STABILITY OF ABNORMAL KARYOTYPES IN CELL CULTURE1

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Healing of bronchopleural fistula using a modified Dumon stent: a case report

BACKGROUND: Brochopleural fistula following lung resection is a therapeuric challenge for thoracic surgeons. CASE PRESENTATION: We describe a case of late bronchopleural fistula after right extrapleural pneumonectomy for malignant mesothelioma. Bronchoscopic attempts to repair it were unsuccessful. CONCLUSION: The use of a modified Y Dumon stent associated with glue apposition on the bronchial stump allowed us to close the fistula without the need of any surgical repair

Impact of environmental pollution and weather changes on the incidence of ST-elevation myocardial infarction

Background: Environmental pollution and weather changes unfavorably impact on cardiovascular disease. However, limited research has focused on ST-elevation myocardial infarction (STEMI), the most severe yet distinctive form of acute coronary syndrome. Methods and results: We appraised the impact of environmental and weather changes on the incidence of STEMI, analysing the bivariate and multivariable association between several environmental and atmospheric parameters and the daily incidence of STEMI in two large Italian urban areas. Specifically, we appraised: carbon monoxide (CO), nitrogen dioxide (NO2), nitric oxide (NOX), ozone, particulate matter smaller than 10 μm (PM10) and than 2.5 μm (PM2.5), temperature, atmospheric pressure, humidity and rainfall. A total of 4285 days at risk were appraised, with 3473 cases of STEMI. Specifically, no STEMI occurred in 1920 (44.8%) days, whereas one or more occurred in the remaining 2365 (55.2%) days. Multilevel modelling identified several pollution and weather predictors of STEMI. In particular, concentrations of CO (p=0.024), NOX (p=0.039), ozone (p=0.003), PM10 (p=0.033) and PM2.5 (p=0.042) predicted STEMI as early as three days before the event, as well as subsequently, and NO predicted STEMI one day before (p = 0.010), as well as on the same day. A similar predictive role was evident for temperature and atmospheric pressure (all p < 0.05). Conclusions: The risk of STEMI is strongly associated with pollution and weather features. While causation cannot yet be proven, environmental and weather changes could be exploited to predict STEMI risk in the following days

Capecitabine and bevacizumab as first-line treatment in elderly patients with metastatic colorectal cancer

BACKGROUND: The efficacy and safety of capecitabine and bevacizumab in elderly patients with metastatic colorectal cancer (mCRC) considered unsuitable for receiving first-line chemotherapy with an irinotecan or oxaliplatin-based combination were assessed in a phase II, open, multicentre, uncontrolled study. METHODS: Treatment consisted of capecitabine 1250 mgm 2 (or 950 mgm 2 for patients with a creatinine clearance of 30–50ml min 1) twice daily on days 1–14 and bevacizumab (7.5 mg kg 1) on day 1 every 3 weeks. RESULTS: A total of 59 patients aged X70 years with mCRC were enrolled. In an intention-to-treat analysis, the overall response rate was 34%, with 71% of patients achieving disease control. Median progression-free survival and overall survival were 10.8 months and 18 months, respectively. In all, 32 patients (54%) had grade 3/4 adverse events (AEs), the most common being hand–foot syndrome (19%), diarrhoea (9%) and deep venous thrombosis (7%). Four patients died because of treatment-related AEs. A relationship was detected between creatinine clearance p50 ml min 1 and the development of non-bevacizumab-related grade 3/4 AEs. The incidence of bevacizumab-associated AEs (hypertension, thromboembolic events and proteinuria) was consistent with that of previous reports in elderly patients. CONCLUSION: Bevacizumab combined with capecitabine represents a valid therapeutic alternative in elderly patients considered to be unsuitable for receiving polychemotherapy.This study was supported by Hoffmann-La Roche, Nutley, NJ, USA

ISRCTN12125882 - Influence of topical anti-VEGF (Ranibizumab) on the outcome of filtration surgery for glaucoma - Study Protocol

<p>Abstract</p> <p>Background</p> <p>Excessive wound healing, with scarring of the episcleral tissue or encapsulation of the filtering bleb is the main reason for failure in trabeculectomy. Ranibizumab, an inhibitor of the Vascular Endothelial Growth Factor (VEGF), is seen as a promising candidate to prevent or treat extensive wound healing. We describe the design of a two phased study, i) assessing the local tolerability and safety of topical ranibizumab and ii) assessing the efficacy of topical ranibizumab against placebo in patients who underwent trabeculectomy with mitomycin C combined with phacoemulsification and intra ocular lens (IOL) implantation.</p> <p>Methods/Design</p> <p>In the first phase five patients that had trabeculectomy with mitomycin C combined with phacoemulsification and IOL implantation will be treated with topical ranibizumab (Lucentis^®) eye drops (2 mg/ml) four times daily for one month. The treatment will be started at the first postoperative day. Patients will be assessed for local and systemic side effects using a standardised schedule. In the second phase, after successful completion of phase 1, consenting eligible patients who underwent trabeculectomy with mitomycin C combined with phacoemulsification and IOL implantation will be randomised to either receive topical ranibizumab eye drops (2 mg/ml) four times daily for 1 month or placebo (BSS 4x/d for 1 month). Patients will be reviewed weekly for 4 weeks until conjunctival sutures are removed. Further follow up examinations are planned after 3 and six months. Assessment of differences in the intraocular eye pressure will be considered primary, and bleb appearance/vascularisation using a standardized photography and the Moorfields bleb grading system, postoperative intraocular pressure and conjunctival wound healing problems will be considered secondary outcome parameters.</p> <p>Discussion</p> <p>Anti-VEGF-antibodies might be more effective in preventing scaring and might have fewer toxic side effects than the currently used anti-metabolites and may replace them in the long term.</p> <p>Trial Registration</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN12125882">ISRCTN12125882</a></p

Hedgehog-interacting protein is highly expressed in endothelial cells but down-regulated during angiogenesis and in several human tumors

BACKGROUND: The Hedgehog (Hh) signaling pathway regulates a variety of developmental processes, including vasculogenesis, and can also induce the expression of pro-angiogenic factors in fibroblasts postnatally. Misregulation of the Hh pathway has been implicated in a variety of different types of cancer, including pancreatic and small-cell lung cancer. Recently a putative antagonist of the pathway, Hedgehog-interacting protein (HIP), was identified as a Hh binding protein that is also a target of Hh signaling. We sought to clarify possible roles for HIP in angiogenesis and cancer. METHODS: Inhibition of Hh signaling by HIP was assayed by measuring the induction of Ptc-1 mRNA in TM3 cells treated with conditioned medium containing Sonic hedgehog (Shh). Angiogenesis was assayed in vitro by EC tube formation on Matrigel. Expression of HIP mRNA was assayed in cells and tissues by Q-RT-PCR and Western blot. HIP expression in human tumors or mouse xenograft tumors compared to normal tissues was assayed by Q-RT-PCR or hybridization of RNA probes to a cancer profiling array. RESULTS: We show that Hedgehog-interacting protein (HIP) is abundantly expressed in vascular endothelial cells (EC) but at low or undetectable levels in other cell types. Expression of HIP in mouse epithelial cells attenuated their response to Shh, demonstrating that HIP can antagonize Hh signaling when expressed in the responding cell, and supporting the hypothesis that HIP blocks Hh signaling in EC. HIP expression was significantly reduced in tissues undergoing angiogenesis, including PC3 human prostate cancer and A549 human lung cancer xenograft tumors, as well as in EC undergoing tube formation on Matrigel. HIP expression was also decreased in several human tumors of the liver, lung, stomach, colon and rectum when compared to the corresponding normal tissue. CONCLUSION: These results suggest that reduced expression of HIP, a naturally occurring Hh pathway antagonist, in tumor neo-vasculature may contribute to increased Hh signaling within the tumor and possibly promote angiogenesis

Surgery with curative-intent in patients treated with first-line chemotherapy plus bevacizumab for metastatic colorectal cancer First BEAT and the randomised phase-III NO16966 trial

BACKGROUND: Complete resection of metastases can result in cure for selected patients with metastatic colorectal cancer. METHODS: First BEAT evaluated the safety of bevacizumab with first-line chemotherapy in 1914 patients. Prospectively collected data from 225 patients who underwent curative-intent surgery were analysed, including an exploratory comparison of resection rate in patients treated with different regimens. NO16966 compared efficacy of oxaliplatin-based chemotherapy plus bevacizumab or placebo in 1400 patients. A retrospective analysis of resection rate was undertaken. RESULTS: In First BEAT, 225 out of 1914 patients (11.8%) underwent curative-intent surgery at median 64 days ( range 42-100) after the last dose of bevacizumab. R0 resection was achieved in 173 out of 225 patients (76.9%). There were no surgery-related deaths and serious post-operative complications were uncommon, with grade 3/4 bleeding and wound-healing events reported in 0.4% and 1.8%, respectively. Resection rates were highest in patients receiving oxaliplatin-based combination chemotherapy (P=0.002), possibly confounded by patient selection. In NO16966, 44 out of 699 patients treated with bevacizumab (6.3%) and 34 out of 701 patients treated with placebo (4.9%) underwent R0 metastasectomy (P=0.24). CONCLUSIONS: The rate of serious post-operative complications in First BEAT was comparable to historical controls without bevacizumab. In NO16966, there were no statistically significant differences in resection rates or overall survival in patients treated with bevacizumab vs placebo