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Hai-Yang Chen Li-Li Feng Ming Li Huai-Qiang Ju Yi Ding Mei Lan Shu-Mei Song Wei-Dong Han Li Yu Ming-Biao Wei Xiao-Lin Pang Fang He Shuai Liu Jian Zheng Yan Ma Chu-Yang Lin Ping Lan Mei-Jin Huang Yi-Feng Zou Zu-Li Yang Ting Wang Jin-Yi Lang Guy R. Orangio Vitaliy Poylin Jaffer A Ajani Wei-Hu Wang Xiang-Bo Wan 《The oncologist》2021,26(5):e780-e793
BackgroundThe National Comprehensive Cancer Network''s Rectal Cancer Guideline Panel recommends American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) system to evaluate pathologic response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC). Yet, the clinical significance of the AJCC/CAP TRG system has not been fully defined.Materials and MethodsThis was a multicenter, retrospectively recruited, and prospectively maintained cohort study. Patients with LARC from one institution formed the discovery set, and cases from external independent institutions formed a validation set to verify the findings from discovery set. Overall survival (OS), disease‐free survival (DFS), local recurrence‐free survival (LRFS), and distant metastasis‐free survival (DMFS) were assessed by Kaplan‐Meier analysis, log‐rank test, and Cox regression model.ResultsThe discovery set (940 cases) found, and the validation set (2,156 cases) further confirmed, that inferior AJCC/CAP TRG categories were closely /ccorrelated with unfavorable survival (OS, DFS, LRFS, and DMFS) and higher risk of disease progression (death, accumulative relapse, local recurrence, and distant metastasis) (all p < .05). Significantly, pairwise comparison revealed that any two of four TRG categories had the distinguished survival and risk of disease progression. After propensity score matching, AJCC/CAP TRG0 category (pathological complete response) patients treated with or without adjuvant chemotherapy displayed similar survival of OS, DFS, LRFS, and DMFS (all p > .05). For AJCC/CAP TRG1–3 cases, adjuvant chemotherapy treatment significantly improved 3‐year OS (90.2% vs. 84.6%, p < .001). Multivariate analysis demonstrated the AJCC/CAP TRG system was an independent prognostic surrogate.ConclusionAJCC/CAP TRG system, an accurate prognostic surrogate, appears ideal for further strategizing adjuvant chemotherapy for LARC.Implications for PracticeThe National Comprehensive Cancer Network recommends the American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) four‐category system to evaluate the pathologic response to neoadjuvant treatment for patients with locally advanced rectal cancer; however, the clinical significance of the AJCC/CAP TRG system has not yet been clearly addressed. This study found, for the first time, that any two of four AJCC/CAP TRG categories had the distinguished long‐term survival outcome. Importantly, adjuvant chemotherapy may improve the 3‐year overall survival for AJCC/CAP TRG1–3 category patients but not for AJCC/CAP TRG0 category patients. Thus, AJCC/CAP TRG system, an accurate surrogate of long‐term survival outcome, is useful in guiding adjuvant chemotherapy management for rectal cancer. 相似文献
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Ronit Calderon-Margalit Oren Pleniceanu Dorit Tzur Michal Stern-Zimmer Arnon Afek Tomer Erlich Guy Verhovsky Lital Keinan-Boker Karl Skorecki Gilad Twig Asaf Vivante 《Journal of the American Society of Nephrology : JASN》2021,32(2):495
BackgroundIncreasing cancer incidence among children alongside improved treatments has resulted in a growing number of pediatric cancer survivors. Despite childhood cancer survivors’ exposure to various factors that compromise kidney function, few studies have investigated the association between childhood cancer and future kidney disease.MethodsTo assess the risk of ESKD among childhood cancer survivors, we conducted a nationwide, population-based, retrospective cohort study that encompassed all Israeli adolescents evaluated for mandatory military service from 1967 to 1997. After obtaining detailed histories, we divided the cohort into three groups: participants without a history of tumors, those with a history of a benign tumor (nonmalignant tumor with functional impairment), and those with a history of malignancy (excluding kidney cancer). This database was linked to the Israeli ESKD registry to identify incident ESKD cases. We used Cox proportional hazards models to estimate the hazard ratio (HR) of ESKD.ResultsOf the 1,468,600 participants in the cohort, 1,444,345 had no history of tumors, 23,282 had a history of a benign tumor, and 973 had a history of malignancy. During a mean follow-up of 30.3 years, 2416 (0.2%) participants without a history of tumors developed ESKD. Although a history of benign tumors was not associated with an increased ESKD risk, participants with a history of malignancy exhibited a substantially elevated risk for ESKD compared with participants lacking a history of tumors, after controlling for age, sex, enrollment period, and paternal origin (adjusted HR, 3.2; 95% confidence interval, 1.3 to 7.7).ConclusionsChildhood cancer is associated with an increased risk for ESKD, suggesting the need for tighter and longer nephrological follow-up. 相似文献
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Hamilton Erika Cortes Javier Ozyilkan Ozgur Chen Shin-Cheh Petrakova Katarina Manikhas Aleksey Jerusalem Guy Hegg Roberto Huober Jens Zhang Wei Chen Yanyun Martin Miguel 《Breast cancer research and treatment》2022,195(1):55-64
Breast Cancer Research and Treatment - Resistance to endocrine therapy poses a major clinical challenge for patients with hormone receptor-positive (HR?+), human epidermal growth factor... 相似文献
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<正>Alzheimer’s and Parkinson’s diseases are neurodegenerative disorders pathologically classified by the accumulation of amyloidogenic proteins into insoluble inclusions within the brain.Specifically,amyloid plaques in the brains of Alzheimer’s disease patients are comprised of amyloid-β(Aβ)peptide,the product of sequential cleavage of the amyloid precursor protein byβ-andγ-secretases.Similarly,α-synuclein 相似文献
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John T. Langfitt Mark Quigg Guofen Yan Wei Yu Mariann M. Ward Nicholas M. Barbaro Edward F. Chang Donna K. Broshek Kenneth D. Laxer Andrew J. Cole Penny K. Sneed Christopher Hess Manjari Tripathi Christiaanne N. Heck John W. Miller Paul A. Garcia Andrew McEvoy Nathan B. Fountain Vicenta Salanova Robert C. Knowlton Anto Bagi Thomas Henry Siddharth Kapoor Guy McKhann Adriana E. Palade Markus Reuber Evelyn Tecoma 《Epilepsia》2019,60(7):1453-1461
10.
Aakash Shetty Ziv Gan-Or Setareh Ashtiani Jennifer A. Ruskey Bart van de Warrenburg Tessa Wassenberg Erik-Jan Kamsteeg Guy A. Rouleau Oksana Suchowersky 《European journal of medical genetics》2019,62(12):103605
Aims and objectiveTo characterize the phenotype of CAPN1 (SPG76) mutations in patients diagnosed with hereditary spastic paraplegia (HSP).BackgroundThe CAPN1 gene, located on chromosome 11q13.1, is a protein-coding gene involved in neuronal plasticity, migration, microtubular regulation and cerebellar development. Several families with CAPN1 mutations have recently been reported to present with autosomal recessive (AR) HSP and/or ataxia.MethodPatients with HSP were identified through neurological and genetic clinics with detailed phenotyping. Whole exome sequencing revealed novel pathogenic CAPN1 mutations in four patients from 3 families.ResultsAffected families were of Turkish, Japanese, and Punjabi descent and all were consanguineous. Onset of spastic paraplegia in the four patients was between 20 and 37 years. Two also had mild ataxia. Three different novel, homozygous mutations in CAPN1 were found: c.2118+1G > T, c.397C > T, c.843+1G > C. The patient with the earliest onset also manifested profound muscle weakness, likely related to a second homozygous mutation in DYSF (dysferlinopathy).ConclusionsThe phenotype of AR CAPN1 mutations appears to be spastic paraplegia with or without ataxia; onset is most commonly in adulthood. Eye movement abnormalities, skeletal defects, peripheral neuropathy and amyotrophy can sometimes be seen. Occasionally, patients can present with ataxia, illustrating the genotypic and phenotypic overlap between HSP and spastic ataxia. With the advent of exome sequencing, mutations in more than one gene can be identified, which may contribute to the phenotypic variation, even within a family. 相似文献