 mm in diameter) was dissected out from the deep invasion front using a paraffin tissue microarray. Serial sections (4 μm thick) were double immunostained with pan-cytokeratin and Ki67 antibodies and digitized images were acquired using virtual microscopy. For 3D reconstruction, image registration and RGB color segmentation were automated using ImageJ software to avoid operator-dependent subjective errors. Based on the 3D tumor architecture, we classified the mode of invasion into four types: pushing and bulky architecture; trabecular architecture; diffuse spreading; and special forms. Direct visualization and quantitative assessment of the parenchymal-stromal border provide a new dimension in our understanding of OTSCC architecture. These 3D morphometric analyses also ascertained that cell invasion (individually and collectively) occurs at the deep invasive front of the OTSCC. These results demonstrate the advantages of histology-based 3D reconstruction for evaluating tumor architecture and its potential for a wide range of applications

Malignant lymphoma of the oral cavity : A single-center study of 28 cases

Objectives:This study aimed to determine the clinicopathological features, treatment methods and prognosis in patients with malignant lymphoma of the oral cavity.Methods:We retrospectively examined 28 cases of malignant lymphoma of the oral cavity based on the novel World Health Organization pathological classification.Results:The most common primary site was the upper gingival area (32.1%) and the most frequent initial symptom was painless swelling (48.5%); 7.1% of cases were stage III and 21.4% were stage IV according to the Ann Arbor classification. The most common histologic type was diffuse large B-cell lymphoma. Clinically, 14.3% of cases were classified as highly aggressive, and three-quarters of these cases were ulcerated. The most common type of chemotherapy was R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone), which was used in 28.6% of patients. Five-year overall survival was 69.7% for all cases and 53.5% for those with diffuse large B-cell lymphoma.Conclusions:Patients with an Ann Arbor disease classification of stage III or IV and histologically aggressive disease are not uncommon and have poor prognosis. Therefore, prompt biopsy is needed for painless swelling of the upper gingiva to perform differential diagnosis of malignant lymphoma of the oral cavity