scholarly journals Prognostic significance of macrosatellite instability in patients under 50 years of age suffering from colorectal cancer

2009 ◽  
Vol 62 (5-6) ◽  
pp. 217-223
Author(s):  
Atila Fenjvesi
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Prognostic Significance ◽  
Young Patients ◽  
Dna Mismatch ◽  
Significant Difference ◽  
Sporadic Cases ◽  
Microsatellite Stability ◽  
Better Than

Introduction Colorectal cancer (CRC) can arise through two distinct mutational pathways: microsatellite instability or chromosomal instability. High-frequency microsatellite instability (MSI) occurs in approximately 15 percent of sporadic cases of CRCs. Many studies have well established that MSI, the hallmark of defective DNA mismatch repair, is associated with prolonged survival of CRC patients compared with tumors that are microsatellite stable. CRCs in patients under 50 years of age are rare and represent about 5% of the total number of tumors. The aim of this study was to analyze the prognostic significance of MSI in CRC patients younger than 50 at the time of diagnosis. Material and methods 31 patients with CRC under 50 years of age were tested for the presence of MSI, and compared with 35 patients aged 50 or more at the time of diagnosis. CRC-specific survival five-year- follow-up period was analyzed in relation to MSI status. Results The frequency of MSI among the young patients was 35.48%, which was significantly higher than the rate of 11.43% noted in older patients with CRCs (p<0.042). This study revealed no difference in survival in patients with CRCs aged less than 50 compared with those over 50 years of age. The five-years survival of young CRCs patients with MSI 81.82%, was better than that of the patients with cancers with microsatellite stability, 60%, but there was no significant difference in statistics. Discussion and conclusion In our study there was no statistically detectable significant difference between tumor microsatellite status and survival in young patients, although we confirmed the previous observations that MSI is associated with better prognosis. We found that the pathological stage of CRC was an independent and powerful predictor of the clinical outcome.

Role of MSI and DCC status to predict response to FOLFOX in metastatic colorectal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21056-21056
Author(s):  
M. Bennamoun ◽  
O. Schischmanoff ◽  
A. Martin ◽  
P. Mariani ◽  
L. Ah Koon ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Protein Expression ◽  
Microsatellite Instability ◽  
Disease Free Survival ◽  
Current Treatment ◽  
Metastatic Colon Cancer ◽  
Significant Difference ◽  
Microsatellite Stability

21056 Background: Microsatellite instability (MSI) and lack of Deleted Colon Cancer (DCC) protein expression have been observed respectively in ∼15% and 70% of colon cancer cases and are considered as prognostic factors in colorectal cancer (CRC). In adjuvant setting these markers could be considered to decide treatment. We know that MSI colon cancer do not benefit from 5Fluorouracyl (5FU)-based chemotherapy. A current treatment of reference for colon cancer is a combination of 5FU and Oxaliplatin (FOLFOX). Our aim was to determine whether MSI status or DCC expression are predictive markers of FOLFOX efficiency in patients with metastatic CRC. Methods: Tumour specimens were collected from patients with metastatic colon cancer treated with FOLFOX. The FOLFOX regimen was evaluated in first line treatment according to the WHO criteria. The microsatellite instability status was assessed by measurement of the length of five monomorphic mononucleotide markers. DCC protein expression were evaluated by immunohistochemistry. Results: Forty patients (22 men, 18 women), median age 63.5 years (27–83) were treated with FOLFOX. Nine patients had tumours exhibiting high microsatellite instability (microsatellite instability group, MSI group) and 31 patients had tumours exhibiting microsatellite stability (microsatellite stable group, MSS group). In MSS group, we observed 11 partial responses (36%) and only two in MSI group (22%) (not significant difference). Both disease free survival and overall survival were not significantly different for MSI and MSS groups. Determination of DCC status is under investigation. Conclusions: There was no significant difference in chemosensitivity to FOLFOX for MSI and MSS metastatic patients. Therefore FOLFOX regimen could be proposed to metastatic patients irrespective of MSI status. The study of the relationship between DCC expression and response to FOLFOX is ongoing. No significant financial relationships to disclose.

Clinical implications of microsatellite instability in mucinous colorectal cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 657-657
Author(s):  
Fergus Keane ◽  
Darrell Martin ◽  
Gregory D. Leonard ◽  
Sean Hynes ◽  
Margaret Sheehan
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Who Classification ◽  
Prognostic Significance ◽  
Stage Ii ◽  
Stage Iii ◽  
Low Grade ◽  
Tumor Type ◽  
Response To Chemotherapy ◽  
Microsatellite Stability

657 Background: Colorectal Cancer(CRC) is becoming increasingly recognised as a heterogeneous tumor type. Mucinous histological subtype is identified in 10-15% of CRCs, most commonly those with microsatellite instability (MSI), and has traditionally been associated with unfavorable outcomes and poor response to chemotherapy. In contrast, MSI is associated with relatively favourable pathological features and better outcomes, compared with CRCs with microsatellite stability (MSS), such that under the 2010 WHO classification, MSI mucinous CRC is considered low grade, while MSS mucinous CRC is classified as high grade. The aim of this study is to establish the significance of microsatellite stability status in non-metastatic mucinous colorectal cancer. Methods: Between 2010 and 2017, 69 patients with stage II or stage III mucinous colorectal cancer were identified. Microsatellite status was tested in all patients (MSS or MSI), and histological and clinical data, as well as recurrence rates, were assessed in both groups. MSI status was established using polymerase chain reaction(PCR) technique. Results: Sixty-nine patients with mucinous CRC were identified. The median age for the entire group was 73 years (range 32-87), no difference in gender was identified. 63%(n=43) and 37%(n=26) were stage II and stage III respectively at diagnosis. The majority of mucinous CRCs were right-sided (72%). 33% (n=23) were identified as microsatellite unstable (MSI). MSI status was associated with right sided tumours (78% right-sided vs 22% left-sided, p<0.05), older age at diagnosis (mean 76 years vs 68 years, p=0.01), and lower TNM staging at diagnosis (83% vs 52% diagnosed stage 2, p=0.007) compared with the MSS group. A lower disease recurrence rate was identified in the MSI group (4.3% vs 13% in MSS group) at median follow-up time of 33 months (range 8-93 months). Conclusions: In patients with mucinous colorectal cancer, MSI status is a useful marker of favourable histological and clinical features, and is associated with better outcomes. Our study supports the current 2010 WHO classification, and highlights the clinical and prognostic significance of MSI status in this patient cohort.

TUMOUR PATHOLOGY PREDICTS MICROSATELLITE INSTABILITY IN A POPULATION-BASED SERIES OF COLORECTAL CANCER CASES

2008 ◽  
Vol 31 (4) ◽  
pp. 12
Author(s):  
A J Hyde ◽  
D Fontaine ◽  
R C Green ◽  
M Simms ◽  
P S Parfrey ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Population Based ◽  
Pathological Features ◽  
Predictive Tool ◽  
Entire Cohort ◽  
Dna Mismatch ◽  
Bethesda Guidelines ◽  
Revised Bethesda Guidelines

Background: Lynch Syndrome is an autosomal dominant trait that accounts forapproximately 3% of all cases of colorectal cancer (CRC). It is caused by mutations in DNA mismatch repair (MMR) genes, most commonly MLH1 or MSH2. These MMR defects cause high levels of microsatellite instability (MSI-H) in the tumours. MSI testing of all CRCs to identify potential Lynch Syndrome cases is not practical, so the Bethesda Guidelines, which use clinical and pathological features, were created to identify those tumours most likely to be MSI-H^1. In 2007 Jenkins et. al. created MsPath, a tool based on the pathological features described in the rarely used 3^rd Bethesda criterion, to improve prediction of MSI-H tumours among CRC cases diagnosed before age 60 years^2. Methods: We collected a population-based cohort of 716 CRC cases diagnosed before age 75 years in Newfoundland. For each of these cases we collected family history, performed MSI analysis, and scored a number of pathological features for the purpose of evaluating the accuracy of the Bethesda Criteria and MsPath at predicting MSI-H tumours. Results: Our work validates the MsPath tool in the Newfoundland population for the same age group used to create the tool. We found it identified MSI-H cases with a sensitivity of 95% and specificity of 35% in our population of CRCcases diagnosed before age 60 years (n=290). We also tested this tool on our older population of CRCcases, diagnosed at ages 60 to 74 years (n=426). We found it to be at least as predictive in this population,with a sensitivity of 95% and a specificity of 42%. We then used our entire cohort (N=716) to compare MsPath with the other Bethesda criteria.Bethesda criteria 1, 2, 4 and 5 together predicted MSI-H cases with a sensitivity of 67% and a specificity of 51%. MsPath was better at identifying these cases, with a sensitivity of 95% and a specificity of 39%. Conclusions: We conclude that MsPath can be extended to include patients diagnosed with CRC before age 75 years. As well, we have found that MsPath is a better predictive tool than the Revised Bethesda Guidelines for identifying MSI-H cases within a population-based setting of colorectal cancer. References: 1. Umar, A. et. al. J Natl Cancer Inst 2004;96:261-8 2.Jenkins, M.A. et. al. Gastroenterology 2007;133:48-56

Six-month outcomes of a high intensity exercise programme in young patients with hypertrophic cardiomyopathy: The SAFE-HCM trial

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
J Basu ◽  
S Jayakumar ◽  
C Miles ◽  
G Parry-Williams ◽  
H Maclachlan ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
High Intensity ◽  
Young Patients ◽  
Exercise Adherence ◽  
Exercise Programme ◽  
Exercise Group ◽  
Moderate Intensity ◽  
Psychological Benefits ◽  
Significant Difference

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Cardiac Risk in the Young Background Moderate intensity exercise training in older patients with hypertrophic cardiomyopathy (HCM) can improve functional capacity, without significant harm. However, younger patients are attracted to high intensity training (HIT) regimes. The SAFE-HCM study demonstrated that an individually tailored, HIT programme in young patients with HCM was feasible, and provided both health and psychological benefits, without an increase in the burden of arrhythmia. Purpose To assess whether observed benefits of a HIT programme in young patients with HCM are sustained at 6 months. Methods Eighty patients with HCM (45.7y+/-8.6) underwent baseline clinical and psychological assessment. Individuals were randomised to a 12-week HIT programme (n = 40) or usual care (n = 40). Baseline evaluation was repeated at 12 weeks (T12). Feasibility, safety, health and psychological benefits were assessed. At 12-weeks individuals were encouraged to continue with the frequency and intensity of physical activity (PA) achieved at the end of the cardiac rehabilitation programme. Participants in the exercise arm were invited to follow-up at 6 months (T6m). Results The majority (83%) of participants completed the 12-week study. At T12 there was no significant difference between groups in the composite arrhythmia safety outcome (p = 0.99). The indices of exercise capacity were significantly improved in the exercise compared to the control group; peak VO2 (+3.7ml/kg/min [CI 1.1,6.3], p = 0.006), VO2/kg at anaerobic threshold (VO2/kgAT) (+2.44ml/kg/min [CI 0.6,4.2], p = 0.009), time to AT (+115s [CI 54.3,175.9], p &lt; 0.001) and exercise time (max ET) (+108s [CI 33.7,182.2], p = 0.005). The exercise group also demonstrated greater reduction in systolic BP (-7.3mmHg [CI -11.7,-2.8], p = 0.002), BMI (-0.8kg/m2 [CI-1.1,-0.4], p &lt; 0.001), anxiety (-2.6 [CI-3.6,-1.6], p= &lt;0.001) and depression (-1.1 [CI -2.0,-0.2], p = 0.015) scores. At T6m patient reported exercise adherence was comparable to baseline PA in 33/34 of the exercise group attending for follow up. Most exercise gains dissipated with the exception of time to AT (p = 0.002), max ET (p = 0.003), VO2/kgAT (p = 0.04) and anxiety score (p &lt; 0.001) (Figure 1). There were no sustained episodes of atrial or ventricular arrhythmias. The incidence of NSVT did not differ between time points (p = 0.09). Conclusion A 12-week HIT programme in young patients with HCM offers considerable gains in fitness and psychological outcomes, with no increase in arrhythmic burden. At T6m exercise levels as well as most physiological adaptations and health benefits returned to baseline, as seen in other studies when formal participation in an exercise programme comes to an end. This highlights the importance of the implementation of strategies to encourage ongoing engagement in PA. Potential solutions include identification of barriers to exercise, as well as adoption of novel tele-rehabilation approaches. Abstract Figure 1 Sustained benefits at T6m

scholarly journals Cyclin D1 G870A Variant is Associated with Increased Risk of Microsatellite Instability-Positive Colorectal Cancer in Young Male Patients

2007 ◽  
Vol 10 (2) ◽  
pp. 29-36
Author(s):  
T Josifovski ◽  
N Matevska ◽  
M Hiljadnikova-Bajro ◽  
Z Sterjev ◽  
A Kapedanovska ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Cyclin D1 ◽  
Regulatory Protein ◽  
Significant Risk ◽  
Young Male ◽  
Genotype Distribution ◽  
Increased Risk ◽  
Significant Difference ◽  
Male Patients

Cyclin D1 G870A Variant is Associated with Increased Risk of Microsatellite Instability-Positive Colorectal Cancer in Young Male PatientsCyclin D1 (CCND1) is a cell cycle regulatory protein, which is often over expressed in human tumors and is associated with cell proliferation and poor prognosis. A common G870A single nucleotide polymorphism at codon 242 in exon 4 of the CCND1 gene is associated with an altered messenger RNA transcript and increased risk of colorectal cancer (CRC) and adenoma in some studies. Over expression of CCND1 modifies the effect of mutations in mismatch repair (MMR) genes, enhances microsatellite instability (MSI), and influences the age ofonset of hereditary non polyposis colorectal cancer (HNPCC). We have extended our study that indicated that the CCND1 A variant may influence the age of onset of CRC in the Macedonian population only in patients who exhibit MSI tumors by a case control study of 331 randomly selected CRC patients and 101 controls without clinical diagnosis of CRC. We did not observe a significant difference in overall allelic frequencies and genotype distribution of affected and unaffected mutation carriers, but found a statistically significant risk of CRC in carriers of the CCND1 A allele when patients were grouped according to gender, age and MSI status. A higher risk was observed in patients with MSI-positive tumors and particularly in male patients under 60 years of age. The consequences of the above observation were reversed in female patients. These results indicate that the CCND1 A variant may enhance CRC progression through a pathway influenced by estrogens in colonic epithelia.

Effects of Orthokeratology Lens On Axial Length Elongation in Myopia With Anisometropia Children

2021 ◽  
Author(s):  
Ziyang Chen ◽  
Kai-Ming Chen ◽  
Ying Shi ◽  
Zhao-Da Ye ◽  
Sheng Chen ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Axial Length ◽  
Statistical Significance ◽  
Spherical Equivalent ◽  
Significant Difference ◽  
The Mean ◽  
The Difference ◽  
Better Than ◽  
Group 1

Abstract AimTo investigate the effect of orthokeratology (OK) lens on axial length (AL) elongation in myopia with anisometropia children.MethodsThirty-seven unilateral myopia (group 1) and fifty-nine bilateral myopia with anisometropia children were involved in this 1-year retrospective study. And bilateral myopia with anisometropia children were divided into group 2A (diopter of the lower SER eye under − 2.00D) and group 2B(diopter of the lower SER eye is equal or greater than − 2.00D). The change in AL were observed.The datas were analysed using SPSS 21.0.Results(1) In group 1, the mean baseline AL of the H eyes and L eye were 24.70 ± 0.89 mm and 23.55 ± 0.69 mm, respectively. In group 2A, the mean baseline AL of the H eyes and L eyes were 24.61 ± 0.84 mm and 24.00 ± 0.70 mm respectively. In group 2B, the mean baseline AL of the H eyes and L eyes were 25.28 ± 0.72 mm and 24.70 ± 0.74 mm. After 1 year, the change in AL of the L eyes was faster than the H eyes in group 1 and group 2A (all P<0.001).While the AL of the H eyes and L eyes had the same increased rate in group 2B. (2) The effect of controlling AL elongation of H eyes is consistent in three groups (P = 0.559).The effect of controlling AL elongation of L eyes in group 2B was better than that in group 1 and group 2A (P < 0.001). And the difference between group 1 and group 2A has no statistical significance. (3) The AL difference in H eyes and L eyes decreased from baseline 1.16 ± 0.55mm to 0.88 ± 0.68mm after 1 year in group 1.And in group 2A, the AL difference in H eyes and L eyes decreased from baseline 0.61 ± 0.34mm to 0.48 ± 0.28mm. There was statistically significant difference (all P<0.001). In group 2B, the baseline AL difference in H eyes and L eyes has no significant difference from that after 1 year (P = 0.069).ConclusionsMonocular OK lens is effective on suppression AL growth of the myopic eyes and reduce anisometropia value in unilateral myopic children. Binocular OK lenses only reduce anisometropia with the diopter of the low eye under − 2.00D. Binocular OK lenses cannot reduce anisometropia with the diopter of the low eye equal or greater than − 2.00D. Whether OK lens can reduce refractive anisometropia value is related to the spherical equivalent refractive of low refractive eye in bilateral myopia with anisometropia children after 1-year follow-up.

Microsatellite Instability as a Predictor of Outcomes in Colorectal Cancer in the Era of Immune-Checkpoint Inhibitors

2021 ◽  
Vol 22 ◽  
Author(s):  
Csongor György Lengyel
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Immune Checkpoint ◽  
Predictive Value ◽  
Checkpoint Inhibitors ◽  
Tumor Infiltrating Lymphocytes ◽  
Primary Objective ◽  
Dna Mismatch ◽  
Dominant Component ◽  
Colon Cancers

: The microsatellite instable phenotype resulting from errors in DNA mismatch repair proteins accounts for as far as 15 to 20% of non-hereditary colon cancers but is scarce in rectal cancer. It has been shown that the increased existence of tumor-specific neoantigens in hypermutated tumors is correlated with higher tumor-infiltrating lymphocytes (TILs) and overexpression of immune checkpoint receptors and ligands, mainly PD-1 and PD-L1. In particular, the data gained up to now gives evidence that neoantigen recognition constitutes a dominant component in the course of immunotherapies. This review's primary objective is to describe current approvals and summarize present knowledge about the outcomes of immuno-oncology treatment of microsatellite instable colorectal cancer (CRC). The secondary objective is to give a narrative report about testing methodologies, prognostics, and the predictive value of microsatellite instability. For this purpose, a literature review was performed, focusing on published clinical trial results, ongoing clinical trials and timelines, testing methods, and prognostic and predictive value of MSI. Following four recent FDA approvals of immunotherapy of MSI-high CRC, further work should be warranted by pathology societies towards standardization and rising concordance and reproducibility across the IHC/MSI testing landscape in order to facilitate professionals to offer better survival options for patients with CRC.

The Relationship Between N-Terminal Pro-Brain Natriuretic Peptide Level and Myocardial Performance Index and Their Prognostic Importances in Patients With Acute Myocardial Infarction in Short Term Follow-up

2020 ◽  
Vol 1 (1) ◽  
pp. 12-17
Author(s):  
Mehmet Küçükosmanoğlu ◽  
Cihan Örem
Keyword(s):  
Heart Failure ◽  
Prognostic Significance ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ejection Time ◽  
Ventricular Ejection Fraction ◽  
Significant Difference ◽  
The Mean ◽  
The Relationship

Introduction: MPI is an echocardiographic parameter that exibit the left ventricular functions globally. NT-proBNP  is an important both diagnostic and prognostic factor in heart failure. In this study, we aimed to investigate the prognostic significance of serum NT-proBNP levels and MPI in patients with STEMI. Method: Totally 104 patients with a diagnosis of STEMI were included in the study. Patients followed for 30-days and questioned for presence of symptoms of heart failure (HF) and cardiac death. Patients were invited for outpatient control after 30-days and were divided into two groups: (HF (+) group) and (HF (-) group). Results: Totally 104 patients with STEMI were hospitalized in the coronary intensive care unit. Of those patients, 17 were female (16%), 87 were male (84%), and the mean age of the patients was 58.9±10.8 years. During the 30-day follow-up, 28 (27%) of 104 patients developed HF. The mean age, hypertension ratio and anterior STEMI rate were significantly higher in the HF (+) group compared to the HF (-) group. Ejection time (ET) and left ventricular ejection fraction (LVEF) were significantly lower and MPI was significantly higher in the HF (+) group. When the values on day first and  sixth were compared, NT-ProBNP levels were decreased in both groups. There was no significant difference between the two groups in terms of the change in MPI values on the first and sixth days. Multiple regression analysis showed that the presence of anterior MI, first day NT-proBNP level and LVEF were independently associated with development of HF and death. Conclusion: In our study, NT-proBNP levels were found to be positively associated with MPI in patients with acute STEMI. It was concluded that the level of NT-proBNP detected especially on the 1st day was more valuable than MPI in determining HF development and prognosis after STEMI.  

scholarly journals A Comparison of 940 nm Diode Laser and Cryosurgery With Liquid Nitrogen in the Treatment of Gingival Physiologic Hyperpigmentation Using Split Mouth Technique: 12 Months Follow Up

2019 ◽  
Vol 10 (2) ◽  
pp. 131-138
Author(s):  
Leila Jokar ◽  
Mojtaba Bayani ◽  
Hamid Hamidi ◽  
Mohammad Keivan ◽  
Saranaz Azari-Marhabi
Keyword(s):  
Liquid Nitrogen ◽  
Diode Laser ◽  
Randomized Study ◽  
Facial Esthetics ◽  
Surgical Methods ◽  
Significant Difference ◽  
Treatment Procedures ◽  
Gingival Depigmentation ◽  
Better Than

Introduction: Gingival hyperpigmentation is excessive deposition of melanin pigments in the epithelium of gingiva which affects facial esthetics. Various surgical methods for gingival depigmentation have been used to treat the darkened color of pigmented gingiva. This study compared the use of 940 nm diode laser and liquid nitrogen cryosurgery in the treatment of gingival physiologic hyperpigmentation in terms of gingival depigmentation, postoperative pain, healing duration, pigmentation recurrence, and patients’ satisfaction. Methods: Fifteen systemically healthy patients (11 females and 4 males; 17-35 years of age) with bilateral gingival physiologic hyperpigmentation were enrolled in this split-mouth randomized study. Maxillary anterior labial gingiva of each patient was divided into left and right halves, and each half was randomly depigmented by either laser or cryosurgery. Patients were given questionnaires to evaluate the procedures and were followed up in 3, 7, 10, 17 and 21 days postoperatively for the assessment of gingival healing and 1, 3, 6 and 12 months after the treatments to detect any sign of pigmentation recurrence. Results: The severity of post-op pain measured by visual analogue scale (VAS) was mild to average and showed no significant difference between the 2 modalities (P>0.05). There was no considerable swelling or hemorrhage after the treatment procedures and the healing duration was significantly shorter in laser (P<0.05). The degree of pigmentation in all gingival sites treated by laser reached and remained at zero until the last follow up (1 year) and reached zero in 9 out of 15 cryosurgerytreated sites. All patients were completely satisfied with the laser, and 9 out of 15 were completely satisfied with cryosurgery. No pigmentation recurrence was observed during any follow-up periods. Conclusion: Removal of gingival physiologic hyperpigmentation by laser therapy and cryotherapy was effective and safe. The efficiency of the laser was better than cryotherapy.

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