L’alpha thalassémie-syndrome myélodysplasique (ATSMD) est une complication possible associée à l’instabilité génétique des hémopathies clonales telles que les syndromes myélodysplasiques (SMD). Cette ...pathologie est caractérisée par la production d’une hémoglobine dite H constituée d’un tétramère de chaînes bêta du fait de l’incapacité à synthétiser des globines alpha.
Un patient de 86 ans avec une anémie chronique et microcytaire non carentielle, aggravait soudainement son anémie avec une anisocytose et une poïkilocytose marquées. L’examen cytologique de la moelle osseuse et le caryotype étaient en faveur d’un SMD avec dysplasie multilignée de bon pronostic. La coloration du sang périphérique au Bleu de Crésyl montrait des hématies « en balle de golf ». L’électrophorèse de l’hémoglobine montrait une hémoglobine H. Le diagnostic d’ATSMD était porté du fait d’une mutation non-sens du gène ATRX mise en évidence au séquençage de nouvelle génération.
L’association SMD, anémie microcytaire avec anisocytose et poïkilocytose doit faire évoquer le diagnostic de ATSMD, qui complique moins de 10 % des SMD.
Alpha thalassemia-myelodysplastic syndrome (ATMDS) is one of the possible complications related to the genetic instability typical of clonal hemopoietic disorders such as myelodysplastic syndromes (MDS). Hemoglobin H acquisition, which is hemoglobin without alpha chains and with 4 beta chains is the hallmark of this disease.
An 86-year-old male with chronic, microcytic anemia was referred due to a fall in his hemoglobin level. The blood smear was remarkable for intense anisocytoses and poikilocytosis. Bone marrow analysis was followed by a diagnosis of MDS with a good prognostic score. Peripheral blood coloration with brilliant cresyl blue showed “golf ball-like” erythrocytes. Hemoglobin electrophoresis is notable for the presence of H hemoglobin. The new generation sequencing confirmed the diagnosis of ATMDS showing a non-sense mutation in the gene ATRX.
The diagnosis of ATMDS should be considered in the presence of the association of MDS, microcytic anemia and marked blood smear abnormalities such as anisocytosis and poikilocytosis. A little less than 10% of all MDS are complicated by ATMDS.
Irreversible electroporation (IRE) is the latest in the series of image-guided locoregional tumor ablation therapies. IRE is performed in a nearly non-thermal fashion that circumvents the "heat sink ...effect" and allows for IRE application in proximity to critical structures such as bile ducts or neurovascular bundles, where other techniques are unsuitable. IRE appears generally feasible and initial reported results for tumor ablation in the liver, pancreas and prostate are promising. Additionally, IRE demonstrates a favorable safety profile. However, site-specific complications include bile leaking or vein thrombosis and may be more severe after pancreatic IRE compared to liver or prostate ablation. There is limited clinical evidence in support of the use of IRE in the kidney. In contrast, pulmonary IRE has so far failed to demonstrate efficacy due to practicability limitations. Hence, this review will provide a state-of-the-art update on available clinical evidence of IRE regarding feasibility, safety and oncologic efficacy. The future role of IRE in the minimally invasive treatment of solid tumors will be discussed.
• Preclinical findings of IRE have been successfully translated into clinical settings.• Non-thermal ablation is able to prevent the "heat sink effect" and collateral damage.• IRE should primarily be applied to tumors adjacent to sensitive structures (e. g. bile ducts).IRE efficacy appears promising in the liver, pancreas and prostate with tolerable morbidity.• In contrast, there are no evidential benefits of IRE in the lung parenchyma. Citation Format: • Savic LJ, Chapiro J, Hamm B et al. Irreversible Electroporation in Interventional Oncology: Where We Stand and Where We Go. Fortschr Röntgenstr 2016; 188: 735 - 745.
Intra-arterial therapies (IATs) play a pivotal role in the management of patients with primary and secondary liver malignancies. The unique advantages of these treatments are their ability to ...selectively deliver a high dose of anticancer treatment while preserving healthy liver tissue. The proven efficacy of these catheter-based locoregional therapies in a highly systemic chemoresistant cancer such as hepatocellular carcinoma (HCC), along with the minimally invasive nature of these treatments, quickly yielded wide acceptance in the medical community and revolutionized the field of Interventional Oncology. In this article, we describe the clinical rationale and background of catheter-based IATs. We provide an overview of clinical achievements of these treatments alone and in combination with sorafenib in patients with HCC.
Alpha thalassemia-myelodysplastic syndrome (ATMDS) is one of the possible complications related to the genetic instability typical of clonal hemopoietic disorders such as myelodysplastic syndromes ...(MDS). Hemoglobin H acquisition, which is hemoglobin without alpha chains and with 4 beta chains is the hallmark of this disease.
An 86-year-old male with chronic, microcytic anemia was referred due to a fall in his hemoglobin level. The blood smear was remarkable for intense anisocytoses and poikilocytosis. Bone marrow analysis was followed by a diagnosis of MDS with a good prognostic score. Peripheral blood coloration with brilliant cresyl blue showed "golf ball-like" erythrocytes. Hemoglobin electrophoresis is notable for the presence of H hemoglobin. The new generation sequencing confirmed the diagnosis of ATMDS showing a non-sense mutation in the gene ATRX.
The diagnosis of ATMDS should be considered in the presence of the association of MDS, microcytic anemia and marked blood smear abnormalities such as anisocytosis and poikilocytosis. A little less than 10% of all MDS are complicated by ATMDS.
The immunoproteasome (IP) is usually viewed as favoring the production of antigenic peptides presented by MHC class I molecules, mainly because of its higher cleavage activity after hydrophobic ...residues, referred to as the chymotrypsin-like activity. However, some peptides have been found to be better produced by the standard proteasome. The mechanism of this differential processing has not been described. By studying the processing of three tumor antigenic peptides of clinical interest, we demonstrate that their differential processing mainly results from differences in the efficiency of internal cleavages by the two proteasome types. Peptide gp100(209-217) (ITDQVPSFV) and peptide tyrosinase369-377 (YMDGTMSQV) are destroyed by the IP, which cleaves after an internal hydrophobic residue. Conversely, peptide MAGE-C2(336-344) (ALKDVEERV) is destroyed by the standard proteasome by internal cleavage after an acidic residue, in line with its higher postacidic activity. These results indicate that the IP may destroy some antigenic peptides due to its higher chymotrypsin-like activity, rather than favor their production. They also suggest that the sets of peptides produced by the two proteasome types differ more than expected. Considering that mature dendritic cells mainly contain IPs, our results have implications for the design of immunotherapy strategies.
Objectives
To determine clinical outcome of patients with vestibular schwannoma (VS) after treatment with fractionated stereotactic radiotherapy (FSRT) and single-session stereotactic radiosurgery ...(SRS) by using 3D quantitative response assessment on MRI.
Materials
This retrospective analysis included 162 patients who underwent radiation therapy for sporadic VS. Measurements on T1-weighted contrast-enhanced MRI (in 2-year post-therapy intervals: 0–2, 2–4, 4–6, 6–8, 8–10, 10–12 years) were taken for total tumour volume (TTV) and enhancing tumour volume (ETV) based on a semi-automated technique. Patients were considered non-responders (NRs) if they required subsequent microsurgical resection or developed radiological progression and tumour-related symptoms.
Results
Median follow-up was 4.1 years (range: 0.4–12.0). TTV and ETV decreased for both the FSRT and SRS groups. However, only the FSRT group achieved significant tumour shrinkage (
p
< 0.015 for TTV, p < 0.005 for ETV over time). The 11 NRs showed proportionally greater TTV (median TTV pre-treatment: 0.61 cm
3
, 8–10 years after: 1.77 cm
3
) and ETV despite radiation therapy compared to responders (median TTV pre-treatment: 1.06 cm
3
; 10–12 years after: 0.81 cm
3
;
p
= 0.001).
Conclusion
3D quantification of VS showed a significant decrease in TTV and ETV on FSRT-treated patients only. NR had significantly greater TTV and ETV over time.
Key Points
•
Only FSRT not GK-treated patients showed significant tumour shrinkage over time.
•
Clinical non-responders showed significantly less tumour shrinkage when compared to responders.
•
3D volumetric assessment of vestibular schwannoma shows advantages over unidimensional techniques.
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