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CJH Kramer L Lanjouw D Ruano A ter Elst G Santandrea N Solleveld-Westerink N Werner AH van der Hout CD de Kroon T van Wezel LPV Berger M Jalving J Wesseling VTHBM Smit GH de Bock CJ van Asperen MJE Mourits MPG Vreeswijk J Bart T Bosse 《The Journal of pathology》2024,262(2):137-146
The identification of causal BRCA1/2 pathogenic variants (PVs) in epithelial ovarian carcinoma (EOC) aids the selection of patients for genetic counselling and treatment decision-making. Current recommendations therefore stress sequencing of all EOCs, regardless of histotype. Although it is recognised that BRCA1/2 PVs cluster in high-grade serous ovarian carcinomas (HGSOC), this view is largely unsubstantiated by detailed analysis. Here, we aimed to analyse the results of BRCA1/2 tumour sequencing in a centrally revised, consecutive, prospective series including all EOC histotypes. Sequencing of n = 946 EOCs revealed BRCA1/2 PVs in 125 samples (13%), only eight of which were found in non-HGSOC histotypes. Specifically, BRCA1/2 PVs were identified in high-grade endometrioid (3/20; 15%), low-grade endometrioid (1/40; 2.5%), low-grade serous (3/67; 4.5%), and clear cell (1/64; 1.6%) EOCs. No PVs were identified in any mucinous ovarian carcinomas tested. By re-evaluation and using loss of heterozygosity and homologous recombination deficiency analyses, we then assessed: (1) whether the eight ‘anomalous’ cases were potentially histologically misclassified and (2) whether the identified variants were likely causal in carcinogenesis. The first ‘anomalous’ non-HGSOC with a BRCA1/2 PV proved to be a misdiagnosed HGSOC. Next, germline BRCA2 variants, found in two p53-abnormal high-grade endometrioid tumours, showed substantial evidence supporting causality. One additional, likely causal variant, found in a p53-wildtype low-grade serous ovarian carcinoma, was of somatic origin. The remaining cases showed retention of the BRCA1/2 wildtype allele, suggestive of non-causal secondary passenger variants. We conclude that likely causal BRCA1/2 variants are present in high-grade endometrioid tumours but are absent from the other EOC histotypes tested. Although the findings require validation, these results seem to justify a transition from universal to histotype-directed sequencing. Furthermore, in-depth functional analysis of tumours harbouring BRCA1/2 variants combined with detailed revision of cancer histotypes can serve as a model in other BRCA1/2-related cancers. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. 相似文献
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Three children aged 17 months to 17 years developed right-sided peripheral lung abscesses. Clinical signs were fever and cough. Laboratory cultures were negative, and the patients did not respond to appropriate antibiotic coverage. Under fluoroscopic guidance, purulent material was removed from the abscesses by needle aspiration. The patients became afebrile within 24 hours; none suffered complications of bleeding or pneumothorax. Cultures of the aspirate were positive for microorganisms sensitive to the prescribed treatments. A simple aspiration technique is described and proposed as useful for selected patients when surgical drainage is recommended. There was no morbidity in our cases, and recovery from a typically prolonged course was shortened by the procedure. 相似文献
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功能性消化不良者胃排空功能和体表胃电变化的研究 总被引:1,自引:0,他引:1
以SPECT胃排空检测技术和WCDF-4B胃电分析仪检测了12例FD患者液、固体食物胃排空和体表胃电图的变化。结果显示:FD患者的液体胃排空与对照组无明显差异,仅在摄食后比对照组更多地分布于远端胃内:固体食物的排模式发生变化,表现为初始排空较快,继后的排空延缓,7例半排空时间延长。 相似文献
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Packed red cell units (n = 10) were filtered and divided equally. One-half unit from each donor was irradiated (x) (3500 cGy). On Days 0, 14, 28, and 42, ATP, K+, Na+, lactate dehydrogenase (LDH), plasma-free hemoglobin (PFH), and pH were determined. The reduction in ATP was greater in the irradiated than the nonirradiated (y) units by Day 42 (mean x-y: -70, p = 0.0005). The increase in K+ was greater in the irradiated than nonirradiated units on Days 14, 28, and 42 (mean x-y: 17-20, p = 0.0001). Decrease in pH and increases in LDH and PFH were significant (p less than 0.05) on Day 42 only. K+ increases added only 1.7 to 2.0 mmol per unit, a difference felt to be clinically insignificant. The changes noted in ATP, pH, LDH, and PFH are significant but minimal on Day 42 and imply that viability changes would also be minimal. These biochemical data support the storage of irradiated units for at least 28 days. 相似文献