Ruptured Internal Iliac Artery Aneurysm: Staged Emergency Endovascular Treatment in the Interventional Radiology Suite

Ruptured aneurysms of the internal iliac artery (IIA) are rare and challenging to treat surgically. Due to their anatomic location they are difficult to operate on and perioperative morbidity is high. An endovascular approach can be helpful. We recently treated a patient with a ruptured IIA aneurysm in the interventional radiology suite with embolization of the side-branch of the IIA and placement of a covered stent in the ipsilateral common and external iliac arteries. A suitable stent-graft was not available initially and had to be brought in from elsewhere. An angioplasty balloon was temporarily placed across the ostium of the IIA to obtain hemostasis. Two hours later, the procedure was finished by placing the stent-graft

Reduced BRCA1 expression due to promoter hypermethylation in therapy-related acute myeloid leukaemia

BRCA1 plays a pivotal role in the repair of DNA damage, especially following chemotherapy and ionising radiation. We were interested in the regulation of BRCA1 expression in acute myeloid leukaemia (AML), in particular in therapy-related forms (t-AML). Using real-time PCR and Western blot, we found that BRCA1 mRNA was expressed at barely detectable levels by normal peripheral blood granulocytes, monocytes and lymphocytes, whereas control BM-mononuclear cells and selected CD34+ progenitor cells displayed significantly higher BRCA1 expression (P=0.0003). Acute myeloid leukaemia samples showed heterogeneous BRCA1 mRNA levels, which were lower than those of normal bone marrows (P=0.0001). We found a high frequency of hypermethylation of the BRCA1 promoter region in AML (51/133 samples, 38%), in particular in patients with karyotypic aberrations (P=0.026), and in t-AML, as compared to de novo AML (76 vs 31%, P=0.0002). Examining eight primary tumour samples from hypermethylated t-AML patients, BRCA1 was hypermethylated in three of four breast cancer samples, whereas it was unmethylated in the other four tumours. BRCA1 hypermethylation correlated to reduced BRCA1 mRNA (P=0.0004), and to increased DNA methyltransferase DNMT3A (P=0.003) expression. Our data show that reduced BRCA1 expression owing to promoter hypermethylation is frequent in t-AML and that this could contribute to secondary leukaemogenesis

Novel tumor suppressive function of Smad4 in serum starvation-induced cell death through PAK1–PUMA pathway

DPC4 (deleted in pancreatic cancer 4)/Smad4 is an essential factor in transforming growth factor (TGF)-β signaling and is also known as a frequently mutated tumor suppressor gene in human pancreatic and colon cancer. However, considering the fact that TGF-β can contribute to cancer progression through transcriptional target genes, such as Snail, MMPs, and epithelial–mesenchymal transition (EMT)-related genes, loss of Smad4 in human cancer would be required for obtaining the TGF-β signaling-independent advantage, which should be essential for cancer cell survival. Here, we provide the evidences about novel role of Smad4, serum-deprivation-induced apoptosis. Elimination of serum can obviously increase the Smad4 expression and induces the cell death by p53-independent PUMA induction. Instead, Smad4-deficient cells show the resistance to serum starvation. Induced Smad4 suppresses the PAK1, which promotes the PUMA destabilization. We also found that Siah-1 and pVHL are involved in PAK1 destabilization and PUMA stabilization. In fact, Smad4-expressed cancer tissues not only show the elevated expression of PAK1, but also support our hypothesis that Smad4 induces PUMA-mediated cell death through PAK1 suppression. Our results strongly suggest that loss of Smad4 renders the resistance to serum-deprivation-induced cell death, which is the TGF-β-independent tumor suppressive role of Smad4

Genomic deletion and promoter methylation status of Hypermethylated in Cancer 1 (HIC1) in mantle cell lymphoma

Mantle cell lymphomas (MCL), characterized by the t(11;14)(q13;q32), frequently carry secondary genetic alterations such as deletions in chromosome 17p involving the TP53 locus. Given that the association between TP53-deletions and concurrent mutations of the remaining allele is weak and based on our recent report that the Hypermethylated in Cancer 1 (HIC1) gene, that is located telomeric to the TP53 gene, may be targeted by deletions in 17p in diffuse large B-cell lymphoma (DLBCL), we investigated whether HIC1 inactivations might also occur in MCL. Monoallelic deletions of the TP53 locus were detected in 18 out of 59 MCL (31%), while overexpression of p53 protein occurred in only 8 out of 18 of these MCL (44%). In TP53-deleted MCL, the HIC1 gene locus was co-deleted in 11 out of 18 cases (61%). However, neither TP53 nor HIC1 deletions did affect survival of MCL patients. In most analyzed cases, no hypermethylation of the HIC1 exon 1A promoter was observed (17 out of 20, 85%). However, in MCL cell lines without HIC1-hypermethylation, the mRNA expression levels of HIC1 were nevertheless significantly reduced, when compared to reactive lymph node specimens, pointing to the occurrence of mechanisms other than epigenetic or genetic events for the inactivation of HIC1 in this entity

Extensive use of peripheral angioplasty, particularly infrapopliteal, in the treatment of ischaemic diabetic foot ulcers : clinical results of a multicentric study of 221 consecutive diabetic subjects

OBJECTIVE: To evaluate the feasibility, technical effectiveness and limb salvage potential of percutaneous transluminal angioplasty (PTA), particularly infrapopliteal, in diabetic subjects with ischaemic foot ulcer. DESIGN: Intervention study with PTA in consecutive series. SETTING: Six Diabetology Foot Centres and one Cardiovascular Catheterization Laboratory in Italy. SUBJECTS: Two hundred and twenty-one consecutive diabetic subjects hospitalized for ischaemic foot ulcer. INTERVENTION: Peripheral arterial occlusive disease (PAOD) was investigated by means of foot pulses assessment, ankle-brachial-index (ABI), transcutaneous oxygen tension (TcPO2) and duplex scanning. If non-invasive parameters suggested PAOD, angiography was performed and a PTA was carried out during the same session. MAIN OUTCOME MEASURES: PTA feasibility, improvement of ABI and TcPO2, limb salvage rate, clinical recurrence. RESULTS: On angiography, two patients had stenoses which were 50%, even when longer than 10 cm and/or multiple/calcified. In 11 patients (5.8%) PTA was performed in the proximal axis exclusively, in 81 (42.4%) patients in the infrapopliteal axis exclusively and in 99 (51.8%) in both the femoropopliteal and infrapopliteal axis. Both ABI and TcPO2 improved significantly after PTA (P < 0.0001). Clinical recurrence occurred in 14 subjects: 10 of whom underwent a second successful PTA. Of the 191 patients who underwent PTA, 10 (5.2%) underwent an above-the-ankle amputation. CONCLUSIONS: PTA, including infrapopliteal, is feasible in most diabetic subjects with ischaemic foot ulcer and is effective for foot revascularization. Clinical recurrence was infrequent and the procedure could successfully be repeated in most cases. In subjects treated successfully with PTA the above-the-ankle amputation rate was low. PTA should be considered as the revascularization treatment of first choice in all diabetic subjects with foot ulcer and PAOD

Indications for islet or pancreatic transplantation: Statement of the TREPID working group on behalf of the Societe francophone du diabete (SFD), Societe francaise d'endocrinologie (SFE), Societe francophone de transplantation (SFT) and Societe francaise de nephrologie - dialyse - transplantation (SFNDT)

While either pancreas or pancreatic islet transplantation can restore endogenous insulin secretion in patients with diabetes, no beta-cell replacement strategies are recommended in the literature. For this reason, the aim of this national expert panel statement is to provide information on the different kinds of beta-cell replacement, their benefit-risk ratios and indications for each type of transplantation, according to type of diabetes, its control and association with end-stage renal disease. Allotransplantation requires immunosuppression, a risk that should be weighed against the risks of poor glycaemic control, diabetic lability and severe hypoglycaemia, especially in cases of unawareness. Pancreas transplantation is associated with improvement in diabetic micro- and macro-angiopathy, but has the associated morbidity of major surgery. Islet transplantation is a minimally invasive radiological or mini-surgical procedure involving infusion of purified islets via the hepatic portal vein, but needs to be repeated two or three times to achieve insulin independence and long-term functionality. Simultaneous pancreas-kidney and pancreas after kidney transplantations should be proposed for kidney recipients with type 1 diabetes with no surgical, especially cardiovascular, contraindications. In cases of high surgical risk, islet after or simultaneously with kidney transplantation may be proposed. Pancreas, or more often islet, transplantation alone is appropriate for non-uraemic patients with labile diabetes. Various factors influencing the therapeutic strategy are also detailed in this report. (C) 2018 Published by Elsevier Masson SAS