Accurate detection of uniparental disomy and microdeletions by SNP array analysis in myelodysplastic syndromes with normal cytogenetics.

Progress in the management of patients with myelodysplastic syndromes (MDS) has been hampered by the inability to detect cytogenetic abnormalities in 40-60% of cases. We prospectively analyzed matched pairs of bone marrow and buccal cell (normal) DNA samples from 51 MDS patients by single nucleotide polymorphism (SNP) arrays, and identified somatically acquired clonal genomic abnormalities in 21 patients (41%). Among the 33 patients with normal bone marrow cell karyotypes, 5 (15%) had clonal, somatically acquired aberrations by SNP array analysis, including 4 with segmental uniparental disomies (UPD) and 1 with three separate microdeletions. Each abnormality was detected more readily in CD34+ cells than in unselected bone marrow cells. Paired analysis of bone marrow and buccal cell DNA from each patient was necessary to distinguish true clonal genomic abnormalities from inherited copy number variations and regions with apparent loss of heterozygosity. UPDs affecting chromosome 7q were identified in two patients who had a rapidly deteriorating clinical course despite a low-risk International Prognostic Scoring System score. Further studies of larger numbers of patients will be needed to determine whether 7q UPD detected by SNP array analysis will identify higher risk MDS patients at diagnosis, analogous to those with 7q cytogenetic abnormalities

Cáncer de mama durante el embarazo

As women in western countries delay childbearing, it has been hypothesized that the incidence of breast cancer diagnosed during pregnancy will increase. Breast carcinoma during pregnancy(BCP) put the health of the mother in conflict with that of the fetus. The aim is to give optimal treatment to the mother to maximise the chances of survival, whilst minimising the risk of harm of the fetus. Few breast surgeons or oncologist develop expertise in this area owing the rarity of the association. We report the epidemiology, pathology, clinical picture, therapeutic management and fetal outcome of pregnant women with breast cancer treated in our institutio

Acute Myeloid Leukemia: Focus on Novel Therapeutic Strategies

Acute myeloid leukemia (AML) is a heterogeneous disease with variable clinical outcomes. Cytogenetic analysis reveals which patients may have favorable risk disease, but 5-year survival in this category is only approximately 60%, with intermediate and poor risk groups faring far worse. Advances in our understanding of the biology of leukemia pathogenesis and prognosis have not been matched with clinical improvements. Unsatisfactory outcomes persist for the majority of patients with AML, particularly the elderly. Novel agents and treatment approaches are needed in the induction, post-remission and relapsed settings. The additions of clofarabine for relapsed or refractory disease and the hypomethylating agents represent recent advances. Clinical trials of FLT3 inhibitors have yielded disappointing results to date, with ongoing collaborations attempting to identify the optimal role for these agents. Potential leukemia stem cell targeted therapies and treatments in the setting of minimal residual disease are also under investigation. In this review, we will discuss recent advances in AML treatment and novel therapeutic strategies

Triage for surgical management of ovarian tumors in asymptomatic women: assessment of an ultrasound-based scoring system.

OBJECTIVES: To prospectively evaluate an ultrasound-based scoring system as a method for triaging asymptomatic women presenting with an adnexal mass for surgical treatment. METHODS: Two hundred and four adnexal masses in 189 asymptomatic women undergoing elective surgical treatment at our institution were included in this prospective study. Patients were evaluated by transvaginal power Doppler ultrasound imaging before surgery. Patients were classified as low risk or high risk for malignancy according to an ultrasound-based scoring system. Women with a low risk for malignancy were scheduled for laparoscopy and patients with a high risk for malignancy were scheduled for laparotomy. However, patients classified as low risk by the ultrasound scoring system, but with a tumor size >or= 10 cm or clinical suspicion of pelvic adhesions, were instead considered to be at intermediate risk and were scheduled for laparotomy. Some patients classified as high risk were scheduled for an operative laparoscopy by an expert in gynecological oncology. RESULTS: One hundred and thirty-four (65.7%) masses were considered to be low risk and were treated by a laparoscopically guided procedure. All these tumors were benign. Forty-seven (23%) masses were classified as high risk, of which 39 tumors were malignant and eight benign. Twenty-three (11.3%) tumors were considered to be intermediate risk and were scheduled for primary laparotomy. In this group, 21 (91.3%) tumors proved to be benign and two (8.7%) were malignant. CONCLUSIONS: Ultrasound-based triage of asymptomatic women diagnosed with a persistent adnexal mass is effective for selecting the surgical approach

A phase 1b/2b multicenter study of oral panobinostat plus azacitidine in adults with MDS, CMML or AML with less than or equal to 30% blasts

Treatment with azacitidine (AZA), a demethylating agent, prolonged overall survival (OS) vs conventional care in patients with higher-risk myelodysplastic syndromes (MDS). As median survival with monotherapy is <2 years, novel agents are needed to improve outcomes. This phase 1b/2b trial (n=113) was designed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of panobinostat (PAN)+AZA (phase 1b) and evaluate the early efficacy and safety of PAN+AZA vs AZA monotherapy (phase 2b) in patients with higher-risk MDS, chronic myelomonocytic leukemia or oligoblastic acute myeloid leukemia with <30% blasts. The MTD was not reached; the RP2D was PAN 30 mg plus AZA 75 mg/m2. More patients receiving PAN+AZA achieved a composite complete response ([CR)+morphologic CR with incomplete blood count+bone marrow CR (27.5% (95% CI, 14.6–43.9%)) vs AZA (14.3% (5.4–28.5%)). However, no significant difference was observed in the 1-year OS rate (PAN+AZA, 60% (50–80%); AZA, 70% (50–80%)) or time to progression (PAN+AZA, 70% (40–90%); AZA, 70% (40–80%)). More grade 3/4 adverse events (97.4 vs 81.0%) and on-treatment deaths (13.2 vs 4.8%) occurred with PAN+AZA. Further dose or schedule optimization may improve the risk/benefit profile of this regimen

Endometriosis

Endometriosis is a common gynaecological disease of unknown aetiology which affects an estimated 10% to 15% of all premenopausal women. It is defined as the presence of endometrial tissue, consisting of both glandular epithelium and stroma, outside the uterine cavity. Three different clinical entities of endometriosis can be distinguished: peritoneal endometriosis, ovarian endometriosis and deep invasive endometriosis. There are several theories to explain their pathogenesis: metaplasia of the mesothelium, in situ development of Müllerian remnants in the rectovaginal area (deep-invasive lesions) or retrograde transplantation of shed menstrual effluent (peritoneal implants). The most widely accepted hypothesis for the development of endometriosis is retrograde menstruation. However, some other factor renders certain women susceptible to the implantation and growth of this ectopic endometriu

Angiogénesis y endometriosis

Endometriosis is a common gynaecological disease of unknown aetiology. Angiogenesis appears to be one of the processes involved in its pathogenesis. Angiogenic factors are increased in the peritoneal fluid of patients with endometriosis (McLaren 1996 et al; Taylor et al, 2002), in peritoneal implants (Ferriani et al, 1993) and in ovarian endometriomas. On the other hand, some researchers have found that angiogenesis is related to pelvic pain. We speculated that ovarian endometriomas in patients presenting with pelvic pain would be more angiogenic than those in asymptomatic women and that their vascular features would therefore be different

Nuevos horizontes en cirugía mamaria. Cirugía radioguiada y biopsia selectiva de ganglio centinela

Although needle-wire localization is the most commonly used localization technique for nonpalpable breast lesion biopsy, the technique of radioguided occult lesion localization (ROLL), is becoming increasingly used for open-surgery diagnosis in such cases. Sentinel lymph node biopsy(SLNB) is based on the hypothesis that lymphatic drainage from a tumor reaches the sentinel node(SLN) first and that it can be identified accurately and removed. If SLN exactly reflects the lymph-node status, a negative SLN for metastasis might allow complete axillary lymph node dissection (ALDN) to be avoided