Esophageal metastasis of renal cell carcinoma resected by endoscopic submucosal dissection: a case report

Background: Esophageal metastasis of renal cell carcinoma (RCC) is extremely rare. We have described herein a case of a 59-year-old man with esophageal metastasis of RCC that was endoscopically resected.Case presentation: The case was a 59-year-old man who had undergone left nephrectomy for renal clear cell carcinoma 17 years ago and splenectomy for splenic metastasis 3 years ago. Esophagogastroduodenoscopy (EGD) performed 9 years ago revealed a small reddish elevated lesion with a smooth surface in the middle esophagus; this lesion increased in size 4 years ago. However, no biopsy was performed. The lesion continued to grow in size and was found to have become nodular during the present observation. Biopsy revealed clear cell carcinoma. Endoscopic ultrasound (EUS) revealed that the lesion had not invaded the submucosa, and contrast-enhanced computed tomog-raphy did not reveal any other metastasis. The lesion was successfully removed en bloc via endoscopic submucosal dissection (ESD). Pathologically, the tumor was detected in the subepithelium with focal infiltration of the muscularis mucosa. It consisted of monotonous cells with small nuclei and a clear cytoplasm. Immunohistological findings indi-cated that the tumor was a metastasis of RCC. The lateral and vertical margins were noted to be free.Conclusions: We have presented herein a case of esophageal metastasis of RCC that had progressed over 9 years and was then resected en bloc through endoscopic submucosal dissection

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

高次精度MHDシミュレーションコードの開発とそれを用いた磁気回転不安定性が駆動する磁気乱流の研究

Tohoku University加藤雄人課

Identification of sphingoglycolipids in a patient regarded as having Fabry's disease.

Fabry's disease is one of the inherited diseases, in which sphingoglycolipids accumulate systemically in tissue as the result of defective α-galactosyl hydrolase. In this paper, we studied a 54 year-old female who had complaints of leg pain, palpebral edema and telangiectasis and in whom foam cells in renal biopsy as well as proteinuria in urinalysis were revealed. As an increase of sphingoglycolipids was discovered in her urinary sediment by biochemical analysis, this patient was shown to be suffering from Fabry's disease

En bloc kidney transplantation from pediatric donors to teenage recipients: Two case reports

Introduction Since the implementation of the new selection criteria in 2018, kidney donations from pediatric patients have been prioritized for pediatric recipients and kidney donations from pediatric donors have increased in Japan. Herein, we present two cases of en bloc kidney transplantation. Case presentation Case 1: A 19‐year‐old male patient who had been on hemodialysis for 5 years due to end‐stage renal disease. After brain death, a graft from a 5‐year‐old boy was transplanted into the right iliac fossa. Case 2: A 19‐year‐old male patient, who had previously undergone a living kidney transplantation at the age of 3, received a secondary cadaveric kidney transplantation in the left iliac fossa. The graft was procured from a 17‐month‐old girl following cardiac death. Conclusion This report will help surgeons perform en bloc kidney transplantation in the growing number of pediatric kidney donations, such as those in Japan

Presence of Cytokeratin 19-Expressing Cholangiocarcinoma-Like Tumour in a Liver Metastatic Lesion of Rectal Neuroendocrine Tumour

Introduction: Tumours with adenocarcinoma and neuroendocrine components have often been reported, although the reason underlying the dual components remains unclear. Case Presentation: A 43-year-old woman with multiple liver metastatic lesions of rectal neuroendocrine tumour underwent primary tumour resection and subsequent liver transplantation. Pathological examination indicated a cholangiocarcinoma-like tumour with gland formation, adjacent to a liver metastatic lesion of the neuroendocrine tumour. This tumour comprised atypical columnar epithelium, and stained positively for neuroendocrine markers and the ductal marker cytokeratin 19, indicating amphicrine properties and a partial cholangiocarcinoma phenotype – features not observed in the primary and metastatic neuroendocrine tumours. Conclusion: The presence of adenocarcinoma only at the metastatic site indicated that neuroendocrine tumour cells acquired stemness and differentiated into adenocarcinoma through metastasis, or that the adenocarcinoma newly arose from the adjacent epithelium influenced by the neuroendocrine tumour. We propose a novel mechanism for the pathogenesis of mixed tumours in neuroendocrine tumours

Early Experiences of One-Level Total Disc Replacement (Prestige LP) in Japan: A Comparison of Short-Term Outcomes with Anterior Cervical Discectomy with Fusion

Introduction: In Japan, cervical total disc replacement (TDR) was approved in 2017. However, because of its short history, no comparative study between cervical TDR and anterior cervical discectomy with fusion (ACDF) has been conducted in the country. Therefore, we examined and compared the surgical outcomes of TDR and ACDF for one-level cervical degenerative diseases. Methods: In total, 50 patients who had received anterior surgeries for one-level cervical degenerative diseases were investigated. Among them, 25 underwent TDR (Prestige LP; Medtronic), whereas the other 25 patients underwent ACDF. ACDF samples were selected from cases conducted before the approval of TDR (−2017.9) and were retrospectively judged to be indicated for TDR. Before and at 1 year after surgery, clinical and radiological outcomes were evaluated. Results: No significant differences in terms of patient demographics between the two groups were observed. A longer operative time was observed in the TDR group than in the ACDF group. Postoperatively, no differences in the Japanese Orthopaedic Association score for cervical myelopathy (C-JOA) score, neck pain visual analog scale, C2-7 angle, and C2-7 range of motion (ROM) were determined. TDR tended to show better neck disability index (NDI) scores postoperatively when compared with ACDF. The local angle at operative level was larger in ACDF. In TDR, the local ROMs were maintained postoperatively; however, in ACDF, the local ROM at the operative level was decreased, and the local ROMs at adjacent levels were increased postoperatively. In the TDR group, although heterotopic ossification was observed in 11 patients (44.0%), and anterior bone loss was identified in 14 patients (56.0%), these issues did not affect surgical outcomes. Conclusions: Conclusively, no differences in terms of C-JOA score and neck pain between patients treated through TDR and ACDF were observed. However, a trend of better NDI scores was identified with TDR. While TDR maintained postoperative ROMs, ACDF showed an increase in the local ROMs at adjacent levels