scholarly journals Prognostic Value of the Diversity of Nuclear Chromatin Compartments in Gynaecological Carcinomas

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3838
Author(s):  
Andreas Kleppe ◽  
Fritz Albregtsen ◽  
Jone Trovik ◽  
Gunnar B. Kristensen ◽  
Håvard E. Danielsen

Statistical texture analysis of cancer cell nuclei stained for DNA has recently been used to develop a pan-cancer prognostic marker of chromatin heterogeneity. In this study, we instead analysed chromatin organisation by automatically quantifying the diversity of chromatin compartments in cancer cell nuclei. The aim was to investigate the prognostic value of such an assessment in relation to chromatin heterogeneity and as a potential supplement to pathological risk classifications in gynaecological carcinomas. The diversity was quantified by calculating the entropy of both chromatin compartment sizes and optical densities within compartments. We analysed a median of 281 nuclei (interquartile range (IQR), 273 to 289) from 246 ovarian carcinoma patients and a median of 997 nuclei (IQR, 502 to 1452) from 791 endometrial carcinoma patients. The prognostic value of the entropies and chromatin heterogeneity was moderately strongly correlated (r ranged from 0.68 to 0.73), but the novel marker was observed to provide additional prognostic information. In multivariable analysis with clinical and pathological markers, the hazard ratio associated with the novel marker was 2.1 (95% CI, 1.3 to 3.5) in ovarian carcinoma and 2.4 (95% CI, 1.5 to 3.9) in endometrial carcinoma. Integration with pathological risk classifications gave three risk groups with distinctly different prognoses. This suggests that the novel marker of diversity of chromatin compartments might possibly contribute to the selection of high-risk stage I ovarian carcinoma patients for adjuvant chemotherapy and low-risk endometrial carcinoma patients for less extensive surgery.

2020 ◽  
Vol 9 (12) ◽  
pp. 3882
Author(s):  
Thomas Stiermaier ◽  
Kira Busch ◽  
Torben Lange ◽  
Toni Pätz ◽  
Moritz Meusel ◽  
...  

Cardiac magnetic resonance (CMR)-derived left ventricular (LV) global longitudinal strain (GLS) provides incremental prognostic information on various cardiovascular diseases but has not yet been investigated comprehensively in patients with Takotsubo syndrome (TS). This study evaluated the prognostic value of feature tracking (FT) GLS, tissue tracking (TT) GLS, and fast manual long axis strain (LAS) in 147 patients with TS, who underwent CMR at a median of 2 days after admission. Long-term mortality was assessed 3 years after the acute event. In contrast to LV ejection fraction and tissue characteristics, impaired FT-GLS, TT-GLS and fast manual LAS were associated with adverse outcome. The best cutoff points for the prediction of long-term mortality were similar with all three approaches: FT-GLS −11.28%, TT-GLS −11.45%, and fast manual LAS −10.86%. Long-term mortality rates were significantly higher in patients with FT-GLS > −11.28% (25.0% versus 9.8%; p = 0.029), TT-GLS > −11.45% (20.0% versus 5.4%; p = 0.016), and LAS > −10.86% (23.3% versus 6.6%; p = 0.014). However, in multivariable analysis, diabetes mellitus (p = 0.001), atrial fibrillation (p = 0.001), malignancy (p = 0.006), and physical triggers (p = 0.006) outperformed measures of myocardial strain and emerged as the strongest, independent predictors of long-term mortality in TS. In conclusion, CMR-based longitudinal strain provides valuable prognostic information in patients with TS, regardless of the utilized technique of assessment. Long-term mortality, however, is mainly determined by comorbidities.


2011 ◽  
Vol 29 (4) ◽  
pp. 392-397 ◽  
Author(s):  
Naseema Gangat ◽  
Domenica Caramazza ◽  
Rakhee Vaidya ◽  
Geeta George ◽  
Kebede Begna ◽  
...  

Purpose The Dynamic International Prognostic Scoring System (DIPSS) for primary myelofibrosis (PMF) uses five risk factors to predict survival: age older than 65 years, hemoglobin lower than 10 g/dL, leukocytes higher than 25 × 109/L, circulating blasts ≥ 1%, and constitutional symptoms. The main objective of this study was to refine DIPSS by incorporating prognostic information from karyotype, platelet count, and transfusion status. Patients and Methods Mayo Clinic databases for PMF were used to identify patients with available bone marrow histologic and cytogenetic information. Results Seven hundred ninety-three consecutive patients were selected and divided into two groups based on whether or not their referral occurred within (n = 428; training set) or after (n = 365; test set) 1 year of diagnosis. Multivariable analysis identified DIPSS, unfavorable karyotype, platelets lower than 100 × 109/L, and transfusion need as independent predictors of inferior survival. Hazard ratio (HR) –weighted adverse points were assigned to these variables to develop a composite prognostic model using the training set. The model was subsequently validated in the test set, and its application to all 793 patients resulted in median survivals of 185, 78, 35, and 16 months for low, intermediate-1 (HR, 2.2; 95% CI, 1.4 to 3.6), intermediate-2 (HR, 4.9; 95% CI, 3.2 to 7.7), and high-risk groups (HR, 10.7; 95% CI, 6.8 to 16.9), respectively (P < .001). Leukemia-free survival was predicted by the presence of thrombocytopenia or unfavorable karyotype (10-year risk of 31% v 12%; HR, 3.3; 95% CI, 1.9 to 5.6). Conclusion DIPSS plus effectively combines prognostic information from DIPSS, karyotype, platelet count, and transfusion status to predict overall survival in PMF. In addition, unfavorable karyotype or thrombocytopenia predicts inferior leukemia-free survival.


1995 ◽  
Vol 86 (11) ◽  
pp. 1049-1053 ◽  
Author(s):  
Hitoshi Tsuda ◽  
Kumiko Jiko ◽  
Shoichiro Tsugane ◽  
Masazumi Yajima ◽  
Takuro Yamada ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2874
Author(s):  
Ludovic Gabellier ◽  
Caroline Bret ◽  
Guillaume Bossis ◽  
Guillaume Cartron ◽  
Jérôme Moreaux

Cytogenetically normal acute myeloid leukemias (CN-AML) represent about 50% of total adult AML. Despite the well-known prognosis role of gene mutations such as NPM1 mutations of FLT3 internal tandem duplication (FLT3-ITD), clinical outcomes remain heterogeneous in this subset of AML. Given the role of genomic instability in leukemogenesis, expression analysis of DNA repair genes might be relevant to sharpen prognosis evaluation in CN-AML. A publicly available gene expression profile dataset from two independent cohorts of patients with CN-AML were analyzed (GSE12417). We investigated the prognostic value of 175 genes involved in DNA repair. Among these genes, 23 were associated with a prognostic value. The prognostic information provided by these genes was summed in a DNA repair score, allowing to define a group of patients (n = 87; 53.7%) with poor median overall survival (OS) of 233 days (95% CI: 184–260). These results were confirmed in two validation cohorts. In multivariate Cox analysis, the DNA repair score, NPM1, and FLT3-ITD mutational status remained independent prognosis factors in CN-AML. Combining these parameters allowed the identification of three risk groups with different clinical outcomes in both training and validation cohorts. Combined with NPM1 and FLT3 mutational status, our GE-based DNA repair score might be used as a biomarker to predict outcomes for patients with CN-AML. DNA repair score has the potential to identify CN-AML patients whose tumor cells are dependent on specific DNA repair pathways to design new therapeutic avenues.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4092-4092
Author(s):  
V. Formica ◽  
A. R. Norman ◽  
D. Cunningham ◽  
A. Wotherspoon ◽  
B. Sirohi ◽  
...  

4092 Background: The aim of this study was to assess the prognostic value of the revised neuroendocrine tumour (NET) WHO classification (2000) and to identify additional prognostic factors. Methods: 119 pts with metastatic NET arising from the GEP tract treated at the RMH were eligible for this retrospective study. All were classified according to WHO guidelines into well-differentiated and poorly-differentiated neuroendocrine carcinomas (WDNEC and PDNEC). Demographic, clinical and biochemical data at diagnosis were recorded as potential prognostic factors. The hazard ratios (HRs) between subgroups of patients were estimated by Cox regression analysis; survival curves were generated by Kaplan-Meier method. Approval for the study was obtained from the local ethics committee. Results: 8% of pts had PDNECs, 92% had WDNECs. Histological differentiation had the most impact on overall survival (OS) (HR = 4.02, 95%CI 1.26–12.82, p = 0.02, using WDNECs as the reference). In a WDNEC-restricted multivariate analysis, significantly abnormal LFTs and elevated u5HIAA were independent prognostic factors for survival (HR = 2.65, 95% CI 1.33–5.30, p = 0.006 and HR = 2.51, 95% CI 1.35–4.63, p = 0.003, respectively). Radiological evidence of liver metastases was not predictive of survival. These variables were used to create a WDNEC-specific prognostic model (low-risk = both normal, intermediate-risk = one abnormal, high-risk = both abnormal) (see table ). Statistically distinct median OS (mOS) were identified for each of the 3 risk groups. High-risk WDNECs had similar poor survival to PDNECs. Conclusion: This analysis supports the prognostic value of the WHO classification for metastatic NETs arising from the GEP tract. Risk stratification using readily available u5HIAA and LFTs may give additional prognostic information for WDNECs, although these observations need to be confirmed in an independent dataset. [Table: see text] No significant financial relationships to disclose.


2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 41-41
Author(s):  
Maria Christina Svensson ◽  
Jonna Berntsson ◽  
Charlotta Hedner ◽  
David Borg ◽  
Bjorn Nodin ◽  
...  

41 Background: Several studies have demonstrated a beneficial prognostic impact of tumour-infiltrating lymphocytes (TILs) in oesophageal and gastric adenocarcinoma, but whether this association differs according to adjuvant chemotherapy has not been reported. Herein, we examined the prognostic impact of different TIL subsets according to adjuvant chemotherapy in these cancer types. Methods: Immunohistochemistry was applied to assess the density of T cells (CD3+, CD8+, FoxP3+) and natural killer (NK)/T cells (CD56+) in radiochemonaïve tumors from a consecutive cohort of 174 patients with resected oesophageal or gastric adenocarcinoma. Cox proportional hazard’s modelling was applied to examine the impact of the investigated markers on time to recurrence (TTR) and overall survival (OS). Results: Dense infiltration of CD3+, CD8+, and FoxP3+ cells were all associated with a significantly prolonged TTR in univariable Cox regression analysis (hazard ratio[HR] = 0.57; 95% confidence interval [CI] 0.37-0.89; HR = 0.31, 95% CI 0.13-0.77, and HR = 0.44, 95% CI 0.28-0.68). This association remained significant for CD8+ and FoxP3+ cells in multivariable analysis, adjusted for age, tumour location, TNM stage, differentiation grade, resection margin and adjuvant chemotherapy ( HR = 0.30, 95% CI 0.11-0.77, and HR = 0.52, 95% CI 0.32-0.84), and borderline significant for CD3+ cells (HR = 0.63, 95% CI 0.39-1.02). Similar associations were observed for all markers in relation to OS. Notably, analysis in strata according to adjuvant chemotherapy revealed that none of the investigated lymphocyte subsets carried prognostic information in patients having received treatment (n = 13; 7.5%), with a significant treatment interaction between CD3+ and CD8+ cells and adjuvant chemotherapy (pinteraction0.035 and 0.021). Conclusions: These results confirm the prognostic value of a high density of TILs in gastroesophageal adenocarcinoma, but also indicate that adjuvant chemotherapy is only beneficial in patients with tumors displaying a low density of TILs. These results are of potential clinical relevance and need to be confirmed in additional, preferentially randomized, studies.


2016 ◽  
Vol 38 (1) ◽  
pp. 45-48
Author(s):  
A N Grabovoy ◽  
O O Kolesnik ◽  
T M Savchyn ◽  
S A Antoniuk

The aim: The creation of a mathematical model of survival in patients with colon adenocarcinoma based on multivariable analysis of the state of cancer cell nuclear apparatus. Patients and Methods: The study was performed on 141 samples of biopsy materials or material obtained during surgical treatment of the patients with colon adenocarcinoma or benign colon neoplasms with the use of histological, morphometric, densitometric, immunohistochemical and mathematical methods. Results: It has been shown that each discrete pattern of the state of adenocarcinoma cell nuclei (quantity of DNA, the number and volume of nuclear organizer regions, expression rates of Ki-67, Bcl-2 and p53) is prognostically invalid in the case of its separate use. Combination of these characteristics significantly enhances prognostic validity of the survival model. Based on equation of Cox proportional hazards, survival model of good quality for the patients with moderately and poorly differentiated adenocarcinoma and increased average DNA content in tumor cell nuclei has been created. Conclusion: The proposed survival model for colon adenocarcinoma demonstrates the quality twice superior to the model based on the use of tumor grade only (G) which in fact is presently used as a sole common independent histological criterion of prognosis.


2020 ◽  
Vol 11 (SPL1) ◽  
pp. 1198-1201
Author(s):  
Syed Yasir Afaque

In December 2019, a unique coronavirus infection, SARS-CoV-2, was first identified in the province of Wuhan in China. Since then, it spread rapidly all over the world and has been responsible for a large number of morbidity and mortality among humans. According to a latest study, Diabetes mellitus, heart diseases, Hypertension etc. are being considered important risk factors for the development of this infection and is also associated with unfavorable outcomes in these patients. There is little evidence concerning the trail back of these patients possibly because of a small number of participants and people who experienced primary composite outcomes (such as admission in the ICU, usage of machine-driven ventilation or even fatality of these patients). Until now, there are no academic findings that have proven independent prognostic value of diabetes on death in the novel Coronavirus patients. However, there are several conjectures linking Diabetes with the impact as well as progression of COVID-19 in these patients. The aim of this review is to acknowledge about the association amongst Diabetes and the novel Coronavirus and the result of the infection in such patients.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ying-Wen Lin ◽  
Mei Jiang ◽  
Xue-biao Wei ◽  
Jie-leng Huang ◽  
Zedazhong Su ◽  
...  

Abstract Background Increased D-dimer levels have been shown to correlate with adverse outcomes in various clinical conditions. However, few studies with a large sample size have been performed thus far to evaluate the prognostic value of D-dimer in patients with infective endocarditis (IE). Methods 613 patients with IE were included in the study and categorized into two groups according to the cut-off of D-dimer determined by receiver operating characteristic (ROC) curve analysis for in-hospital death: > 3.5 mg/L (n = 89) and ≤ 3.5 mg/L (n = 524). Multivariable regression analysis was used to determine the association of D-dimer with in-hospital adverse events and six-month death. Results In-hospital death (22.5% vs. 7.3%), embolism (33.7% vs 18.2%), and stroke (29.2% vs 15.8%) were significantly higher in patients with D-dimer > 3.5 mg/L than in those with D-dimer ≤ 3.5 mg/L. Multivariable analysis showed that D-dimer was an independent risk factor for in-hospital adverse events (odds ratio = 1.11, 95% CI 1.03–1.19, P = 0.005). In addition, the Kaplan–Meier curve showed that the cumulative 6-month mortality was significantly higher in patients with D-dimer > 3.5 mg/L than in those with D-dimer ≤ 3.5 mg/L (log-rank test = 39.19, P < 0.0001). Multivariable Cox regression analysis showed that D-dimer remained a significant predictor for six-month death (HR 1.11, 95% CI 1.05–1.18, P < 0.001). Conclusions D-dimer is a reliable prognostic biomarker that independently associated with in-hospital adverse events and six-month mortality in patients with IE.


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