Evolution of Laparoscopic Surgery for Colorectal Cancer: The Impact of the Clinical Outcomes of Surgical Therapy Group Trial

2016 ◽  
Vol 82 (8) ◽  
pp. 685-691 ◽  
Author(s):  
Michelle Julien ◽  
James Dove ◽  
Kevin Quindlen ◽  
Kristen Halm ◽  
Mohsen Shabahang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Outcomes ◽  
Surgical Therapy ◽  
Early Stage ◽  
Therapy Group ◽  
Oncologic Outcomes ◽  
Tumor Stages ◽  
The Cost ◽  
The Impact ◽  
Colorectal Resections

The Clinical Outcomes of Surgical Therapy Group (COST) Trial established laparoscopic procedures offer short-term benefits while preserving the same oncologic outcomes in colorectal cancer (CRC) patients compared with open procedures. The aim of this study was to evaluate the trend of laparoscopic resection for CRC before and after the publication of the COST Trial. Retrospective study of surgically treated CRC patients was conducted from January 2000 to December 2009. Surveillance, Epidemiology, and End Results Program and Medicare. Between 2000 and 2009, 147,388 patients underwent resection for CRC, 9,901 resections were performed laparoscopically. In 2000, 1.0 per cent of colorectal resections were performed laparoscopically. There was a dramatic increase in laparoscopic resections in 2009 to 30.4 per cent. During this time period, rates of laparoscopic resections increased for all tumor stages. Right colectomies and early stage tumors had the most significant rise from 3.1 per cent (2004) to 38.7 per cent (2009) and 4.41 per cent (2004) to 39.17 per cent (2009), respectively; whereas, rectal and later stage tumors resection rates were more modest from 2.1 per cent (2004) to 13.2 per cent (2009) and 1.41 per cent (2004) to 17.10 per cent (2009), respectively. This study demonstrates the COST Trial had a significant impact on utilization of laparoscopic colorectal resection for CRC. Although laparoscopic colorectal resections have been accepted for all types of CRCs, more difficult procedures are being adopted at slower rates.

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.

scholarly journals miR-224 targets BTRC and promotes cell migration and invasion in colorectal cancer

3 Biotech ◽  
2020 ◽  
Vol 10 (11) ◽  
Author(s):  
Qi Zheng ◽  
Jane J. Yu ◽  
Chenggang Li ◽  
Jiali Li ◽  
Jiping Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Migration ◽  
Protein Expression ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Normal Tissues ◽  
The Impact

AbstractOur study aims to investigate the impact of miR-224 on cell migration and invasion in colorectal cancer (CRC) as well as its molecular mechanisms. The results showed that miR-224 was significantly upregulated in CRC compared to normal tissues via the TCGA database. Overexpression of miR-224 promoted CRC cell migration and invasion, while inhibition of miR-224 demonstrated the opposite result via transwell assays. In addition, we found that BTRC was a target gene of miR-224 through the miRecords database and dual-luciferase assay, while western blot together with RT-qPCR showed that inhibition of miR-224 led to elevated BTRC expression in protein level but not in mRNA level, and also decreased the expression of β-catenin. In reference to the Human Protein Atlas, BTRC protein expression was higher in normal tissues than in CRC tissues. In conclusion, miR-224 regulates its target BTRC protein expression and its related Wnt/β-catenin pathway. Its impact on cell migration and invasion in CRC cells suggested that miR-224 could be a prospective therapeutic target for early-stage non-metastatic CRC.

Impact of colonoscopy screening on individuals at high risk of hereditary nonpolyposis colorectal cancer (HNPCC).

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 384-384
Author(s):  
C. Guillen-Ponce ◽  
C. Martinez-Sevila ◽  
R. Jover ◽  
R. Perea ◽  
M. Molina-Garrido ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Early Stage ◽  
Colorectal Adenomas ◽  
Medical Documentation ◽  
Synchronous Tumors ◽  
Colonoscopy Screening ◽  
Amsterdam Criteria ◽  
The Impact

384 Background: Colonoscopy screening reduces the incidence of, and mortality from, colorectal cancer (CRC) in individuals with HNPCC. The aim of this study was to determine the impact of colonoscopic follow-up in individuals at high risk of HNPCC, in terms of detection of precursor lesions (adenomas) or cancer. Methods: Between 2005-2008, 163 individuals with HNPCC were advised to undergo regular follow-up colonoscopy. Compliance and results of the scans were evaluated annually and were verified with medical documentation. Results: Of the 125 individuals who underwent at least one colonoscopy during the follow-up period of colonoscopy screening, in 33 subjects (26%) at least one colonic adenoma was detected. The median number of adenomas detected per colonoscopy in individuals with polyps was 2. The number of colonoscopies with polyps did not differ between women and men. However, the number of polyps removed by colonoscopy and the total number of polyps removed during the follow-up period was significantly higher in men (p = 0.005, p = 0.05 bilateral, respectively). 5 individuals (4%) were diagnosed with CRC, one of whom had two synchronous tumors. Of these, four individuals had properly followed the screening recommendations with the recommended frequency. In the case where two synchronous tumors were detected, it was the first colonoscopy screening that had been performed on the individual. None had had cancer previously, they were healthy relatives of an index case. All except one belonged to families that fulfilled the Amsterdam criteria I / II. All the tumors were diagnosed at an early stage, except two, which exhibited positive nodes. Conclusions: Colonoscopy screening is effective in diagnosing colorectal adenomas and cancer in individuals with HNPCC. Men with HNPCC have a greater number of colorectal adenomas. Screening allows the detection of colorectal cancer at an early stages. Funded by a young researcher's grant from the Spanish Society of Medical Oncology 2006. No significant financial relationships to disclose.

Muscle volume loss after the induction of first-line chemotherapy as a novel prognostic factor in metastatic colorectal cancer patients.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 558-558
Author(s):  
Yusuke Yoshikawa ◽  
Koji Okabayashi ◽  
Hirotoshi Hasegawa ◽  
Masashi Tsuruta ◽  
Ryo Seishima ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Tumor Response ◽  
Muscle Volume ◽  
Oncologic Outcomes ◽  
Volume Loss ◽  
First Line ◽  
The Impact ◽  
Line Chemotherapy

558 Background: Muscle volume loss (MVL) is observed in end-stage cancer patients as cachexia. However, the impact of MVL on tumor response and survival still remains unclear during chemotherapy in metastatic colorectal cancer (mCRC) patients. The aim of this study is to evaluate correlation between MVL and oncologic outcomes in mCRC patients. Methods: A total of 91 mCRC patients who received first-line chemotherapy were identified in our prospective registry between February 2007 and April 2013. Skeletal muscle index at the level of L3 vertebra (SMI) was calculated by muscle volume normalized by stature at the time of the induction of first-line chemotherapy (bSMI) and first evaluation of tumor response (fSMI). Patients whose SMI decreased more than 10% were classified as MVL group. The impact of these variables on oncologic outcomes (overall survival [OS], progression free survival [PFS], and tumor response rate [RR]) were analyzed. Results: Mean bSMI and fSMI were 35.0 (SD: 7.11) cm2/m2, and 34.2 (SD: 6.85) cm2/ m2, respectively. Eighteen patients were classified into the MVL group. The patients in MVL group significantly responded to the chemotherapy (RR of MVL: 11.1% vs. RR of non-MVL: 49.3%, p < 0.01). There was no significant difference in terms of high grade adverse effect between MVL and non-MVL group. Patients in MVL group had a significant shorter median PFS (MVL: 5.5 [2.5 - 10.1] months vs. non-MVL: 12.8 (3.8-80.5) months, p < 0.01) and median OS (MVL: 13.9 [6.2-61.2] months vs. non-MVL: 29.3 (8.2-94.0) months, p < 0.01). Multivariate analysis demonstrated that patients with MVL had significantly worse prognostic factor (OS: HR 3.51 [1.99-6.21], p < 0.01 and PFS: HR 8.27 [2.91-23.5], p < 0.01. Conclusions: The findings of this study suggested that MVL after the induction of the first line chemotherapy could be a novel predictive factor for chemotherapy response and prognosis. Further investigation should be required to clarify the mechanistic background.

Evaluation of the quality of cancer treatment in a population of patients (pts) with metastatic colorectal cancer (mCRC) in routine clinical practice in different regions of Russia.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18022-e18022
Author(s):  
Mikhail Fedyanin ◽  
Shamai Aliyeva ◽  
Liubov Yu Vladimirova ◽  
Sanal Erdniev ◽  
Alexander Ivanov ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Mortality Rate ◽  
Metastatic Disease ◽  
Early Stage ◽  
Care Organization ◽  
Line Treatment ◽  
The Impact ◽  
Regions Of Russia ◽  
Egfr Antibody

e18022 Background: In Russia, there are no federal screening programs for detecting early stage of colon cancer; therefore we can assess the impact of various factors that could potentially affect the mortality of pts with mCRC Methods: We conducted a survey with 13 question according treatment of pts with CRC in 17 regional comprehensive cancer centers in 14 regions of Russia, with a total population of 26.347 billion. Results of the survey were conducted by methods of descriptive statistics. Effects of factors on mortality rate in regions were analyzed by a regression model Results: Only 34% pts with stage II-III received adjuvant chemotherapy. Mutation status of KRAS gene has been evaluated only in 33% pts with mCRC. In 2013, metastasectomy was performed only 13% of pts. Only 80% of pts who needed systemic treatment received chemotherapy (CT): doublets of CT (XELOX/FOLFOX/FLOX or FOLFIRI/XELIRI/IFL) - 49%, monotherapy of fluoropyrimidines - 39% of pts, bevacizumab – in 14% and anti-EGFR antibodies - 5% pts. Only 14% of pts with mCRC was placed central vein devices. Second line CT was performed in 47% pts: doublets – in 54%, monotherapy of fluoropyrimidines - in 24% pts, bevacizumab - 13% and anti-EGFR antibody - 8%. Third-line treatment was performed in 25% of pts: anti-EGFR antibodies - in 7.5%. According to regression analysis adjuvant chemotherapy (р = 0.01), bevacizumab only in the 1st line (р = 0.01), and installation of central venous devises (р = 0.07) and anti-EGFR antibody in the 1st line (р = 0.1) in wtKRAS pts had independent positive effect on the mortality rate in regions. We revealed a significant reverse connection between a high mortality rate in the region and administration of fluoropyrimidine monotherapy as 1st line treatment of metastatic disease (p = 0.01) Conclusions: The mortality with colorectal cancer is depended of complex factors that reflect the health care organization in the region, both at the stage of treatment of pts with early-stage and metastatic disease. We revealed that targeted agents are the most effective only in the 1st line settings.

The incidence of peritoneal carcinomatosis and impact on outcomes in relapsed early T4 colorectal cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 73-73
Author(s):  
Rosemary Habib ◽  
Val Gebski ◽  
Kenneth Micklethwaite ◽  
Duncan McLeod ◽  
James Toh ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factors ◽  
Peritoneal Carcinomatosis ◽  
Clinical Outcomes ◽  
Proportional Hazards ◽  
Early Stage ◽  
Multivariable Analysis ◽  
Stage Ii ◽  
Tertiary Centre ◽  
T4 Stage

73 Background: There is limited data regarding the association between peritoneal carcinomatosis (PC) and clinical outcomes in colorectal cancer (CRC). We examined the incidence of PC and explored the relationship to survival (RFS & OS) in CRC. Methods: The demographic and clinical details of patients with stage II/III CRC referred to a tertiary centre in Western Sydney between 2009-2016 were obtained. Associations between clinical outcomes and baseline prognostic factors were investigated using proportional hazards regression models. The effect of prognostic factors on outcome were examined by tumour stage. Results: 495 patients were identified, 281 (57%) with stage II and 214 (43%) with stage III. Median follow-up was 38 months. 330 (67%) had T3 and 165 (33%) had T4 disease. Median age at diagnosis was 72 years (19 -94). 104 (21%) patients relapsed, 24 (23%) had PC and of those, 6 had PC as their only site of metastasis. 10% (n = 5) with T3 developed PC compared with 35% (n = 19) with T4 disease (P = 0.02). Compared with non-PC, PC was associated with poorer median OS (28 Vs 46 m; p = 0.03). Median RFS for T3 was 16 months, T4, 14 months (NS). Median OS for T3 was 34 months Vs T4 28 months (P = 0.45). Of those with PC relapse, the diagnosis of PC was highest in the first two years post-operatively (88%). 9 patients (38%) with PC died due to bowel obstruction Vs 4 (5%) patients with non-PC relapse (P < 0.01). Poorer OS was associated with PC (HR 1.74; p = 0.03), right sided primary (HR 1.602; P = 0.05), T4 stage (HR 1.69; P = 0.03), LVI (HR 1.95; p < 0.01), N stage (HR 1.51; P < 0.01), and number of metastases at baseline (HR 1.25; p = 0.04). On multivariable analysis right sided primary and T4 stage remained significant. Conclusions: Patients with PC relapse have an 18 month shorter median OS than those with non-PC relapse. Further, PC recurrence is more common in patients with T4 compared with T3 CRC and was the only site of metastatic disease in 7% of relapsed patients with T4 CRC. Consideration for peritonectomy and/or HIPEC should be given for patients with PC metastases. For patients with resected early stage T4 CRC, consideration should be given for surveillance laparoscopy.

scholarly journals A modeled radiological dispersive device release and the impact to decision-making in an urban environment

2020 ◽  
Vol 35 (4) ◽  
pp. 316-322
Author(s):  
Paulo Oliveira ◽  
Ubiratan Oliveira ◽  
Ricardo Stenders ◽  
Ademir Silva ◽  
Helio Vital ◽  
...  
Keyword(s):  
Decision Making ◽  
Early Stage ◽  
Radioactive Material ◽  
Sensitive Information ◽  
Training Environment ◽  
Stability Class ◽  
Radiological Dispersion Device ◽  
The Stability ◽  
The Cost ◽  
The Impact

A radiological dispersion device is a weapon that combines radioactive material with conventional explosives for spreading radioactive material across an inhabited area. This study is focused on evaluating key parameters in an radiological dispersion device scenario. The calculations were performed to include two different situations: by using explosives and by simple mechanical release. Simulations were conducted with the use of the HotSpot Health Physics Codes. The results suggest the existence of significant correlations between stability classes in scenarios where they evolve with time, producing alternations between them. As long as the stability class remains constant, this latter finding offers the possibility of creating a suitable response, based on temporal evolutions. Therefore, the purpose of this study is to: estimate the size of the potentially affected population, estimate absorbed doses, and estimate the cost-effectiveness in order to help initial responses by providing time-sensitive information about the event. A methodology capable of providing useful information allows prompt decisions and initial assessments of future risks to be made efficiently. This approach can also provide a training environment for the personnel responsible for the decision-making at an early stage of the response.

scholarly journals Obesity And Telomere Status In The Prognosis Of Colorectal Cancer Patients Submitted To Curative Intention Surgical Treatment

2020 ◽  
Author(s):  
Sergio García-Martínez ◽  
Daniel González-Gamo ◽  
Tamara Fernández-Marcelo ◽  
Sofía de la Serna ◽  
Inmaculada Serrano ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Surgical Treatment ◽  
Telomere Length ◽  
Clinical Outcomes ◽  
Published Data ◽  
Prognostic Impact ◽  
Telomere Attrition ◽  
Clinical Evolution ◽  
Obesity Status ◽  
The Impact

Abstract Background The risk of colorectal cancer (CRC) development has been related to telomere dysfunction and obesity. However, prognosis of patients affected by CRC has not clearly established considering both telomere attrition and obesity status. Previous published data highlights the importance of studying how obesity influences telomere function and its potential role as a predictor of prognosis in CRC. The aim of this study was to evaluate the impact of obesity and telomere status in the prognosis of patients affected by CRC and submitted to curative surgical treatment. Methods We performed a prospective study including 162 CRC patients submitted to curative surgical treatment. Samples were obtained from tumor and non-tumor tissues. Subjects were classified according to their Body Mass Index (BMI). Telomere status was established through telomere length and telomerase evaluation. Statistical analyses were performed using the SPSS software package version 22. Differences in two or more groups of study were calculated by parametric or non-parametric tests, depending on normality and homoscedasticity conditions of the variables. Prognosis was analyzed using the Kaplan-Meier method. The potential prognostic impact of the variables considered in this work jointly, was evaluated by Cox multivariate regression analyses. Results Patients with shorter telomeres, both in the tumor (median telomere length < 6.5 kb) and their non-tumor paired tissues (median telomere length < 7.1 kb), had the best clinical evolution, independently of the Dukes' stage of cancers (P = 0.025, for tumor samples; P = 0.003, for non-tumor samples). Telomere shortening was inversely associated with BMI in CRC patients. Also, subjects with a BMI > 31.85kg/m 2 showed the worse clinical outcomes. Of interest, the impact of BMI showed gender dependence, since only the group of men showed significant differences in CRC prognosis in relation to obesity status (P = 0.037). Conclusions Telomere length constitutes a useful biomarker to predict prognosis in CRC. Independently of BMI values, the better clinical evolution was associated with shorter telomeres. Obesity seems to have an impact on the clinical outcomes of CRC; however, the impact of BMI seems to be related to other factors such as gender.

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