Cyclin A and cyclin D1 as significant prognostic markers in colorectal cancer patients

BACKGROUND: Colorectal cancer is a common cancer all over the world. Aberrations in the cell cycle checkpoints have been shown to be of prognostic significance in colorectal cancer. METHODS: The expression of cyclin D1, cyclin A, histone H3 and Ki-67 was examined in 60 colorectal cancer cases for co-regulation and impact on overall survival using immunohistochemistry, southern blot and in situ hybridization techniques. Immunoreactivity was evaluated semi quantitatively by determining the staining index of the studied proteins. RESULTS: There was a significant correlation between cyclin D1 gene amplification and protein overexpression (concordance = 63.6%) and between Ki-67 and the other studied proteins. The staining index for Ki-67, cyclin A and D1 was higher in large, poorly differentiated tumors. The staining index of cyclin D1 was significantly higher in cases with deeply invasive tumors and nodal metastasis. Overexpression of cyclin A and D1 and amplification of cyclin D1 were associated with reduced overall survival. Multivariate analysis shows that cyclin D1 and A are two independent prognostic factors in colorectal cancer patients. CONCLUSIONS: Loss of cell cycle checkpoints control is common in colorectal cancer. Cyclin A and D1 are superior independent indicators of poor prognosis in colorectal cancer patients. Therefore, they may help in predicting the clinical outcome of those patients on an individual basis and could be considered important therapeutic targets

Visfatin and adiponectin as early markers of atherosclerosis in type 2 diabetes mellitus

IntroductionAs cardiovascular disease is the leading cause of mortality in type 2 diabetes mellitus, new markers for early detection and risk stratification of diabetic macroangiopathy and microangiopathy are highly desired. Adipocytokines were considered to lead to an increased risk of vascular complications in patients with type 2 diabetes by modulating vascular function and affecting the inflammatory process, thus enhancing atherosclerosis. Two of these were of particular interest, namely, visfatin and adiponectin. AimThe aim of this study was to evaluate serum visfatin, serum, and urinary adiponectin as early, sensitive surrogate markers of vascular atherosclerosis. We also correlated the levels of these markers to the degree of carotid intimal medial thickness (reflecting the atherosclerotic burden) in type 2 diabetic patients. Results Sixty diabetic patients were subdivided into two groups: group I (30 patients with carotid atherosclerosis as assessed by carotid Doppler) and group II (30 patients without carotid atherosclerosis). Twenty healthy volunteers participated as controls. Serum visfatin as well as serum and urinary adiponectin were assessed in all the study groups. We found significantly higher levels of serum visfatin among diabetics compared with the control group. Visfatin was also significantly higher in group I diabetics with atherosclerosis than those without (P<0.05). Similarly, urinary adiponectin was significantly higher in group I than in group II and in diabetics than in the control group. Serum adiponectin was higher in the control group than both the study groups. Using a regression model, visfatin proved to be the only significant predictor in the model (β=0.03, P<0.001). In fact, visfatin alone proved significant, explaining 63% of the variability in carotid intima-media thickness (P<0.001). Conclusion Serum visfatin is highly correlated with macrovascular complications in diabetic patients. Serum visfatin may emerge as a valuable and cheaper surrogate marker for the prediction of prevalent macrovascular complications in a type 2 diabetic population. It is a novel and easy-to-obtain method for the clinical assessment of vascular stress and cardiovascular disease risk in type 2 diabetes. Future prospective studies are needed to confirm our Results

Pediatric cerebral cavernous malformations and stereotactic radiosurgery: an analysis of 50 cases from a multicentric study

International audienceOBJECTIVE: Cerebral cavernous malformations (CCMs) are the second most common vascular anomaly affecting the CNS in children. Although stereotactic radiosurgery (SRS) has been proposed as an alternative to microsurgery in the management of selected cases in adults, there is a paucity of studies focusing on pediatric patients. The aim of this study was to present the outcomes and associated risks of SRS in this subgroup of patients. METHODS: This retrospective multicenter study included pediatric patients treated with single-session SRS for CCMs. The annual hemorrhage rate (AHR) was calculated before and after SRS in hemorrhagic lesions. The Engel classification was used to describe post-SRS epileptic control. Adverse radiation effects (AREs) and the occurrence of new neurological deficits were recorded. RESULTS: The study included 50 patients (median age 15.1 [IQR 5.6] years) harboring 62 CCMs. Forty-two (84%) and 22 (44%) patients had a history of hemorrhage or epilepsy prior to SRS, respectively. The AHR from diagnosis to SRS excluding the first hemorrhage was 7.19 per 100 CCM-years, dropping to 3.15 per 100 CCM-years after treatment. The cumulative risk of first hemorrhage after SRS was 7.4% (95% CI 0%-14.3%) at 5 years and 23.6% (95% CI 0%-42.2%) at 10 years. Eight hemorrhagic events involving 6 CCMs in 6 patients were recorded in the post-SRS follow-up period; 4 patients presented with transient symptoms and 4 with permanent symptoms. Of the 22 patients with pre-SRS seizures, 11 were seizure free at the last follow-up (Engel class I), 6 experienced improvement (Engel class II or III), 5 had no improvement (Engel class IVA or IVB), and 1 experienced worsening (Engel class IVC). Radiographic AREs were documented in 14.5% (9/62) of CCMs, with 4 being symptomatic. CONCLUSIONS: Single-session SRS reduces the CCM hemorrhage rate in the pediatric population and provides adequate seizure control

Stereotactic radiosurgery versus active surveillance for incidental, convexity meningiomas: a matched cohort analysis from the IMPASSE study

Background The optimal treatment strategy of asymptomatic, convexity meningiomas, remains unclear. Objective The purpose of this study was to define the safety and efficacy of stereotactic radiosurgery (SRS) in the management of patients with asymptomatic convexity meningiomas. Methods Data of SRS-treated patients from 14 participating centers and patients managed conservatively for an asymptomatic, convexity-located meningioma were compared. Local tumor control rate and development of new neurologic deficits were evaluated in the active surveillance and in the SRS-treated cohorts. Results In the unmatched cohorts, there were 99 SRS-treated patients and 140 patients managed conservatively for an asymptomatic, convexity meningioma. Following propensity score matching for age, there were 98 patients in each cohort. In the matched cohorts, tumor control was achieved in 99% of SRS-treated, and in 69.4% of conservatively managed patients (p < 0.001). New neurological deficits occurred in 2.0% of patients in each of the matched cohorts (p = 1.00). Increasing age was predictive of tumor growth [(OR 1.1; 95% CI (1.04 - 1.2), (p < 0.001)]. Conclusion This is one of the first reports to suggest that SRS is a low risk and effective treatment strategy for asymptomatic incidentally discovered convexity meningiomas. In this study, tumor control was achieved in significantly more patients after radiosurgery compared to those managed with active surveillance. SRS may be offered at diagnosis of an asymptomatic convexity meningioma and should be recommended when meningioma growth is noted on follow-up

Stereotactic radiosurgery versus active surveillance for asymptomatic, skull-based meningiomas: an international, multicenter matched cohort study

The optimal management of asymptomatic, skull-based meningiomas is not well defined. The aim of this study is to compare the imaging and clinical outcomes of patients with asymptomatic, skull-based meningiomas managed either with upfront stereotactic radiosurgery (SRS) or active surveillance. This retrospective, multicenter study involved patients with asymptomatic, skull-based meningiomas. The study end-points included local tumor control and the development of new neurological deficits attributable to the tumor. Factors associated with tumor progression and neurological morbidity were also analyzed. The combined unmatched cohort included 417 patients. Following propensity score matching for age, tumor volume, and follow-up 110 patients remained in each cohort. Tumor control was achieved in 98.2% and 61.8% of the SRS and active surveillance cohorts, respectively. SRS was associated with superior local tumor control (p < 0.001, HR = 0.01, 95% CI = 0.002-0.13) compared to active surveillance. Three patients (2.7%) in the SRS cohort and six (5.5%) in the active surveillance cohort exhibited neurological deterioration. One (0.9%) patient in the SRS-treated and 11 (10%) patients in the active surveillance cohort required surgical management of their meningioma during follow-up. SRS is associated with superior local control of asymptomatic, skull-based meningiomas as compared to active surveillance and does so with low morbidity rates. SRS should be offered as an alternative to active surveillance as the initial management of asymptomatic skull base meningiomas. Active surveillance policies do not currently specify the optimal time to intervention when meningioma growth is noted. Our results indicate that if active surveillance is the initial management of choice, SRS should be recommended when radiologic tumor progression is noted and prior to clinical progression