Transcatheter and surgical aortic valve replacement in patients with bicuspid aortic valve

Objectives: To compare the outcomes after surgical (SAVR) and transcatheter aortic valve replacement (TAVR) for severe stenosis of bicuspid aortic valve (BAV).Methods: We evaluated the early and mid-term outcome of patients with stenotic BAV who underwent SAVR or TAVR for aortic stenosis from the nationwide FinnValve registry.Results: The FinnValve registry included 6463 AS patients and 1023 (15.8%) of them had BAV. SAVR was performed in 920 patients and TAVR in 103 patients with BAV. In the overall series, device success after TAVR was comparable to SAVR (94.2% vs. 97.1%, p = 0.115). TAVR was associated with increased rate of mild-to-severe paravalvular regurgitation (PVR) (19.4% vs. 7.9%, p < 0.0001) and of moderate-to-severe PVR (2.9% vs. 0.7%, p = 0.053). When newer-generation TAVR devices were evaluated, mild-to-severe PVR (11.9% vs. 7.9%, p = 0.223) and moderate-to-severe PVR (0% vs. 0.7%, p = 1.000) were comparable to SAVR. Type 1 N-L and type 2 L-R/R-N were the BAV morphologies with higher incidence of mild-to-severe PVR (37.5% and 100%, adjusted for new-generation prostheses p = 0.025) compared to other types of BAVs. Among 75 propensity score-matched cohorts, 30-day mortality was 1.3% after TAVR and 5.3% after SAVR (p = 0.375), and 2-year mortality was 9.7% after TAVR and 18.7% after SAVR (p = 0.268) CONCLUSIONS: In patients with stenotic BAV, TAVR seems to achieve early and mid-term results comparable to SAVR. Type 1 N-L and type 2 L-R/R-N BAV morphologies had higher incidence of PVR. Larger studies evaluating different phenotypes of BAV are needed to confirm these findings.</p

Vascular endothelial growth factor-C expression and its relationship to pelvic lymph node status in invasive cervical cancer

Vascular endothelial growth factor-C (VEGF-C) has been implicated in lymphangiogenesis, the process of new lymphatics formation. The present study investigated VEGF-C mRNA expression in invasive cervical cancer tissue. Additionally, the association of VEGF-C mRNA with clinicopathological features was examined. VEGF-C mRNA expression was assessed by reverse transcription-polymerase chain reaction using β-action as an internal control. 75 patients presenting with invasive cervical cancer were included in the trial. VEGF-C mRNA expression was markedly higher in tumours in which pelvic lymph node metastasis was diagnosed by magnetic resonance (MR) imaging (P = 0.002). 53 patients displaying stage Ib–IIb cervical cancer underwent radical hysterectomy and pelvic lymphadenectomy. VEGF-C expression was significantly higher in tumours exhibiting deep stromal invasion, pelvic lymph node metastasis and lymph-vascular space involvement (P = 0.016, P = 0.006 and P = 0.036, respectively). Multivariate analysis revealed VEGF-C mRNA expression to be the sole independent factor influencing pelvic lymph node metastasis. Subjects demonstrating VEGF-C mRNA expression displayed significantly poorer prognoses than those lacking VEGF-C mRNA expression (P = 0.049). These findings provide evidence supporting the involvement of VEGF-C expression in the promotion of lymph node metastasis in cervical cancer. Furthermore, examination of VEGF-C expression in biopsy specimens may be beneficial in the prediction of pelvic lymph node metastasis. © 2001 Cancer Research Campaign http://www.bjcancer.co

Long-Term Survival After Transhiatal Versus Transthoracic Esophagectomy: A Population-Based Nationwide Study in Finland

Background No population-based studies comparing long-term survival after transhiatal esophagectomy (THE) and transthoracic esophagectomy (TTE) exist. This study aimed to compare the 5-year survival of esophageal cancer patients undergoing THE or TTE in a population-based nationwide setting. Methods This study included all curatively intended THE and TTE for esophageal cancer in Finland during 1987-2016, with follow-up evaluation until 31 December 2019. Cox proportional hazard models provided hazard ratios (HRs) with 95% confidence intervals (CIs) of 5-year and 90-day mortality. The results were adjusted for age, sex, year of operation, comorbidities, histology, neoadjuvant treatment, and pathologic stage. Results A total of 1338 patients underwent THE (n = 323) or TTE (n = 1015). The observed 5-year survival rate was 39.3% after THE and 45.0% after TTE (p = 0.072). In adjusted model 1, THE was not associated with greater 5-year mortality (HR 0.99; 95% CI 0.82-1.20) than TTE. In adjusted model 2, including T stage instead of pathologic stage, the 5-year mortality hazard rates after THE (HR 0.87, 95% CI 0.72-1.05) and TTE were comparable. The 90-day mortality rate for THE was higher than for TTE (adjusted HR 0.72; 95% CI 0.45-1.14). In subgroup analyses, no differences between THE and TTE were observed in Siewert II gastroesophageal junction cancers, esophageal cancers, or pN0 tumors, nor in the comparison of THE and TTE with two-field lymphadenectomy. The sensitivity analysis, including patients with missing patient records, who underwent surgery during 1996-2016 mirrored the main analysis. Conclusions This Finnish population-based nationwide study suggests no difference in 5-year or 90-day mortality after THE and TTE for esophageal cancer.</p

CD34+ cell mobilization, blood graft composition, and posttransplant recovery in myeloma patients compared to non‐Hodgkinʼs lymphoma patients: results of the prospective multicenter GOA study

BACKGROUNDAutologous stem cell transplantation is an established treatment option for patients with multiple myeloma (MM) or non‐Hodgkinʼs lymphoma (NHL).STUDY DESIGN AND METHODSIn this prospective multicenter study, 147 patients with MM were compared with 136 patients with NHL regarding the mobilization and apheresis of blood CD34+ cells, cellular composition of infused blood grafts, posttransplant recovery, and outcome.RESULTSMultiple myeloma patients mobilized CD34+ cells more effectively (6.3 × 106/kg vs. 3.9 × 106/kg, p = 0.001). The proportion of poor mobilizers (peak blood CD34+ cell count 100 days) nonrelapse mortality (NRM; 6% vs. 0%, p = 0.003).CONCLUSIONSNon‐Hodgkinʼs lymphoma and MM patients differ in terms of mobilization of CD34+ cells, graft cellular composition, and posttransplant recovery. Thus, the optimal graft characteristics may also be different.</p

Vascular density and phenotype around ductal carcinoma in situ (DCIS) of the breast

Up to 50% of recurrences of ductal carcinoma in situ of the breast are associated with invasive carcinoma but no pathological or molecular features have yet been found to predict for the development of invasive disease. For a tumour to invade, it requires the formation of new blood vessels. Previous studies have described a vascular rim around ducts involved by ductal carcinoma in situ, raising the possibility that the characteristics of periductal vascularisation may be important in determining transformation from in situ to invasive disease. Periductal vascular density and phenotype were determined using morphometry and a panel of anti-endothelial antibodies (von Willebrand factor, CD31, CD141 and CD34) and related to the presence of invasive carcinoma and other histological features. Compared to normal lobules, pure ductal carcinoma in situ exhibited a greater density of CD34+ and CD31+ vessels but a decrease in those that were immunopositive for vWF, indicating a difference in phenotype and in density. Ductal carcinoma in situ associated with invasive carcinoma showed a profile of vascular immunostaining similar to that of pure ductal carcinoma in situ but there were significantly greater numbers of CD34+ and CD141+ vessels and fewer staining for vWF. There was a significant negative correlation between vascular density and both the cross-sectional areas of the ducts involved and the extent of the necrosis of the tumour they contained. A correlation between vascular density and nuclear grade was also noted, being highest in the intermediate grade. The greater density of CD34+ and CD141+ vessels around ductal carcinoma in situ associated with invasive carcinoma could reflect a greater predisposition to invade but a direct effect of co-existent invasive carcinoma cannot entirely be ruled out in the present study. The relationship between vascular density, grade, duct size and nuclear grade suggests that periductal angiogenesis increases with tumour growth rate but is unable to keep pace with the most rapidly growing lesions

Development of Second-Generation VEGFR Tyrosine Kinase Inhibitors: Current Status

The vascular endothelial growth factor (VEGF) signaling pathway appears to be the dominant pathway involved in tumor angiogenesis, providing a rationale for targeting the VEGF receptors (VEGFR-1, -2, and -3) in the treatment of cancers. In particular, VEGF signaling is thought to be important in renal cell carcinoma (RCC) because of the deregulation of the pathway through nearly uniform loss of the von Hippel Lindau protein. The tyrosine kinase inhibitors (TKIs) sorafenib, sunitinib, and pazopanib are approved by the US Food and Drug Administration for the treatment of advanced RCC; however, these multitargeted agents inhibit a wide range of kinase targets in addition to the VEGFRs, resulting in a range of adverse effects unrelated to efficient VEGF blockade. This article reviews recent advances in the development of the second-generation VEGFR TKIs, including the more selective VEGFR TKIs tivozanib and axitinib, and focuses on the potential benefits of novel inhibitors with improved potency and selectivity

Blood Transfusion and Outcome After Transfemoral Transcatheter Aortic Valve Replacement

Objective: To investigate the prognostic impact of red blood cell (RBC) transfusion on the outcome after transfemoral transcatheter aortic valve replacement (TAVR).Design: Nationwide, retrospective multicenter study.Setting: Five University Hospitals.Participants: The nationwide FinnValve registry included data from 2,130 patients who underwent TAVR for aortic stenosis from 2008 to 2017. After excluding patients who underwent TAVR through nontransfemoral accesses, 1,818 patients were selected for this analysis.Intervention: TAVR with or without coronary revascularization.Measurements and Main Results: RBCs were transfused in 293 patients (16.1%). Time-trend analysis showed that the rates of RBC transfusion decreased significantly from 27.5% in 2012 to 10.0% in 2017 (p Conclusions: Patients who received blood transfusion after TAVR had an increased risk of early and late adverse events. These adverse effects were particularly evident with increasing amount of RBC transfusion and operations for excessive bleeding.</p

Mid-term outcomes of Sapien 3 versus Perimount Magna Ease for treatment of severe aortic stenosis

Background: There is limited information on the longer-term outcome after transcatheter aortic valve replacement (TAVR) with new-generation prostheses compared to surgical aortic valve replacement (SAVR). The aim of this study was to compare the mid-term outcomes after TAVR with Sapien 3 and SAVR with Perimount Magna Ease bioprostheses for severe aortic stenosis.Methods: In a retrospective study, we included patients who underwent transfemoral TAVR with Sapien 3 or SAVR with Perimount Magna Ease bioprosthesis between January 2008 and October 2017 from the nationwide FinnValve registry. Propensity score matching was performed to adjust for differences in the baseline characteristics. The Kaplan-Meir method was used to estimate late mortality.Results: A total of 2000 patients were included (689 in the TAVR cohort and 1311 in the SAVR cohort). Propensity score matching resulted in 308 pairs (STS score, TAVR 3.52.2% vs. SAVR 3.52.8%, p=0.918). In-hospital mortality was 3.6% after SAVR and 1.3% after TAVR (p=0.092). Stroke, acute kidney injury, bleeding and atrial fibrillation were significantly more frequent after SAVR, but higher rate of vascular complications was observed after TAVR. The cumulative incidence of permanent pacemaker implantation at 4years was 13.9% in the TAVR group and 6.9% in the SAVR group (p=0.0004). At 4-years, all-cause mortality was 20.6% for SAVR and 25.9% for TAVR (p=0.910). Four-year rates of coronary revascularization, prosthetic valve endocarditis and repeat aortic valve intervention were similar between matched cohorts.Conclusions: The Sapien 3 bioprosthesis achieves comparable midterm outcomes to a surgical bioprosthesis with proven durability such as the Perimount Magna Ease. However, the Sapien 3 bioprosthesis was associated with better early outcome.Trial registration: ClinicalTrials.gov Identifier: NCT03385915.</div