| 1. |
- Gkekas, Ioannis, et al.
(författare)
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Deficient mismatch repair as a prognostic marker in stage II colon cancer patients
- 2019
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Ingår i: European Journal of Surgical Oncology. - : Elsevier. - 0748-7983 .- 1532-2157. ; 45:10, s. 1854-1861
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A number of reports have evaluated the relationship between deficient DNA mismatch repair (dMMR) and colorectal cancer prognosis. Unfortunately, the exact prognostic role of dMMR has not been clearly established due to contradictory results. This study aims to determine the prognostic impact of dMRR in stage II colon cancer patients only. The appropriate identification of high-risk stage II colon cancers is of paramount importance in the selection of patients who may benefit from adjuvant treatment after surgery.METHODS: Four hundred and fifty-two patients with curative resection of stage II colon cancer were included. Hospital records were used as data source, providing clinical, surgical, pathology, oncology and follow-up information for statistical analysis focusing on overall survival (OS) and time to progression (TTP). Mismatch repair status was determined by immunohistochemistry. Patient survival was followed-up for a mean of 77·35 months.RESULTS: dMMR was detected in 93 of 452 patients (20·6%). No impact on overall survival (Log-Rank, p = 0·583, 95% CI 0·76-1·67). However, the hazard ratio 0·50 for TTP was highly significant (Log-Rank, p = 0·012, 95% CI 0·28-0·87) in patients with dMMR compared with those with mismatch repair proficient tumours (pMMR).CONCLUSIONS: Patients with dMMR tumours have a lower risk for recurrence compared to those with pMMR tumours, but this finding did not correlate to better overall survival.
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| 2. |
- Gkekas, Ioannis, et al.
(författare)
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Microsatellite instability as a prognostic factor in stage II colon cancer patients : a meta-analysis of published literature
- 2017
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Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 37:12, s. 6563-6574
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND/AIM: The prognostic role of microsatellite instability (MSI) in stage II colon cancer patients remains controversial despite the fact that it has been investigated in a number of studies. Hazard ratios differ considerably among these studies. We performed a meta-analysis to define the significance of MSI in this group of patients.MATERIALS AND METHODS: Studies indexed in PubMed presenting separate data on MSI status and survival outcomes for stage II colon cancer patients have been analyzed using fixed-effect meta-analysis of hazard ratio (HR) according to the method of Peto.RESULTS: Analysis was performed on 19 studies including 5,998 patients. A 47.3% of patients received postoperative chemotherapy and included 52.8% males and 47.2% females. Eight studies included some rectal cancer patients although this cohort was not clearly defined in 3 of these. MSI observed in 20.8% (mean) of patients (median 19.9%). HR for overall survival (OS) of MSI vs. microsatellite stable (MSS) tumors for the entire population: 0.73 (95% confidence interval (CI)=0.33-1.65); HR for disease-free survival (DFS):0.60 (95%CI=0.27-1.32). No statistical significant difference was found when studies analyzing MSI with genotyping (MG) and immunohistochemistry (IHC) were compared separately (MG vs. IHC: HR OS 0.45, 95%CI=0.10-2.05 vs. 0.95, 95%CI=0.57-1.58; HR DFS 0.51, 95%CI=0.14-1.85 vs. 0.67, 95%CI=0.26-1.70). However, numerically MSI determination with genotyping shows significantly lower hazard ratios for both DFS and OS. Separate analysis of studies describing colon cancer patients only showed HR OS 0.72 (95%CI=0.31-1.71); HR DFS 0.60 (95%CI=0.27-1.31).CONCLUSION: No significant relation was found between MSI status and OS or DFS. Routine determination of MSI status to guide postoperative management of stage II colon cancer patients cannot be recommended. New large scale high quality studies are needed to answer this question definitively, since currently analyzed studies vary considerably.
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| 3. |
- Patti, Giuseppe, et al.
(författare)
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Net Clinical Benefit of Non-Vitamin K Antagonist vs Vitamin K Antagonist Anticoagulants in Elderly Patients with Atrial Fibrillation
- 2019
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Ingår i: American Journal of Medicine. - : Elsevier BV. - 0002-9343. ; 132:6, s. 5-757
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Tidskriftsartikel (refereegranskat)abstract
- Background: The risks of thromboembolic and hemorrhagic events in patients with atrial fibrillation both increase with age; therefore, net clinical benefit analyses of anticoagulant treatments in the elderly population are crucial to guide treatment. We evaluated the 1-year clinical outcomes with non-vitamin-K antagonist and vitamin K antagonist oral anticoagulants (NOACs vs VKAs) in elderly (≥75 years) patients with atrial fibrillation in a prospective registry setting. Methods: Data on 3825 elderly patients were pooled from the PREFER in AF and PREFER in AF PROLONGATION registries. The primary outcome was the incidence of the net composite endpoint, including major bleeding and ischemic cardiovascular events on NOACs (n = 1556) compared with VKAs (n = 2269). Results: The rates of the net composite endpoint were 6.6%/year with NOACs vs 9.1%/year with VKAs (odds ratio [OR] 0.71; 95% confidence interval [CI], 0.51-0.99; P =.042). NOAC therapy was associated with a lower rate of major bleeding compared with VKA use (OR 0.58; 95% CI, 0.38-0.90; P =.013). Ischemic events were nominally reduced too (OR 0.71; 95% CI, 0.51-1.00; P =.050). Major bleeding with NOACs was numerically lower in higher-risk patients with low body mass index (BMI; OR 0.50; 95% CI, 0.22-1.12; P =.07) or with age ≥85 years (OR 0.44; 95% CI, 0.13-1.49; P =.17). Conclusions: Our real-world data indicate that, compared with VKAs, NOAC use is associated with a better net clinical benefit in elderly patients with atrial fibrillation, primarily due to lower rates of major bleeding. Major bleeding with NOACs was numerically lower also in higher-risk patients with low BMI or age ≥85 years.
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| 4. |
- Patti, Giuseppe, et al.
(författare)
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Thromboembolic and bleeding risk in obese patients with atrial fibrillation according to different anticoagulation strategies
- 2020
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 318, s. 67-73
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Tidskriftsartikel (refereegranskat)abstract
- Background: Data on the relationship between body mass index (BMI), thromboembolic events (TEE) and bleeding in patients with atrial fibrillation (AF) are controversial, and further evidence on the risk of such events in obese patients with AF receiving different anticoagulant therapies (OAC) is needed. Methods and results: We divided a total of 9330 participants from the prospective PREFER in AF and PREFER in AF PROLONGATION registries into BMI quartiles at baseline. Outcome measures were TEE and major bleeding complications at the 1-year follow-up. Without OAC, there was a ≥6-fold increase of TEE in the 4th vs other BMI quartiles (P =.019). OAC equalized the rates of TEE across different BMI strata. The occurrence of major bleeding was highest in patients with BMI in the 1st as well as in the 4th BMI quartile [OR 1.69, 95% CI 1.03–2.78, P =.039 and OR 1.86, 95% CI 1.13–3.04, P =.014 vs those in the 3rd quartile, respectively]. At propensity score-adjusted analysis, the incidence of TEE and major bleeding in obese patients receiving non-vitamin K antagonist oral anticoagulants (NOACs) or vitamin K-antagonist anticoagulants (VKAs) was similar (P ≥.34). Conclusions: Our real-world data suggest no obesity paradox for TEE in patients with AF. Obese patients are at higher risk of TEE, and here OAC dramatically reduces the risk of events. We here found a comparable clinical outcome with NOACs and VKAs in obese patients. Low body weight and obesity were also associated with bleeding, and therefore OAC with the best safety profile should be considered in this setting.
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