Aortomonoiliac Endografting after Failed Endovascular Aneurysm Repair: Indications and Long-term Results

AbstractObjectivesTo present long-term results of endoleak/endograft migration treatment by aortomonoiliac (AMI) endografting after failed endovascular aneurysm repair (EVAR) of infrarenal abdominal aortic aneurysms.DesignPost hoc analysis of a prospectively gathered database at a tertiary care university hospital.Materials and methodsFrom March 1995 to November 2010, 23 patients were identified who underwent modification into AMI configuration after failed elective EVAR. Major causes for modification were type I (with/without endograft migration) or type III endoleaks with aneurysm expansion. An average increase in aneurysm size of 1.6 cm (range: −1.5 to 10.5 cm) since initial aneurysm treatment was observed. Interventional outcomes and long-term results were recorded for analysis.ResultsTechnical success rate of AMI endografting was 95.65% (n = 22). All except two endoleaks could be successfully sealed with this manoeuvre (94.44%). Median time to modification was 5.3 years (interquartile range Q1–Q3: 1.3–9.3 years). No intra-operative conversion to open surgery was necessary and mortality was 0%. Median follow-up was 44 months (interquartile range Q1–Q3: 17–69 months).ConclusionsTreatment of graft-related endoleaks/endograft migration by AMI endografting after failed EVAR represents a safe and feasible procedure. This approach broadens the minimal invasive opportunities of aneurysm treatment, and open surgical conversion may be avoided except in selected patients

Mcl-1 Antisense Therapy Chemosensitizes Human Melanoma in a SCID Mouse Xenotransplantation Model

It is well established that high expression of the antiapoptotic Bcl-2 family proteins Bcl-2 and Bcl-xL can significantly contribute to chemoresistance in a number of human malignancies. Much less is known about the role the more recently described Bcl-2 family member Mcl-1 might play in tumor biology and resistance to chemotherapy. Using an antisense strategy, we here address this issue in melanoma, a paradigm of a treatment-resistant malignancy. After in vitro proof of principle supporting an antisense mechanism of action with specific reduction of Mcl-1 protein as a consequence of nuclear uptake of the Mcl-1 antisense oligonucleotides employed, antisense and universal control oligonucleotides were administered systemically in combination with dacarbazine in a human melanoma SCID mouse xenotransplantation model. Dacarbazine, available now for more than three decades, still remains the most active single agent for treatment of advanced melanoma. Mcl-1 antisense oligonucleotides specifically reduced target protein expression as well as the apoptotic threshold of melanoma xenotransplants. Combined Mcl-1 antisense oligonucleotide plus dacarbazine treatment resulted in enhanced tumor cell apoptosis and led to a significantly reduced mean tumor weight (mean 0.16 g, 95% confidence interval 0.08–0.26) compared to the tumor weight in universal control oligonucleotide plus dacarbazine treated animals (mean 0.35 g, 95% confidence interval 0.2–0.44) or saline plus dacarbazine treated animals (mean 0.39 g, 95% confidence interval 0.25–0.53). We thus show that Mcl-1 is an important factor contributing to the chemoresistance of human melanoma in vivo. Antisense therapy against the Mcl-1 gene product, possibly in combination with antisense strategies targeting other antiapoptotic Bcl-2 family members, appears to be a rational and promising approach to help overcome treatment resistance of malignant melanoma

Fertility-sparing treatment for intramucous, moderately differentiated, endometrioid endometrial cancer: A gynecologic cancer inter-group (GCIG) study

Objective: ‘The Endometrial Cancer Conservative Treatment (E.C.Co.). A multicentre archive’ is a worldwide project endorsed by the Gynecologic Cancer Inter-Group, aimed at registering conservatively treated endometrial cancer (EC) patients. This paper reports the oncological and reproductive outcomes of intramucous, G2, endometrioid EC patients from this archive. Methods: Twenty-three patients (Stage IA, G2, endometrioid EC) were enrolled between January 2004 and March 2019. Primary and secondary endpoints were, respectively, complete regression (CR) and recurrence rates, and pregnancy and live birth rates. Results: A median follow-up of 35 months (9–148) was achieved. Hysteroscopic resection (HR) plus progestin was adopted in 74% (17/23) of cases. Seventeen patients showed CR (median time to CR, 6 months; 3-13). Among the 6 non-responders, one showed persistence and 5 progressed, all submitted to definitive surgery, with an unfavorauble outcome in one. The recurrence rate was 41.1%. Ten (58.8%) complete responders attempted to conceive, of whom 3 achieved at least one pregnancy with a live-birth. Two out of the 11 candidate patients underwent definitive surgery, while the remaining 9 have so far refused. To date, 22 patients show no evidence of disease, and one is still alive with disease. Conclusions: Fertility-sparing treatment seems to be feasible even in G2 EC, although caution should be kept considering the potential pathological undergrading or non-endometrioid histology misdiagnosis. The low rate of attempt to conceive and of compliance to definitive surgery underline the need for a ‘global’ counselling extended to the follow-up period

The prognostic value of estrogen receptor beta and proline-, glutamic acid- and leucine-rich protein 1 (PELP1) expression in ovarian cancer

Background: Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), a coregulator of the estrogen receptors (ERs) alpha and beta, is a potential proto-oncogene in hormone dependent gynecological malignancies. To better understand the role of PELP1 in epithelial ovarian cancer (EOC), the protein expression and prognostic significance of PELP1 was evaluated together with ERalpha and ERbeta in EOC tissues. Methods: The expression of PELP1, ERalpha, and ERbeta was characterized in tumor tissues of 63 EOC patients. The prognostic value was calculated performing log-rank tests and multivariate Cox-Regression analysis. In a second step, validation analysis in an independent set of 86 serous EOC patients was performed. Results: Nuclear PELP1 expression was present in 76.2% of the samples. Prevalence of PELP1 expression in mucinous tumors was significantly lower (37.5%) compared to serous (85.7%) and endometrioid tumors (86.7%). A significant association between PELP1 expression and nuclear ERbeta staining was found (p=0.01). Positive PELP1 expression was associated with better disease-free survival (DFS) (p=0.004) and overall survival (OS) (p=0.04). The combined expression of ERbeta+/PELP1+ revealed an independent association with better DFS (HR 0.3 [0.1-0.7], p=0.004) and OS (HR 0.3 [0.1-0.7], p=0.005). In the validation set, the combined expression of ERbeta+/PELP1+ was not associated with DFS (HR 0.7 [0.4-1.3], p=0.3) and OS (HR 0.7 [0.3-1.4], p=0.3). Conclusion: Positive immunohistochemical staining for the ER coregulator PELP1, alone and in combination with ERbeta, might be of prognostic relevance in EOC.Stefanie Aust, Peter Horak, Dietmar Pils, Sophie Pils, Christoph Grimm, Reinhard Horvat, Dan Tong, Bernd Schmid, Paul Speiser, Alexander Reinthaller, and Stephan Polteraue

Clinical significance of preoperative serum interleukin-6 and C-reactive protein level in breast cancer patients

<p>Abstract</p> <p>Background</p> <p>Breast cancer is a disease that continues to plague females during their entire lifetime. IL-6 and CRP are found to be elevated in various inflammatory and malignant diseases and their levels are found to correlate with the extent of the disease. The primary objective of this study was to determine the preoperative serum levels of IL-6 and CRP in breast carcinoma, and to correlate them with the staging of the disease and the prognosis.</p> <p>Methods</p> <p>59 female patients admitted for breast cancer were identified for the study and were subjected to thorough evaluation. Serum levels of IL-6 were assessed via Enzyme-Linked Immuno-Sorbent Assay (ELISA), and CRP was measured via immunoturbidimetry. Histological findings included tumour size, lymph node (LN) metastasis, and tumour staging. Relevant investigations were made to find out the presence of distant metastasis. Statistical analysis of the data was then processed.</p> <p>Results</p> <p>Increases in cancer invasion and staging are generally associated with increases in preoperative serum IL-6 levels. IL-6 and CRP levels correlated with LN metastasis (P < 0.001, P < 0.001) and TNM stage (P < 0.001, P < 0.001). Tumour invasion and the presence of distant metastasis is associated with higher IL-6 levels (P = 0.001, P = 0.009). When we established the cutoff value for IL-6 level (20.55 pg/dl) by ROC curve, we noted a significant difference in overall survival (OS; P = 0.008). However, CRP evidenced no significance with regard to patient's OS levels. Serum IL-6 levels were correlated positively with CRP levels (r2 = 0.579, P < 0.01)</p> <p>Conclusion</p> <p>Serum levels of IL-6 correlates well with the extent of tumor invasion, LN metastasis, distant metastasis and TNM staging thus enveloping all aspects of breast cancer.</p

Circulating fibrinogen is a prognostic and predictive biomarker in malignant pleural mesothelioma.

Background:To investigate the clinical utility of pretreatment plasma fibrinogen levels in malignant pleural mesothelioma (MPM) patients.Methods:A retrospective multicenter study was performed in histologically proven MPM patients. All fibrinogen levels were measured at the time of diagnosis and clinical data were retrospectively collected after approval of the corresponding ethics committees.Results:In total, 176 MPM patients (mean age: 63.5 years+/-10.4 years, 38 females and 138 males) were analysed. Most patients (n=154, 87.5%) had elevated (>/=390 mg dl-1) plasma fibrinogen levels. When patients were grouped by median fibrinogen, patients with low level (</=627 mg dl-1) had significantly longer overall survival (OS) (19.1 months, confidence interval (CI) 14.5-23.7 months) when compared with those with high level (OS 8.5; CI 6.2-10.7 months). In multivariate survival analyses, fibrinogen was found to be an independent prognostic factor (hazard ratio 1.81, CI 1.23-2.65). Most interestingly, fibrinogen (cutoff 75th percentile per 750 mg dl-1) proved to be a predictive biomarker indicating treatment benefit achieved by surgery within multimodality therapy (interaction term: P=0.034). Accordingly, only patients below the 75th percentile benefit from surgery within multimodality therapy (31.3 vs 5.3 months OS).Conclusions:Fibrinogen is a novel independent prognostic biomarker in MPM. Most importantly, fibrinogen predicted treatment benefit achieved by surgery within multimodality therapy.British Journal of Cancer advance online publication, 16 January 2014; doi:10.1038/bjc.2013.815 www.bjcancer.com

Prognostic value of circulating tumor cells and disseminated tumor cells in patients with ovarian cancer: a systematic review and meta-analysis

Recent studies have shown diagnostic and prognostic values of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) in various cancers, including ovarian cancer. We aimed to evaluate the association of CTCs and/or DTCs with the clinical outcomes of ovarian cancer. Clinical studies of CTCs/DTCs of ovarian cancer were included for systematic review and meta-analysis. A total of 236 studies were screened but only 16 qualified studies with 1623 subjects were included. Odds ratio (OR) showed CTCs/DTCs were not significantly associated with serous carcinoma (OR = 0.71 [0.49, 1.05]), lymph node metastasis (OR 1.14 [0.67, 1.93]), and residual disease (OR 1.45 [0.90, 2.34]); but significantly associated with advanced tumor staging (OR = 1.90 [1.02, 3.56]). The overall pooled hazard ratio (HR) of CTCs/DTCs on OS and PFS/DFS was 1.94 [1.56– 2.40] and 1.99 [1.59–2.50], respectively. Subgroup analyses revealed that CTCs were significantly associated OS (HR 1.97 [1.50-2.58]) and PFS/DFS (HR 2.52 [1.83-3.48]), while DTCs was significantly associated OS (HR 1.89 [1.33, 2.68]) and PFS/DFS (HR 1.60 [1.17, 2.19]). Meta-analysis showed strong relationship of CTCs/DTCs with advanced staging, treatment response and poor prognosis in patients with ovarian cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13048-015-0168-9) contains supplementary material, which is available to authorized users

A switching nonlinear MPC approach for ecodriving

In recent years many works focusing on improved vehicle fuel efficiency through advanced control have been carried out, reflecting the high interest in ecodriving of vehicles. Although many studies have shown the potential that optimal control based ecodriving can offer, these solution are often difficult to be translated into online control strategies, one of the reasons being the complexity of the optimal control problem and therefore the computational burden. To cope with this a novel online approach, based on switching Nonlinear Model Predictive Control (NMPC), is proposed. The NMPC strategy is developed for the case of conventional vehicles, where gear shifting and longitudinal dynamics are controlled. It is shown that our proposal can operate in real time, while recovering most of the performance achievable by an offline optimal solution. The development of the method is described in detail and its performance is analyzed. The results show that the proposed NMPC can successfully solve the ecodriving task and seems a good compromise between computational burden and performance suitable for field implementation