Selection of an early biomarker for vascular normalization using dynamic contrast-enhanced ultrasonography to predict outcomes of metastatic patients treated with bevacizumab.

BACKGROUND: Dynamic contrast-enhanced ultrasonography (DCE-US) has been used for evaluation of tumor response to antiangiogenic treatments. The objective of this study was to assess the link between DCE-US data obtained during the first week of treatment and subsequent tumor progression. PATIENTS AND METHODS: Patients treated with antiangiogenic therapies were included in a multicentric prospective study from 2007 to 2010. DCE-US examinations were available at baseline and at day 7. For each examination, a 3 min perfusion curve was recorded just after injection of a contrast agent. Each perfusion curve was modeled with seven parameters. We analyzed the correlation between criteria measured up to day 7 on freedom from progression (FFP). The impact was assessed globally, according to tumor localization and to type of treatment. RESULTS: The median follow-up was 20 months. The mean transit time (MTT) evaluated at day 7 was the only criterion significantly associated with FFP (P = 0.002). The cut-off point maximizing the difference between FFP curves was 12 s. Patients with at least a 12 s MTT had a better FFP. The results according to tumor type were significantly heterogeneous: the impact of MTT on FFP was more marked for breast cancer (P = 0.004) and for colon cancer (P = 0.025) than for other tumor types. Similarly, the differences in FFP according to MTT at day 7 were marked (P = 0.004) in patients receiving bevacizumab. CONCLUSION: The MTT evaluated with DCE-US at day 7 is significantly correlated to FFP of patients treated with bevacizumab. This criterion might be linked to vascular normalization. AFSSAPS NO: 2007-A00399-44.

Diagnosis and treatment of pulmonary arteriovenous malformations in hereditary hemorrhagic telangiectasia: An overview.

Hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease is an autosomic dominant disorder, which is characterized by the development of multiple arteriovenous malformations in either the skin, mucous membranes, and/or visceral organs. Pulmonary arteriovenous malformations (PAVMs) may either rupture, and lead to life-threatening hemoptysis/hemothorax or be responsible for a right-to-left shunting leading to paradoxical embolism, causing stroke or cerebral abscess. PAVMs patients should systematically be screened as the spontaneous complication rate is high, by reaching almost 50%. Neurological complications rate is considerably higher in patients presenting with diffuse pulmonary involvement. PAVM diagnosis is mainly based upon transthoracic contrast echocardiography and CT scanner examination. The latter also allows the planification of treatments to adopt, which consists of percutaneous embolization, having replaced surgery in most of the cases. The anchor technique consists of percutaneous coil embolization of the afferent pulmonary arteries of the PAVM, by firstly placing a coil into a small afferent arterial branch closely upstream the PAVM. Enhanced contrast CT scanner is the key follow-up examination that depicts the PAVM enlargement, indicating the various mechanisms of PAVM reperfusion. When performed by experienced operators as the prime treatment, percutaneous embolization of PAVMs, is a safe, efficient and sustained therapy in the great majority of HHT patients.

A G577R mutation in the human AR P box results in selective decreases in DNA binding and in partial androgen insensitivity syndrome.

We have characterized a novel mutation of the human AR, G577R, associated with partial androgen insensitivity syndrome. G577 is the first amino acid of the P box, a region crucial for the selectivity of receptor/DNA interaction. Although the equivalent amino acid in the GR (also Gly) is not involved in DNA interaction, the residue at the same position in the ER (Glu) interacts with the two central base pairs in the PuGGTCA motif. Using a panel of 16 palindromic probes that differ in these base pairs (PuGNNCA) in gel shift experiments with either the AR DNA-binding domain or the full length receptor, we observed that the G577R mutation does not induce binding to probes that are not recognized by the wild-type AR. However, binding to the four PuGNACA elements recognized by the wild-type AR was affected to different degrees, resulting in an altered selectivity of DNA response element recognition. In particular, AR-G577R did not interact with PuGGACA palindromes. Modeling of the complex between mutant AR and PuGNACA motifs indicates that the destabilizing effect of the mutation is attributable to a steric clash between the C beta of Arg at position 1 of the P box and the methyl group of the second thymine residue in the TGTTCPy arm of the palindrome. In addition, the Arg side chain can interact with G or T at the next position (PuGCACA and PuGAACA elements, respectively). The presence of C is not favorable, however, because of incompatible charges, abrogating binding to the PuGGACA element. Transactivation of several natural or synthetic promoters containing PuGGACA motifs was drastically reduced by the G577R mutation. These data suggest that androgen target genes may be differentially affected by the G577R mutation, the first natural mutation characterized that alters the selectivity of the AR/DNA interaction. This type of mutation may thus contribute to the diversity of phenotypes associated with partial androgen insensitivity syndrome.

[Coronary steal syndrome by systemic pulmonary hypervascularization fed by a mammary-left anterior descending artery bypass. Treatment by embolization]. / Vol coronarien par hypervascularisation systémique pulmonaire alimentée par un pontage mammaire--interventriculaire antérieure. Traitement par embolisation.

We report a case of coronary-steal syndrome which occurred after coronary bypass surgery. It was related to systemic hypervascularization of the lung caused by a bronchopathy. The steal syndrome was fed by an ectopic bronchial artery arising from the internal mammary--left anterior descending artery bypass graft. The myocardial ischemia disappeared after hyperselective embolization of the ectopic bronchial artery. The authors outline the rarity of this syndrome and its pathophysiology. They insist on the necessity to perform broncho-systemic arteriography for candidates to coronary surgery, in patients with thoracic diseases which can induce systemic hypervascularization of the lung.

[Intralobar sequestration of the lung in an adult (type 1 of pryce). Treatment by coil embolization]. / Séquestration pulmonaire intralobaire de type pryce 1 chez l'adulte. Vaso-occlusion par spires métalliques.

A 34 year old patient presented with recurrent hemoptysis. A chest radiograph was normal. Helical CT angiogram of the chest with tridimensional reconstructions demonstrated an intralobar pulmonary vascular sequestration Pryce I-type of the right lower lobe. The angiography confirmed the diagnosis showing a large feeding artery arising from the coeliac trunk. An embolization of the feeding artery using metallic coils was performed. Transient pulmonary infarction occurred immediately after treatment. At two years follow-up, the patient remains asymptomatic. Percutaneous embolization of this rare pulmonary vascular malformation is an alternative to surgical treatment.

Implanted central venous catheter-related acute superior vena cava syndrome: management by metallic stent and endovascular repositioning of the catheter tip.

We describe a case of a 49-year-old woman with stage-IIIB lung adenocarcinoma who experienced an acute superior vena cava syndrome related to an implanted central venous catheter without associated venous thrombosis. The catheter was surgically implanted for chemotherapy. Superior vena cava syndrome appeared after the procedure and was due to insertion of the catheter through a subclinical stenosis of the superior vena cava. Complete resolution of the patient's symptoms was obtained using stent placement and endovascular repositioning of the catheter tip.