Serum ferritin levels in previously untreated classical Hodgkin lymphoma: correlations and prognostic significance.

Serum ferritin (SF) is frequently elevated in classical Hodgkin lymphoma (cHL). We report on its prognostic significance in an unselected series of 529 cHL patients treated with state-of-the-art therapy. Higher baseline levels correlated with markers of advanced/aggressive disease. SF levels were significantly higher in male and older patients, those with high body mass index and mixed cellularity histology. The strongest correlation was recorded between SF and complement reactive protein (CRP) levels. Gender-specific SF cutoffs which provided the best discrimination in terms of freedom from progression (FFP) were identified. In multivariate analysis elevated SF levels, advanced stage and high lactate dehydrogenase (LDH) were independent prognostic factors of inferior FFP. SF also appears to retain independent prognostic significance for progression-free survival (PFS) but not for overall survival (OS). In conclusion, SF levels in cHL reflect disease activity and are associated with adverse patient outcomes.

Balloon Angioplasty Versus Stenting for the Treatment of Failing Arteriovenous Grafts: A Meta-Analysis.

PURPOSE: To assess the outcomes of plain balloon angioplasty versus stenting for the treatment of failed or malfunctioning chronic haemodialysis arteriovenous grafts (AVGs). METHODS: A systematic search of the literature was undertaken using the PUBMED, EMBASE, and Cochrane databases from January 2000 to September 2016 for articles comparing balloon angioplasty versus stenting in the management of failed or malfunctioning chronic haemodialysis AVGs. Results are reported as OR and 95% CI. RESULTS: The search identified eight studies (1051 patients). Balloon angioplasty alone was used in 521 patients (49.6%) and stenting in 530 patients (50.4%). At the time of the endovascular re-intervention, the mean life of AVGs was 807.7±115.4 days for the balloon angioplasty and 714.2±96.3 days for the stenting group (p=.92). All AVGs were located in the arm. Most procedures (98.1%) were performed across the venous anastomosis, while 88% of the patients in the stenting group received a stent graft. The technical success rate was significantly higher in the stenting group (OR 0.16, 95% CI 0.08-0.31, p<.001). At 12 months, loss of primary and secondary patency was significantly higher in patients undergoing plain balloon angioplasty compared with stenting (OR 3.54, 95% CI 2.18-5.74, p<.001, and OR 1.82, 95% 1.17-2.82, p=.008, respectively). CONCLUSION: Stenting is associated with better technical success and patency rates compared with plain angioplasty in treating failed or malfunctioning chronic haemodialysis AVGs, and thus it should be considered as the first line therapeutic option.

Acute limb ischemia and anticoagulation in patients with history of atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the commonest source of arterial embolization causing acute limb ischemia (ALI). The aim of this study was to assess the adherence of anticoagulation in AF patients and the treatment of underdiagnosed AF patients, presenting with ALI in our service and to evaluate the risk factors associated with morbidity and mortality. METHODS: A retrospective analysis of prospectively collected data was carried out from 115 limbs of 112 consecutive patients presenting with ALI of AF origin from 2008 until 2012 to a tertiary vascular service. RESULTS: The mean transfer time to hospital was 12±8.5 h. On admission, only half of the patients were aware of having AF and only 67% of those patients were receiving oral anticoagulants at the time of their admission. Nearly all patients who were on Vitamin K Antagonists (VKA) had sub-therapeutic levels preoperatively on admission (92%). The 30-day postoperative mortality and morbidity rates were 1.7% and 47% respectively. The lower limb amputation rate was 4.4% and was only associated with diabetes mellitus (DM) (P=0.009553). Reversible renal impairment was correlated with increased creatinine phosphokinase (CPK) blood levels on admission (P=0.038). CONCLUSIONS: A considerable number of patients with AF might still remain without proper anticoagulation. DM increases the risk of lower limb loss after ALI. Development of renal impairment after thromboembolectomy for ALI is more likely in the presence of elevated CPK blood levels on admission.

Association between carotid artery occlusion and ultrasonographic plaque type.

BACKGROUND: Internal carotid artery (ICA) occlusion is associated with acute stroke and carries significant morbidity and mortality. The aim of this study was to examine whether ultrasonographic carotid plaque type may be associated with ICA occlusion. METHODS: Two hundred eleven patients (85% men, mean age 66.0±9.5 years, 28.9% asymptomatic) with ICA occlusion were included in this case-control study. Ultrasonographic Gray-Weale plaque type (I-IV, echolucent to echogenic) characterization was obtained in both the occluded and the contralateral ICA. Univariate and conditional logistic regression analyses with 1:1 pair matching per artery were undertaken. Each contralateral carotid artery with stenosis was treated as control to the ipsilateral-occluded ICA of the same patient. RESULTS: A total of 261 ICAs (61.9%) were recorded with type I-II plaque, of which 165 (63.2%) were among the occluded and 96 (36.8%) were among the contralateral ICAs with stenosis (P<0.001). Mean contralateral ICA stenosis was 58.2%±20.4%. Regression analysis showed that carotid plaque type I-II was significantly associated with carotid artery occlusion compared with plaque type III-IV (crude odds ratio [OR]=4.29, 95% confidence intervals [CI]=2.81-6.57%, P<0.001, adjusted OR=5.60, 95% CI=3.23-9.70, P<0.001). Previous neurological events did not seem to be significantly associated with plaque echolucency (OR=0.62, 95% CI=0.29-1.35, P=0.23). CONCLUSIONS: A significant association between echolucent plaque and ICA occlusion was observed. This observational hypothesis may prompt for further investigation of the causal mechanism between carotid plaque type and ICA occlusion by larger cohort studies.

Expression and prognostic significance of cyclin D3 in ovarian adenocarcinomas.

Abnormal expression of cell cycle regulators may contribute to malignant transformation. However, the clinical significance of the expression of cyclin D3 in ovarian cancer remains undefined. We therefore conducted a retrospective investigation to address the role of this cell-cycle protein in this tumor. In our study, paraffin-embedded tissue from 109 nonbenign epithelial ovarian tumors, including 17 tumors of low malignant potential and 92 primary adenocarcinomas, was stained immunohistochemically for cyclin D3. Most of the cases had previously been stained for pRb, p21Cip1, p27Kip1, p53, and Ki-67 antigen. Expression of cyclin D3 was correlated with clinicopathologic features, the expression of other cell cycle regulators, and postoperative survival of patients. Cyclin D3 levels were significantly higher in tumors of low malignant potential than in adenocarcinomas (P = 0.0002). In the latter group, cyclin D3 expression decreased with increasing grade (P = 0.0004) and advancing stage (P = 0.0315). Cyclin D3 expression positively correlated with pRb, p21Cip1, and p27Kip1 levels (P = 0.0021; P = 0.0036; P < 0.0001, respectively) and negatively with p53 and Ki-67 (P = 0.0003; P < 0.0001). Absent cyclin D3 expression was an important indicator of poor survival in univariate analysis in the entire cohort (P > 0.00010) and in the platinum-treated patients (P = 0.001) and in multivariate analysis (P = 0.044). Our results demonstrate that absent or decreased cyclin D3 expression is adversely related to several clinicopathologic indicators of aggressiveness in ovarian adenocarcinomas and is combined with a better prognosis, suggesting that cyclin D3 may have a biological role distinct from that of other G1 cyclins which is possibly regulated through interaction with other cell cycle genes.

Reduced retinoblastoma gene protein to Ki-67 ratio is an adverse prognostic indicator for ovarian adenocarcinoma patients.

OBJECTIVE: Alterations in the retinoblastoma gene (RB-1) are common in human neoplasia. However, the clinical significance of the deregulated expression of RB-1 in ovarian cancer remains undefined. We therefore conducted a retrospective investigation to clarify the relationships of RB-1 gene protein (pRb) to the percentage of cycling cells, clinicopathologic variables, other G1 interacting proteins and prognosis of nonbenign epithelial ovarian tumors. METHODS: Paraffin-embedded tissue from 127 nonbenign epithelial ovarian tumors, including 44 of low malignant potential (LMP) and 83 primary ovarian adenocarcinomas, was stained immunohistochemically for pRb, p21(Cip1), p27(Kip1), p53, and Ki-67 antigen (a cell proliferation associated marker). Expression of these markers was correlated with clinicopathologic features and with overall survival of patients with adenocarcinomas. RESULTS: pRb levels were significantly lower in LMP tumors than in carcinomas (P = 0.027). In the latter group, pRb expression decreased with increasing grade (I-II vs III) (P = 0.010), advancing stage (I-II vs III) (P < 0.001), and bulk residual disease (P = 0.014). pRb was not related to Ki-67 expression (P > 0.10) or to overall survival (P > 0.10) but a low pRb to Ki-67 ratio emerged as an important indicator of poor survival in univariate analysis in the entire cohort (P = 0.0076) and in the platinum-treated patients (P = 0.0162) as well as in multivariate analysis, along with histologic type and FIGO stage. CONCLUSIONS: Diminished pRb levels are related to several clinicopathologic indicators of aggressiveness in ovarian adenocarcinomas. More importantly, pRb expression coupled with the percentage of Ki-67 positive cells is a better prognostic marker than pRb, Ki-67, or other G1 interacting proteins and supplements the information gained from traditional prognosticators.

The combined evaluation of p27Kip1 and Ki-67 expression provides independent information on overall survival of ovarian carcinoma patients.

OBJECTIVE: Considering the limited and controversial information on the significance of the cyclin-dependent kinase inhibitor p27Kip1 in ovarian cancer, we conducted a retrospective investigation to clarify the relationships of this protein to proliferation rate, clinicopathologic variables, and prognosis of epithelial ovarian tumors. METHODS: Paraffin-embedded tissue from 43 ovarian tumors of low malignant potential (LMP) and 80 primary ovarian adenocarcinomas was stained immunohistochemically for p27Kip1, Ki-67 antigen (a marker of cell proliferation), and p53 protein. Expression of these markers was correlated with clinicopathologic features and with overall survival of patients with adenocarcinomas. RESULTS: p27Kip1 levels were significantly higher in LMP tumors as well as in low-grade, early-stage, slowly proliferating adenocarcinomas and those associated with minimal residual disease (P < 0.001). Decreased p27Kip1 expression was related to poor overall survival on its own (P = 0.0304) and, when combined, to increased proliferation rate (P = 0.0232). More importantly, in multivariate analysis, p27Kip1/Ki-67 status was independently related to survival (P = 0.040) along with histologic type and FIGO stage. CONCLUSION: Decreased p27Kip1 expression is related to several clinicopathologic indicators of aggressiveness in ovarian adenocarcinomas and is a major player in cell cycle control in these neoplasms. On the contrary, deregulation of the protein does not seem to participate in the pathogenesis of LMP tumors. Furthermore, combined p27Kip1/Ki-67 expression is a better prognostic marker than expression of p27Kip1 or Ki-67 alone and supplements the prognostic information gained from traditional prognosticators.