Colorectal cancer lung metastasis: Could multidisciplinary management suggest the right strategy?

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15039-e15039
Author(s):  
Ina Valeria Zurlo ◽  
Michele Basso ◽  
Maria Teresa Congedo ◽  
Maria Letizia Vita ◽  
Leonardo Petracca Ciavarella ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Multivariate Analysis ◽  
Lung Metastasis ◽  
Rank Test ◽  
P Value ◽  
Multidisciplinary Management ◽  
Ras Status ◽  
The Right ◽  
The Impact

e15039 Background: Unlike liver metastases surgery, the resection of colorectal cancer lung metastasis (CCLM) is not standardized and data are still poor. Therefore, we conducted a retrospective analysis to evaluate the management of CCLM at our Centre. Methods: We retrospectively analyzed patients (pts) with CCLM treated at our Institution from Jan-2007 to Jan-2017. Aim of the study was to evaluate the impact of clinical and pathological features with survival outcomes (DFS and OS). Differences were compared with the use of log-rank test and parameters considered statistically significant ( p value < 0.5) at univariate were compared at multivariate analysis. Results: 141 pts were included in the analysis. 87 pts received a preoperative chemotherapy (pCT) and 54 an adjuvant (a)CT. In the whole population median DFS (mDFS) was 24 m (20-24) and median OS (mOS) 54 m (46-82), while 21 m (20-34) and 65 m (45-108) for pts undergoing pCT and 15 m (20-28) and 53 m (38 – 76) for those receiving aCT respectively, without statistically significant differences (p=0.4). Age, gender, PS, disease-free interval (DFI) (> or <24 months), primary tumor sidedness, mucinous histology, grading, RAS status, timing of lung metastasis (metachronous vs synchronous), number of lesions (>2), metastasis location (uni vs bilateral) and liver resection were evaluated at univariate and multivariate analysis. DFS was correlated with DFI > 24m (p=0.02), timing (p=0.03), number (p<0,0001) of metastasis and metastasis location (p=0.01) whereas OS was associated to DFI (p=0.02), number (p=0.0005), metastasis location (p=0.037) and RAS status (p=0.05) at univariate. At multivariate analysis, number of lesions correlated to DFS (p=0.0006) while DFI (p=0.0034) and RAS status (p=0.05) to OS. Conclusions: Our single Centre retrospective experience suggests an important clinical impact from surgery of CCLM based on mOS of the whole population. These data strengthen the role of a multidisciplinary management to allow pts to achieve surgery whenever possible, regardless of previous liver surgery, metachronous vs synchronous metastasis, DFI and RAS status.

scholarly journals Antioxidants Promote Intestinal Tumor Progression in Mice

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 241
Author(s):  
Zhiyuan V. Zou ◽  
Kristell Le Gal ◽  
Ahmed E. El Zowalaty ◽  
Lara E. Pehlivanoglu ◽  
Viktor Garellick ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Tumor Progression ◽  
Human Subjects ◽  
Plasma Concentrations ◽  
Intestinal Tumor ◽  
Adenomatous Polyposis ◽  
Intestinal Tumors ◽  
The Impact

Dietary antioxidants and supplements are widely used to protect against cancer, even though it is now clear that antioxidants can promote tumor progression by helping cancer cells to overcome barriers of oxidative stress. Although recent studies have, in great detail, explored the role of antioxidants in lung and skin tumors driven by RAS and RAF mutations, little is known about the impact of antioxidant supplementation on other cancers, including Wnt-driven tumors originating from the gut. Here, we show that supplementation with the antioxidants N-acetylcysteine (NAC) and vitamin E promotes intestinal tumor progression in the ApcMin mouse model for familial adenomatous polyposis, a hereditary form of colorectal cancer, driven by Wnt signaling. Both antioxidants increased tumor size in early neoplasias and tumor grades in more advanced lesions without any impact on tumor initiation. Importantly, NAC treatment accelerated tumor progression at plasma concentrations comparable to those obtained in human subjects after prescription doses of the drug. These results demonstrate that antioxidants play an important role in the progression of intestinal tumors, which may have implications for patients with or predisposed to colorectal cancer.

scholarly journals IL15RA and SMAD3 Genetic Variants Predict Overall Survival in Metastatic Colorectal Cancer Patients Treated with FOLFIRI Therapy: A New Paradigm

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1705
Author(s):  
Elena De Mattia ◽  
Jerry Polesel ◽  
Rossana Roncato ◽  
Adrien Labriet ◽  
Alessia Bignucolo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Prognostic Score ◽  
Chemotherapeutic Agents ◽  
Rank Test ◽  
P Value ◽  
Genetic Determinants ◽  
New Paradigm

A new paradigm in cancer chemotherapy derives from the interaction between chemotherapeutics, including irinotecan and 5-fluorouracil (5-FU), and the immune system. The patient’s immune response can modulate chemotherapy effectiveness, and, on the other hand, chemotherapeutic agents can foster tumor cell immunogenicity. On these grounds, the analysis of the cancer patients’ immunogenetic characteristics and their effect on survival after chemotherapy represent a new frontier. This study aims to identify genetic determinants in the immuno-related pathways predictive of overall survival (OS) after FOLFIRI (irinotecan, 5-FU, leucovorin) therapy. Two independent cohorts comprising a total of 335 patients with metastatic colorectal cancer (mCRC) homogeneously treated with first-line FOLFIRI were included in the study. The prognostic effect of 192 tagging genetic polymorphisms in 34 immune-related genes was evaluated using the bead array technology. The IL15RA rs7910212-C allele was associated with worse OS in both discovery (HR: 1.57, p = 0.0327, Bootstrap p-value = 0.0280) and replication (HR:1.71, p = 0.0411) cohorts. Conversely, SMAD3 rs7179840-C allele was associated with better OS in both discovery (HR:0.65, p = 0.0202, Bootstrap p-value = 0.0203) and replication (HR:0.61, p = 0.0216) cohorts. A genetic prognostic score was generated integrating IL15RA-rs7910212 and SMAD3-rs7179840 markers with inflammation-related prognostic polymorphisms we previously identified in the same study population (i.e., PXR [NR1I2]-rs1054190, VDR-rs7299460). The calculated genetic score successfully discriminated patients with different survival probabilities (p < 0.0001 log-rank test). These findings provide new insight on the prognostic value of genetic determinants, such as IL15RA and SMAD3 markers, and could offer a new decision tool to improve the clinical management of patients with mCRC receiving FOLFIRI.

scholarly journals Correlation of Body Mass Index with Oncologic Outcomes in Colorectal Cancer Patients: A Large Population-Based Study

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3592
Author(s):  
Chong-Chi Chiu ◽  
Chung-Han Ho ◽  
Chao-Ming Hung ◽  
Chien-Ming Chao ◽  
Chih-Cheng Lai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Body Mass Index ◽  
Body Weight ◽  
Body Mass ◽  
Survival Rates ◽  
Normal Weight ◽  
P Value ◽  
Administrative Claims ◽  
The Impact

It has been acknowledged that excess body weight increases the risk of colorectal cancer (CRC); however, there is little evidence on the impact of body mass index (BMI) on CRC patients’ long-term oncologic results in Asian populations. We studied the influence of BMI on overall survival (OS), disease-free survival (DFS), and CRC-specific survival rates in CRC patients from the administrative claims datasets of Taiwan using the Kaplan–Meier survival curves and the log-rank test to estimate the statistical differences among BMI groups. Underweight patients (<18.50 kg/m2) presented higher mortality (56.40%) and recurrence (5.34%) rates. Besides this, they had worse OS (aHR:1.61; 95% CI: 1.53–1.70; p-value: < 0.0001) and CRC-specific survival (aHR:1.52; 95% CI: 1.43–1.62; p-value: < 0.0001) rates compared with those of normal weight patients (18.50–24.99 kg/m2). On the contrary, CRC patients belonging to the overweight (25.00–29.99 kg/m2), class I obesity (30.00–34.99 kg/m2), and class II obesity (≥35.00 kg/m2) categories had better OS, DFS, and CRC-specific survival rates in the analysis than the patients in the normal weight category. Overweight patients consistently had the lowest mortality rate after a CRC diagnosis. The associations with being underweight may reflect a reverse causation. CRC patients should maintain a long-term healthy body weight.

The Perception of Russia in Europe in Context of Ukrainian Crisis

2015 ◽  
pp. 24-34
Author(s):  
N. Lapina
Keyword(s):  
Foreign Policy ◽  
Political Elites ◽  
Political Forces ◽  
Fruitful Cooperation ◽  
European Business ◽  
The Russian Federation ◽  
Ukrainian Crisis ◽  
The Right ◽  
The Impact

This article deals with the impact of various factors on the perception of Russia in different European countries. The focus is on the role of mass media, expert and political elites in forming of Russia's image, especially in the context of Ukrainian crisis. In this article, the reaction of different European counties to events in Ukraine, the polarization of European space is analyzed: some countries prefer to put a pressure on the Russian Federation, other – to find a way out of the critical situation and reach a compromise. Some political establishment representatives in France, Germany, Czech Republic support Russia and the reunification with Crimea, dispute sanctions against Russia. For such politicians, this support results from anti-American views and independent foreign policy aspirations. Other representatives of the European elite demand tougher approach and more pressure on Russia by any means whatsoever (including military ones). European business-communities reveal great interest in solving issues related to sanctions. Many entrepreneurs in Europe (in particular major corporations in France, UK, Germany, Italy), who profit from long and fruitful cooperation with Russia, are against anti-Russian sanctions. In view of the Ukrainian crisis, Russia has to face and solve various important issues. How can Russia implement a modernization project after burning all traditional bridges to the West and western friends and partners? What is the right way for Russian foreign policy to support and defend Russian-speaking people all over the world? Which European political forces can provide support to Russia? How can civil society affect and influence cooperation between Russia and Europe?

scholarly journals The Child's Right to Basic Education in Nigeria: A Commentary on the Decision in SERAP v. Nigeria

2018 ◽  
Vol 26 (4) ◽  
pp. 639-648 ◽  
Author(s):  
Aisosa Jennifer Isokpan ◽  
Ebenezer Durojaye
Keyword(s):  
Basic Education ◽  
Case Note ◽  
Third Parties ◽  
Government Officials ◽  
Right To Education ◽  
The Right ◽  
The Impact

This case note focuses on the justiciability as well as the impact of corruption on the realisation of the right to basic education. Through an assessment of the decision of the ECOWAS Court in SERAP v. Nigeria, it emphasises the role of states in ensuring that corrupt activities of government officials or third parties do not affect the enjoyment of the right. It equally emphasises the role of the Nigerian courts in ensuring a justiciable right to education.

scholarly journals Hubungan Beban Kerja Perawat Dengan Peran Perawat Anak Dalam Pendampingan Terapi Bermain

JKEP ◽  
2019 ◽  
Vol 4 (2) ◽  
pp. 104-113
Author(s):  
Ririn Nur Indah sari ◽  
Sari Windyastuti ◽  
Tri Sakti Widyaningsih
Keyword(s):  
Play Therapy ◽  
Sampling Technique ◽  
Rank Test ◽  
P Value ◽  
Test Statistic ◽  
Cross Sectional ◽  
Test Analysis ◽  
Spearman Rank ◽  
Nurse Workload

Nurse workload is very influential on child play therapy assistance caused by workload excessive workload, lack of facilities and infrastructure, nothing schedule for play therapy and the number of nurses  only 18 nurses, According to theory Gilles with the number of beds 34 needed 29 nurses. The purpose of this research is to know the Relationship of Nurse Workload with The Role of Child’s Nurse in Mentoring Play Therapy in Room Dahlia RSUD Dr. H Sewondo Kendal. This type of research is descriptive correlation with cross sectional. The sampling technique with total sampling, a sample is 18 respondents. Retrieval data using questionnaires and then tested into Spearman Rank test statistic. Based on research found 10 respondents (55,6%) have hard workload and 8 respondents (44,4%) have a light workload. The role of nurses in good categories 5 respondents (27,8%) and categories less is 13 respondents (72,2%). From result of Spearman Rank test analysis, get result of coefficient correlation value -868 in category very strong and obtained p value = 0,000 < 0,05 it’s mean Ha accepted and H0 rejected. There is a relantionship between the nurses workload with the role of child nurses in mentoring play therapy.

scholarly journals The impact of functional excess of footwear on the foot shape of 7-year-old girls and boys

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11277
Author(s):  
Ewa Puszczalowska-Lizis ◽  
Aleksandra Lukasiewicz ◽  
Sabina Lizis ◽  
Jaroslaw Omorczyk
Keyword(s):  
Regression Analysis ◽  
Hallux Valgus ◽  
Metatarsophalangeal Joint ◽  
Rank Test ◽  
Chi Square ◽  
First Metatarsophalangeal Joint ◽  
Longitudinal Arch ◽  
Transverse Arch ◽  
The Right ◽  
The Impact

Background Properly fitted shoes can support the development of growing feet and prevent problems and pathologies, not only in childhood, but also in adulthood. This points to the need to conduct research on the impact of shoe fitting on the structure of the foot in order to raise awareness and importance of this problem, to enable proper decisions regarding the purchase and use of shoes. The aim of this study was to analyze indoor footwear fit and its impact on foot structure in 7-year-old schoolchildren. Methods The CQ-ST podoscope and the Clevermess device were used for measurements. The analysis was carried out using the Mann Whitney U test, Wilcoxon signed-rank test, Chi-square test, regression analysis. Results About 40% of girls and boys had shoes that were incorrectly fitted in length, while as many as 74% of girls and 66% of boys wore shoes that were incorrectly fitted in width. Regression analysis demonstrated a statistically significant influence of the footwear length on longitudinal arch of the right and left foot and the transverse arch of the right foot. In boys, the length of the shoes shows associations with the right and left hallux valgus angle. Conclusion A significant percentage of the studied 7-year-olds, regardless of gender, wears inappropriately fitted shoes. In both sexes, the length of the footwear influenced the longitudinal arch of the right and left foot and the transverse arch of the right foot. Due to the deformity of the first metatarsophalangeal joint, the boys with hallux valgus require footwear which is wider and therefore their shoes need to be bigger in size.

Molecular profiling of advanced pancreatic ductal adenocarcinoma (PDAC): Role of ctDNA.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 425-425
Author(s):  
Angela Lamarca ◽  
Mairead Geraldine McNamara ◽  
Richard Hubner ◽  
Juan W. Valle
Keyword(s):  
Palliative Therapy ◽  
Progression Free Survival ◽  
Patient Characteristics ◽  
Molecular Profiling ◽  
Ductal Adenocarcinoma ◽  
P Value ◽  
Ctdna Analysis ◽  
Chemotherapy Initiation ◽  
The Impact

425 Background: Molecular profiling of tumour samples and circulating tumour DNA (ctDNA) may inform treatment of advanced cancer; the role of ctDNA to predict progression-free-survival (PFS) and overall survival (OS) in advanced PDAC is not fully understood. Methods: Eligible patients: those diagnosed with advanced PDAC undergoing molecular profiling [tumour (Foundation Medicine CDx/Caris) or ctDNA (FoundationMedicine Liquid (72 cancer-related genes))]. Baseline patient characteristics and molecular profiling outcomes, including mutant allele frequency (MAF) for pathological alterations were extracted. The primary aim was to assess the impact of presence of ctDNA at time of systemic chemotherapy initiation on PFS and OS. Results: Total of 26 samples (ctDNA 18 samples and 8 tumour samples) from 25 patients diagnosed with advanced PDAC underwent molecular profiling. When the whole population was analysed, the rate of sample analysis failure seemed to be higher when tumour tissue was tested (37.5%) compared to ctDNA (5.56%); p-value 0.072. The overall rate of identification of pathological findings was 72.73%, with 18.18% of patients having targetable findings [EGFRmut (1 patient), KRAS G12C mut (1 patient), FGFR2 fusion (1 patient), RNF43 mut (1 patient)]; these findings impacted treatment management in one patient only (RNF43 mutation; Wnt inhibitor). Variants of unknown significance were identified in 63.64% of samples. Patients with ctDNA analysis at time of palliative chemotherapy initiation (16 samples; 15 patients) were analysed [6 female (40.00%), median age 69.57 years (range 51.61-81.49), metastatic disease (66.67%), 80% first-line (80%), 20% second-line]. Pathological mutations were identified in 9/15 (60.00%) of these patients (KRAS mutation identified in 6/9). After median follow-up of 8.33 months from sample acquisition, 80% and 53.33% of patients had progressed and died, respectively. Median estimated PFS and OS were 5.65 months (95% CI 1.59-8.17) and 7.80 months (95% CI 4.13-not reached). Presence (vs absence) of pathological alterations in ctDNA showed a trend towards shorter PFS (2.91 vs 6.51 months; HR 1.38 (95% CI 0.40-4.77)) and OS (6.12 vs 9.72 months; HR 2.03 (95% CI 0.60-6.82)). Conclusions: This pilot study demonstrates the feasibility of ctDNA analysis in patients with advanced PDAC prior to initiation of palliative therapy. The presence of pathological alterations in ctDNA may prognosticate for worse PFS and OS. Larger studies are required to confirm these findings.

Stage-differentiated modelling of DNA methylation landscapes uncovers salient biomarkers and prognostic signatures in colorectal cancer progression

2021 ◽  
Author(s):  
Sangeetha Muthamilselvan ◽  
Abirami Raghavendran ◽  
Ashok Palaniappan
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Cpg Island ◽  
Early Stage ◽  
P Value ◽  
Consensus Analysis ◽  
One Stage ◽  
Differentially Methylated Genes ◽  
Methylation Patterns ◽  
The Impact

Abstract Background: Aberrant DNA methylation acts epigenetically to skew the gene transcription rate up or down, with causative roles in the etiology of cancers. However research on the role of DNA methylation in driving the progression of cancers is limited. In this study, we have developed a comprehensive computational framework for the stage-differentiated modelling of DNA methylation landscapes in colorectal cancer (CRC), and unravelled significant stagewise signposts of CRC progression. Methods: The methylation β - matrix was derived from the public-domain TCGA data, converted into M-value matrix, annotated with AJCC stages, and analysed for stage-salient genes using multiple approaches involving stage-differentiated linear modelling of methylation patterns and/or expression patterns. Differentially methylated genes (DMGs) were identified using a contrast against controls (adjusted p-value <0.001 and |log fold-change of M-value| >2). These results were filtered using a series of all possible pairwise stage contrasts (p-value <0.05) to obtain stage-salient DMGs. These were then subjected to a consensus analysis, followed by Kaplan–Meier survival analysis to evaluate the impact of methylation patterns of consensus stage-salient biomarkers on disease prognosis.Results: We found significant genome-wide changes in methylation patterns in cancer cases relative to controls agnostic of stage. Our stage-differentiated analysis yielded the following stage-salient genes: one stage-I gene (FBN1), one stage-II gene (FOXG1), one stage-III gene (HCN1) and four stage-IV genes (NELL1, ZNF135, FAM123A, LAMA1). All the biomarkers were hypermethylated, indicating down-regulation and signifying a CpG island Methylator Phenotype (CIMP) manifestation. A significant prognostic signature consisting of FBN1 and FOXG1 survived all the steps of our analysis pipeline, and represents a novel early-stage biomarker. Conclusions: We have designed a workflow for stage-differentiated consensus analysis, and identified stage-salient diagnostic biomarkers and an early-stage prognostic biomarker panel. Our studies further yield a novel CIMP-like signature of potential clinical import underlying CRC progression.

s.Two Implementation and Accountability, 8 Justiciability of Human Rights for Health

2020 ◽  
Author(s):  
Flood Colleen M ◽  
Thomas Bryan
Keyword(s):  
Public Health ◽  
Human Rights ◽  
Right To Health ◽  
Health And Human Rights ◽  
Proper Role ◽  
Health Related ◽  
State Obligations ◽  
The Right ◽  
The Impact

This chapter examines both the power and limitations of litigation as a means of facilitating accountability for the advancement of public health. While almost half of the world’s constitutions now contain a justiciable right to health, the impact of litigation has been mixed. Judicial accountability has, in some cases, advanced state obligations to realize the highest attainable standard of health, but in other cases, litigation has threatened the solidarity undergirding public health systems. There is significant country-to-country variation in interpreting health-related human rights, as well as differing views of the proper role of courts in interpreting and enforcing these rights. Surveying regional human rights systems and national judicial efforts to address health and human rights, it is necessary to analyze how courts have approached—and how they should approach—litigation of the right to health and health-related human rights to improve health for all.

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