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Background Chromoblastomycosis is a deep fungal infection characterized by a complex cellular granuloma. The aim of this study was to analyze the arrangement of cells responsible for the granuloma configuration of this disease by semiquantification of the cellular components of chromoblastomycosis skin biopsies. Methods The cells of cutaneous biopsies slides from 100 patients with untreated chromoblastomycosis were stained with hematoxylin-eosin and the granuloma cells were evaluated by microscopic examination of the elements of each granuloma and semiquantified the number of cells through its expressivity in crosses and the histopathological variables. Their presences were coded in degrees of intensity and classified in two categories: low expression and high expression. The cells that constitute the granulomas were separated into three groups: A, B and C. Results The chromoblastomycotic granuloma analysed by this semiquantification of its cellular components showed that there was high expression of the elements setting up a mixed organized mycotic granuloma. It was observed that mononuclear phagocytic system (A), polymorphonuclear phagocytic system (B) and lymphoplasmocytic infiltrate (C) were located around the fungus. Conclusions The results indicated that the granuloma present in the cutaneous lesion of chromoblastomycosis is the mixed organized mycotic granuloma with high expression of the cellular components.

The use of generic drugs after patent expiration of their originators is a relative novelty in the treatment of chronic cancer patients in Western countries. In this observational study we analyzed a cohort of 294 Italian chronic phase chronic myeloid leukemia patients treated frontline with branded imatinib (Glivec®) for at least 6 months and then uniformly switched to generic imatinib upon requirement of health authorities in early 2017. Median age at diagnosis was 57 years (range 19-87). Sokal risk was low/intermediate/high in 55%, 32% and 8% of cases, respectively. Median duration of branded imatinib treatment was 7.4 years (range 0.5-16.7). At a median follow-up of 7.5 months after switch to generic imatinib, 17% of patients reported new or worsening side effects, but grade 3-4 non-hematological adverse events were rare. Six patients switched back to branded imatinib, with improvement in the side effect profile, and 4 pts moved to bosutinib or nilotinib for resistance/intolerance. The majority of patients were in major (26%) or deep molecular response (66%) at the time of switch. Molecular responses remained stable, improved or worsened in 61%, 25% and 14% of patients, respectively. We conclude that switch to generic imatinib for patients who have been receiving branded imatinib appears to be effective and safe. Molecular responses may continue to improve over time. Some patients experienced new or worsened side effects but less than 5% of the whole cohort needed to switch back to branded imatinib or move to other treatments. Savings were around 3 million Euros.

Melanocytic nevi result from the proliferation of melanocytes at the dermal-epidermal junction and/or in the dermis and very rarely affect the nail matrix and bed. Intradermal nevi are tumors often diagnosed in routine clinical dermatological practice, with typical clinical and histopathologic aspects, and found in a wide variety of skin sites. We report a case of intradermal melanocytic nevus of the proximal nail fold with uncommon intraoperative gross findings and without involvement of the nail bed or matrix, showing intradermal component only, which draws our attention to the possible different presentation of melanocytic lesions. No description of intradermal nevi at this site has been reported in the literature so far.

This paper is a case report of a young patient after a major head trauma causing multiple skull base fractures. The trauma occasioned pseudoaneurysm (PSA) from intracavernous C4 segment of left internal carotid artery (ICA) protruding in the sphenoidal sinus. After two months, two episodes of massive epistaxis occurred. Consequently, the post-traumatic PSA was treated, after carotid occlusion test, with flow-diverter stent positioning. A computed tomography angiography study performed in the following days showed complete resolution of the post-traumatic PSA lesion and ICA patency.

In this past decade, new therapeutic approaches based on the use of rituximab, high-dose cytosine-arabinoside, and autologous stem cell transplantation (ASCT) have changed the paradigm of mantle cell lymphoma (MCL) treatment, significantly improving the quality and duration of response and

The use of flow-diverter (FD) stents in recent years has positively changed the therapeutic approach to some vascular diseases, especially of certain types of aneurysms. This paper describes the case of a young patient after a major head trauma causing multiple skull fractures. The trauma occasioned two pseudoaneurysms from the A1 segment of the right anterior cerebral artery and from the A2 segment of the left anterior cerebral artery. Both lesions were treated with two Pipeline devices (ev3, Irvine, CA, USA) in two different sessions. The CT study and angiographic investigations performed in the following month showed a complete resolution of the post-traumatic pseudoaneurysmal lesions. Although the use of FD stents is described in the literature, particularly in the treatment of selected aneurysms, this paper shows good technical results in the use of these stents in cases of intracranial post-traumatic pseudoaneurysms with clinical improvement.

Pituitary apoplexy is a rare endocrine emergency that occurs in a small number of patients with a pituitary tumor. It is a clinical syndrome characterized by the sudden onset of headache, nausea, vomiting, visual impairment, and decreased consciousness, caused by hemorrhage and/or infarction of the pituitary gland. Pituitary apoplexy has very rarely been described during pregnancy, when it is potentially life-threatening to both the mother and the fetus, if unrecognized. Only a few cases have been published to date. The review of the existing literature underlines that pituitary apoplexy, although rare, should be borne in mind when a pregnant woman presents with severe headache and visual defects of sudden onset. After initial management, which includes intravenous glucocorticoid therapy, fluid and electrolyte replacement, the final selection of medical or surgical treatment should result from a multidisciplinary approach involving expert specialists, keeping into account both severity of clinical presentation and gestational week.

O objetivo deste estudo foi delinear o perfil das crianças atendidas no Ambulatório de Saúde Mental de Içara - SC. Portanto, realizou-se uma pesquisa documental, de abordagem quantitativa e de natureza exploratória. A coleta de dados deu-se através dos prontuários das crianças de 6 a 11 anos atendidas no período de 2013 a junho de 2016. Observou-se que 58,3% eram do sexo masculino, 38,3% tem idade entre 8 e 9 anos e 27% são encaminhados por suspeita de transtorno do neurodesenvolvimento. Sobre o trabalho realizado no local, pode-se inferir que 53% são atendidas pela psicóloga, 31% fazem psicoterapia, 21% usam medicação e 12% associam psicoterapia com psicofármaco. É necessário pensar em ações para esta demanda sob uma lógica biopsicossocial. Conhecer o usuário torna possível encontrar subsídios para repensar as práticas atuais e formular melhores métodos de atuação.

Lhermitte-Duclos disease is a rare pathologic condition consisting of a dysplastic gangliocytoma of the cerebellum. Its association with phacomatosis and an autosomal dominant neoplastic syndrome, Cowden's syndrome is also known. Modern neuroimaging contributes to a correct diagnosis and pre- and postoperative evaluation. Here we describe the morphologic and metabolic aspects of the disease as shown by conventional MRI, diffusion imaging and spectroscopy in a 31-year-old woman. In addition, the specific neuroradiologic characteristics are presented and discussed in the light of the main pathologic and clinical features, such as hypertrophy of the cerebellar folia associated with white matter atrophy.

The impact of residual pulmonary obstruction on the outcome of patients with pulmonary embolism is uncertain.We recruited 647 consecutive symptomatic patients with a first episode of pulmonary embolism, with or without concomitant deep venous thrombosis. They received conventional anticoagulation, were assessed for residual pulmonary obstruction through perfusion lung scanning after 6 months and then were followed up for up to 3 years. Recurrent venous thromboembolism and chronic thromboembolic pulmonary hypertension were assessed according to widely accepted criteria.Residual pulmonary obstruction was detected in 324 patients (50.1%, 95% CI 46.2–54.0%). Patients with residual pulmonary obstruction were more likely to be older and to have an unprovoked episode. After a 3-year follow-up, recurrent venous thromboembolism and/or chronic thromboembolic pulmonary hypertension developed in 34 out of the 324 patients (10.5%) with residual pulmonary obstruction and in 15 out of the 323 patients (4.6%) without residual pulmonary obstruction, leading to an adjusted hazard ratio of 2.26 (95% CI 1.23–4.16).Residual pulmonary obstruction, as detected with perfusion lung scanning at 6 months after a first episode of pulmonary embolism, is an independent predictor of recurrent venous thromboembolism and/or chronic thromboembolic pulmonary hypertension.

Background To evaluate the HPV vaccination coverage in Boa Vista, Roraima (Brazil) and to identify personal and socioeconomic factors related to non-compliance to HPV vaccination. Methods A school-based, cross-sectional study was conducted by distributing a self-administered questionnaire to the parents or guardians of pre-adolescent girls. The questionnaire addressed compliance to, knowledge about and perception of HPV and the HPV vaccine. Between July and November 2015, 13 private and public schools were visited based on a random cluster sampling method. Results A total of 1337 questionnaires were distributed to all female students in the target age group, and 797 were completed and returned (the participation rate was 59.6 %). The vaccination coverage rate was 82.7 % and was higher among public school students than among private school students (84.1 % vs 56.3 %; p = 0.003). Most parents (60 %) incorrectly answered more than half of the questions related to HPV knowledge, and limited knowledge about HPV and the HPV vaccine correlated with lower compliance to vaccination (adjusted OR = 1.42; 95 % CI: 1.01 to 2.76). In the perception analysis, the belief that the HPV vaccine is important for the daughter was an important protective factor (adjusted OR = 0.62; 95 % CI: 0.23 to 0.93), and concern about adverse effects of the HPV vaccine was a risk factor for non-compliance (adjusted OR = 1.66; 95 % CI: 1.01 to 2.71). Family income, religion and education level of the parents or guardians did not correlate with compliance to vaccination. Conclusion HPV vaccination coverage was high in Boa Vista, Brazil, but knowledge about the vaccine was deficient. This deficiency was associated with a distorted perception and was negatively associated with compliance to vaccination. Actions aimed at informing the public about the HPV vaccine, including its risks and benefits, are needed to attain higher vaccination coverage in Brazil. Electronic supplementary material The online version of this article (doi:10.1186/s12913-016-1677-y) contains supplementary material, which is available to authorized users.

The aim of this study is to explore the possibility of endovascular treatment of internal carotid artery pseudoaneurysm (PSA). These lesions are difficult to treat with a surgical approach, especially if they are located extracranially and close to the skull base. Endovascular stent placement in symptomatic and unstable extracranial internal carotid PSA was found to be safe and effective. Depending on hemodynamic aspects, complete local exclusion of aneurysmal formation is achieved in few months. We present three patients with carotid dissection and PSA formation that have been successfully treated by stent placement.

Phaeohyphomycosis is a disease caused by dematiaceous fungi with a worldwide geographic distribution and broad spectrum. It is most commonly found in adult individuals of both genders and all races. We report the case of a 57-year-old woman with phaeohyphomycosis in the ungual apparatus.

Background In up to 80% of patients with pulmonary embolism (PE) no peripheral symptomatic thrombosis can be identified. Whether the heart may represent a source of PE is unknown. Methods We conducted a cross-sectional survey of patients who were 60 years or older and were discharged from the hospitals of Veneto region, Italy between 2000 and 2006 with the diagnosis of PE. We compared the prevalence of several acute and chronic heart diseases in patients discharged with the diagnosis of PE alone with that of patients with co-occurring symptomatic peripheral deep venous thrombosis (PE/DVT). Results Out of 11,236 eligible patients, 9079 (81%) were discharged with the diagnosis of PE alone, and 2157 with that of PE/DVT. 3239 of the 9079 (35.7%) patients with isolated PE, and 666 of the 2157 (30.9%) with PE/DVT had at least one heart disease. The adjusted odds ratio (OR) for having at least one heart disease in patients with isolated PE as compared to those with PE/DVT was 1.26 (95% CI, 1.13–1.40). The heart diseases that significantly contributed to the study results were all-cause cardiomyopathies (adjusted OR, 2.31; 95% CI, 1.37–3.89), all-cause heart failure (1.82; 1.45–2.27), coronary heart disease (1.28; 1.08–1.52), and atrial fibrillation or flutter (1.28; 1.08–1.51). Conclusions There is an association between isolated PE and a number of heart diseases. The results of our survey generate the hypothesis that in older patients several heart diseases may directly account for the development of PE. Prospective studies are needed to confirm this hypothesis.

Reduced-intensity conditioning (RIC) regimens for allogeneic hematopoietic stem cell transplantation (HCT) allowed the existence of an allogeneic cell-mediated antitumor effect in metastatic colorectal cancer (mCRC) to be explored. We report on 39 patients with progressing mCRC treated with different RIC regimens in a multicenter clinical trial of the European Bone Marrow Transplantation Group. Disease status at transplant was progressive disease (PD) in 31 patients (80%), stable disease (SD) in 6 (15%), and partial response (PR) in 2 (5%). All patients engrafted (median donor T cell chimerism of 90% at day +60). Transplant-related morbidities were limited. Grades II-IV acute graft-versus-host disease (aGVHD) occurred in 14 patients (35%) and chronic GVHD (cGVHD) in 9 patients (23%). Transplant-related mortality occurred in 4 patients (10%). The best tumor responses were: 1 complete response (CR) (2%), 7 PR (18 %), and 10 SD (26%), giving an overall disease control in 18 of 39 patients (46%). Allogeneic HCT after RIC is feasible; the collected results compared favorably in terms of tumor response with those observed using conventional approaches beyond second-line therapies. The study of an allogeneic cell based therapy in less advanced patients is warranted.

We analyzed individual VH gene rearrangements in 55 consecutive B-chronic lymphocytic leukemia (B-CLL) patients collected from a northeastern region of Italy, stressing the possible differences related to geographic characteristics of the cohorts studied. Considering the percentage of somatic mutations present in the VH gene sequences and using the 98% cut-off value, 38 of the 55 B-CLL (69%) patients displayed somatic hypermutations and 17 (31%) had a germline configuration. Our results confirm and extend the observations of a bias in the use of certain VH, DH, and JH genes among B-CLL cells. The most frequently used VH genes were VH1-69 (12.7%) with VH3-23 (12.7%) and VH4-34 (10.9%). Collectively these genes accounted for 36.3% of the cases. In the mutated cases, the range of mutations varied from 2% to 15%, with a median of 6.5%. VH1-69 (7 cases, all unmutated) carried few mutations as opposed to VH3-23 (7 cases, 5 of which mutated), VH4-34 (6 cases, all mutated), and VH3-30 (5 cases, all mutated), which show a high load of mutations. D3 family genes were found frequently (38.1%) followed by D2 (27.2%) and D6 (18.1%). The individual D segment most frequently used was D3-3, which was present in 16.3% of cases. There was predominance of the JH4 gene (49%) followed by JH6 (40%). Analysis of the distribution of replacement and silent mutations in the mutated sequences using the method of Lossos showed in 39.4% of cases evidence of antigen selection in the framework region and/or complementary determining regions. In comparison with a recent study on B-CLL patients from the Mediterranean area, the VH4-34 gene was significantly overused in the mutated group at a percentage double that of the Italian cohort reported in this study (10.9% vs. 5%), but at a frequency similar to the entire Mediterranean region (10.7%). We also found an over-representation of VH1-69 usage in the germline group, at a frequency (12.7%) higher than previously described by the same authors (Italian 8%, Mediterranean 10.7%). On the contrary, VH3-07 and VH3-49 were not much used in our study (5.4% and 1.8%, respectively) compared with the Italian group (8% and 5.1%). In our study, VH3-23 gene segment was frequently expressed, at frequency as high as that of VH1-69, a finding in keeping with reported B-CLL Italian data, but higher than the entire series of the Mediterranean area (12.7% vs. 9.2%); VH3-21 gene, frequently expressed in northern European CLL but rarely in the Mediterranean area, was completely absent. This biased usage of VH family genes may reflect a geographic leukemic repertoire, perhaps owing to a peculiar genetic background, depending on variations in germline composition of the IgVH locus or to the effect of a potential environmental element less frequently encountered in different regions.

Purpose: This phase II trial of induction irinotecan/gemcitabine followed by twice-weekly gemcitabine and upper abdominal radiation was initiated to determine the activity of this regimen in patients with unresectable pancreatic cancer. Methods: Patients with locally advanced, nonmetastatic adenocarcinoma of the pancreas received 2 cycles of induction irinotecan (100 mg/m 2 IV) and gemcitabine (1000 mg/m 2 IV) on days 1 and 8 of each 3-week cycle. Following the induction, patients without disease progression received gemcitabine administered twice weekly (40 mg/m 2 /day) for 5 weeks concurrent with upper abdominal radiation (50.4 Gy over 5.5 weeks). Results: From April 2000 to August 2003, 20 patients were entered into this study, 17 of whom were evaluable for treatment response. Characteristics included a median age of 67 years (range, 44-87 years) and 14 men (70%). Grades III and IV hematologic toxicity occurred in 25% and 5% of patients respectively and was primarily thrombocytopenia. No grade IV gastrointestinal toxicities or deaths due to therapy were observed. All therapy was completed in 8 patients, 7 patients were removed due to progression, 2 due to toxicity, 2 refused further treatment, and 1 was removed per the treating physician. The median time to progression and median survival was 5.1 months (95% CI, 3.2-6.7) and 8.8 months (95% CI, 6.4-10.1) respectively. Four patients (20%) were alive at 12 and 18 months. Conclusion: Induction irinotecan/gemcitabine followed by twice-weekly gemcitabine and upper abdominal radiation is feasible in patients with locally advanced pancreatic cancer. This regimen, however, has only modest activity and should not be explored further.

Introduction In this retrospective real-life study in relapsed/refractory multiple myeloma patients, we analyzed clinical and biologic features distinguishing patients with rapidly progressing disease while receiving lenalidomide therapy from those without progression. Patients and Methods According to time of stopping lenalidomide, patients were subdivided into 3 groups: early stop (ES) (n = 23), when therapy was discontinued within 6 months; intermediate (INT) (n = 23), when therapy was stopped between 7 to 24 months; and long survival (LS) (n = 45), when therapy was maintained for more than 2 years. The median age of the whole cohort was 70 years (range, 42-85 years); 40% had an International Staging System score of 2 or 3. Results High-risk cytogenetic findings, including 1q gain, was reported in 65% ES, 43% INT, and 21% LS. Overall response rate was 63%, with median progression-free survival and overall survival of 33 and 56 months, respectively. Conclusion Although high-risk cytogenetic findings negatively affect progression-free survival and overall survival, 28% of cytogenetic high-risk patients experienced long survival, provided that lenalidomide therapy was not discontinued, thus pointing to the role of maintenance therapy in this subset of patients.

Background: If not diagnosed earlier, chromoblastomycosis has a chronic evolutional course that may cause several problems, such as difficulty in managing therapy because of the recrudescent character of the disease, potential association with the growth of epidermoid carcinoma in affected regions, and poor quality of life and work incapacity to the patient. Although infrequent, new cases are reported in the state of Rio Grande do Sul every year, ratifying the necessity for further studies on this disease. Objective: The purpose of this study was to review clinical features and response to therapy in patients with chromoblastomycosis and present data on the demography and history of this disease in the state of Rio Grande do Sul, Brazil. Methods: We reviewed case records of 100 patients with skin lesions caused by chromoblastomycosis, who were treated between 1963 and 1998. The cases were confirmed by the histopathologic and mycologic analyses made by the Dermatology Service of the Universidade Federal do Rio Grande do Sul at the Santa Casa de Misericordia Hospital. Results: There was a predominance of male patients (4:1) and of white farmers whose ages ranged from 50 to 59 years, with lesions on their lower limbs. Most of them were from the northern regions of the state. The average time between the appearance of the disease and medical diagnosis was 14 years. The verrucous type proved to be the most frequently reported lesion (53%). Thorn wounds were associated with the disease in 16% of the cases. Lesions uncommon to some parts of the body were also reported. In two of the cases, cutaneous lesions caused by paracoccidioidomycosis and chromoblastomycosis were found in the same patient. Epidermoid carcinoma was found in the same parts of the body affected by chromoblastomycosis. Eumycotic mycetoma and chromoblastomycosis were associated. Fonsecaea pedrosoi was found in 96% of the cases, and Phialophora verrucosa in 4% of the cases. Conclusion: In our study, we observed a predominance of cases in the regions of Missoes and Alto Uruguay, followed by the upper and lower northeastern slopes and the lowlands. Severe cases of chromoblastomycosis with intense skin involvement (eg, lesions with carcinoma) were observed. Statistical analysis showed recrudescence of the disease in 43% of cases despite the treatment used. (J Am Acad Dermatol 2001;44:585-92.)

Nine patients with previously unreported chromosome changes were identified among 209 B-cell chronic lymphocytic leukaemia (CLL) cases: three patients had a translocation involving 6p24-25; three had a 12p12-13 translocation; two had 4q21 involvement (one with coexisting 6p anomaly); and two had monosomy 21. Interphase fluorescence in situ hybridization (FISH) detected some cryptic aberrations (+12, 6q-, 17p-, 11q-) in those patients with 6p translocations, whereas only a cytogenetically undetected 13q14 deletion was found in the remaining cases. Atypical morphology was noted in six cases, including both cases with monosomy 21, two cases with 6p and 4q21 anomaly and one case with 12p involvement. Four of these cases also had more than one phenotype deviation with respect to the classical CLL phenotype. Disease progression after 21-51 months (median 41) was noted in two cases with 6p and 4q21 involvement and in one case with 12p anomaly and monosomy 21. We arrived at the following conclusions: (i) 6p24-25 and, possibly, 4q21 lesions represent non-random events in CLL, occurring in association with other well-known unbalanced rearrangements; (ii) 12p rearrangements and monosomy 21 may possibly represent early chromosome defects that are not associated with the classical DNA gains and losses known to be present in the majority of CLL; and (iii) atypical morphology and immunophenotype as well as disease progression were frequently observed in these cases

To better define the role of exposure to myelotoxic agents in the genesis of myelodysplastic syndrome (MDS), we carried out (a) a case-control study for the determination of the relative risk (RR) of developing MDS, including 178 consecutive patients and 178 sex- and age-matched controls: (b) a study of clinicobiological features in MDS arising after occupational exposure to myelotoxic agents and in MDS in 'non-exposed' patients. The definition of the 'exposure' status was based on a predetermined questionnaire, with calculation of an 'exposure' index (hours/day x days/year x years). Cumulative exposure to pesticides or to organic solvents, for >2400 h, was recorded in 48 and 25 MDS patients, respectively, compared to 27 and four controls (P

The expression levels of human antioxidant genes (HAGs) and oxidative markers were investigated in light of lung adenocarcinoma aggressiveness and patient outcome. We assayed in vitro the tumoral invasiveness and multidrug resistance in human lung adenocarcinoma (AdC) cell lines (EKVX and A549). Data were associated with several redox parameters and differential expression levels of HAG network. The clinicopathological significance of these findings was investigated using microarray analysis of tumor tissue and by immunohistochemistry in archival collection of biopsies. An overall increased activity (expression) of selected HAG components in the most aggressive cell line (EKVX cells) was observed by bootstrap and gene set enrichment analysis (GSEA). In vitro validation of oxidative markers revealed that EKVX cells had high levels of oxidative stress markers. In AdC cohorts, GSEA of microarray datasets showed significantly high levels of HAG components in lung AdC samples in comparison with normal tissue, in advanced stage compared with early stage and in patients with poor outcome. Cox multivariate regression analysis in a cohort of early pathologic (p)-stage of AdC cases showed that patients with moderate levels of 4-hydroxynonenal, a specific and stable end product of lipid peroxidation, had a significantly less survival rate (hazard ratio of 8.87) (P

In this work a fully automatic algorithm to detect brain tumors by using symmetry analysis is proposed. In recent years a great effort of the research in field of medical imaging was focused on brain tumors segmentation. The quantitative analysis of MRI brain tumor allows to obtain useful key indicators of disease progression. The complex problem of segmenting tumor in MRI can be successfully addressed by considering modular and multi-step approaches mimicking the human visual inspection process. The tumor detection is often an essential preliminary phase to solvethe segmentation problem successfully. In visual analysis of the MRI, the first step of the experts cognitive process, is the detection of an anomaly respect the normal tissue, whatever its nature. An healthy brain has a strong sagittal symmetry, that is weakened by the presence of tumor. The comparison between the healthy and ill hemisphere, considering that tumors are generally not symmetrically placed in both hemispheres, was used to detect the anomaly. A clustering method based on energy minimization through Graph-Cut is applied on the volume computed as a difference between the left hemisphere and the right hemisphere mirrored across the symmetry plane. Differential analysis involves the loss the knowledge of the tumor side. Through an histogram analysis the ill hemisphere is recognized. Many experiments are performed to assess the performance of the detection strategy on MRI volumes in presence of tumors varied in terms of shapes positions and intensity levels. The experiments showed good results also in complex situations.

SummaryRecently, a diagnostic strategy using a clinical decision rule, D-dimer testing and spiral computed tomography (CT) was found to be effective in the evaluation of patients with clinically suspected pulmonary embolism (PE). However, the rate of venous thromboembolic complications in the three-month follow-up of patients with negative CT was still substantial and included fatal events. It was the objective to evaluate the safety of withholding anticoagulants after a normal 64-detector row CT (64-DCT) scan from a cohort of patients with suspected PE. A total of 545 consecutive patients with clinically suspected first episode of PE and either likely pre-test probability of PE (using the simplified Wells score) or unlikely pre-test probability in combination with a positive D-dimer underwent a 64-DCT. 64-DCT scanning was inconclusive in nine patients (1.6%), confirmed the presence of PE in 169 (31%), and ruled out the diagnosis in the remaining 367. During the three-month follow-up of the 367 patients one developed symptomatic distal deep-vein thrombosis (0.27%; 95%CI, 0.0 to 1.51%) and none developed PE (0 %; 95%CI, 0 to 1.0%). We conclude that 64-DCT scanning has the potential to safely exclude the presence of PE virtually in all patients presenting with clinical suspicion of this clinical disorder.

Os autores relatam o caso de recém-nascido do sexo feminino com crises convulsivas e lesões vesiculosas no nariz e lábio inferior, desde o quinto dia de vida. O exame do LCR mostrou alterações compatíveis a encefalite. Houve deterioração do quadro neurológico e respiratório, com morte da paciente. A autópsia parcial do crânio revelou cérebro edemaciado com área necro-hemorrágica envolvendo ambos os lobos temporais. O exame histopatológico revelou encefalite necro-hemorrágica, sem a presença de inclusões intranucleares. O exame imuno-histoquímico, realizado pela técnica da avidina-biotina-peroxidase utilizando anticorpos policlonais contra vírus Herpes simplex tipo 1 e tipo 2, mostrou-se positivo em numerosas células neuronais, astrocíticas e, principalmente, oligodendrogliais para o anticorpo contra o vírus Herpes simplex tipo 2.

As encefaloceles basais são entidades raras e correspondem a herniações do tecido cerebral através de um defeito do crânio, ao longo da lâmina crivosa etmoidal ou do osso esfenoidal. A rara síndrome morning glory, com alterações de fundo de olho características pode apresentar-se associada à encefalocele basal. Deficiências hormonais hipofisárias podem ocorrer. Relatamos caso de nanismo hipofisário com encefalocele transesfenoidal de diagnóstico tardio associada à síndrome de morning glory, mostrando as alterações na retinografia, tomografia computadorizada e ressonância magnética. The basal encephaloceles refer to rare entities and they correspond to herniation of brain tissue through defects of skull along the cribiform plate or the sphenoid bone. A rare morning glory syndrome, with characteristic retinal defect has been reported in association with basal encephaloceles. Hypophysis hormonal deficiencies may occur. We accounted for a pituitary dwarfism with delayed diagnosed transsphenoidal encephalocele associated with morning glory syndrome, showing the alterations found in retinography, computed tomography and magnetic resonance imaging. UNIFESP DDI Neuroradiology Department UNIFESP DDI UNIFESP Pediatrics Endocrinology Department UNIFESP Ophthalmology Department UNIFESP, DDI Neuroradiology Department UNIFESP, DDI UNIFESP, Pediatrics Endocrinology Department UNIFESP, Ophthalmology Department SciELO

PURPOSE: To study the clinicobiologic significance of acquired 11q deletions involving the ataxia teleangiectasia locus (ATM+/−) in B-cell non-Hodgkin’s lymphomas (NHL). PATIENTS AND METHODS: Fifty-three indolent lymphomas and 82 aggressive lymphomas were studied by conventional cytogenetic analysis and by fluorescence in situ hybridization using an 11q22–23 probe recognizing ATM sequences. Pertinent clinical data were collected. RESULTS: A hemizygous ATM deletion was seen in 44% to 88% of the interphase cells in 15 cases (11.1%); four patients had an indolent lymphoma (follicular center cell lymphoma), and 11 patients had an aggressive lymphoma (five mantle-cell lymphomas [MCLs] and six diffuse large-cell lymphomas). Dual-color hybridization studies showed ATM deletion to be possibly a secondary aberration in three patients with MCL. Ten out of 15 ATM+/− patients had a complex karyotype, 11 out of 15 had more than 90% abnormal metaphases (AA karyotype status), and +12, 13q14 deletion, and 17p13 deletion were seen in seven, four, and five cases, respectively. Patients with ATM+/− more frequently had a complex karyotype (P = .01) and the AA karyotype (P = .04) compared with patients without ATM+/−. With the exception of a poor performance status (P = .001), no correlation was found between ATM+/−, initial clinical variables, and complete remission rate; whereas a highly significant association was found with shorter survival (P < .0001). This cytogenetic lesion maintained its prognostic importance in multivariate analysis (P = .0004), along with performance status (P = .0006), serum lactate dehydrogenase level (P = .03), splenomegaly (P = .01), and histologic grade (P = .03). When analyzing indolent lymphomas and aggressive lymphomas separately, ATM+/− maintained its prognostic importance as an independent variable in both histologic groups (P = .0001 and P = .016, respectively). CONCLUSION: Though possibly not representing a primary genetic lesion in the majority of cases, the acquired ATM+/− status has clinicobiologic importance in NHL, possibly representing a major cytogenetic determinant of outcome.

INTRODUCTION We retrospectively analyzed the impact on post-relapse survival of selected prognostic factors and salvage therapy (finalized to perform an allo-SCT) in 145 patients (pts) with non-APL AML who had been initially treated with standard induction and risk-adapted consolidation. The aim was to identify factors associated with a better outcome at first relapse. METHODS All pts were at first recurrence following consolidation of CR1 with (i) high-dose Ara-C (HiDAC) multicycle therapy supported by blood stem cells (standard risk, as defined by mixed clinico-cytogenetic criteria) or (ii) allo-SCT in case of high-risk prognostic profile. Median pt age was 55 y (range 21–68). CR1 duration was ≤ 6 months in 49 pts (34%), ranging from 0.6 to 6 mo (median 3.7). 25/68 pts (37%) had an unfavourable cytogenetics (CG), and 8.2 % had MDS-related AML. 96 pts (66%) had received HiDAC and 21 (15%) an allo-SCT according to study design. RESULTS 105 pts (72%) received salvage chemotherapy, 10 pts (7%) underwent directly allo-SCT, while the remaining 30 (21%) received palliation and all of them died. Salvage therapy consisted again of HiDAC alone or in combination with fludarabine or anthracyclines. After reinduction, 52/105 pts (49.5%) achieved CR2 and 15 (14%) died of complications. Altogether, 42 pts (29%, group 1) received an allo-SCT following relapse, 27 (64%) in CR2, 5 beyond CR2 and 10 soon after relapse. Of 20 more pts (14%, group 2) in CR2 but without HLA identical donor, 13 could be given further intensive consolidation therapy. Both groups were comparable regarding adverse prognostic features such as age >55 y, WBC count>50,000/μL, unfavourable CG, presence of FLT-3 ITD, prior allo-SCT and 1st CR lasting ≤ 6 mo. At the end of treatment, 37/42 pts (88%) receiving SCT and all 20 pts (100%) given only chemotherapy were in CR2. Logistic regression analysis showed that intensive treatment without HiDAC at induction (p=0.04) as well as CR1 lasting CONCLUSIONS AML patients receiving intensive chemotherapy including HiDAC at 1st relapse reached a high CR2 rate, regardless of type of prior risk-adapted consolidation. Further intensification with allo-SCT may offer substantial salvage rates to younger standard risk patients, thus adding value to the underlying concept of a risk-oriented first-line therapy.

3596 Background: Allogeneic reduced intense conditioning regimens decreased morbidity and mortality related to hematopoietic stem cell transplantation (HCT), retaining a powerful graft versus tumor effect (GVT). On this basis, it became possible to explore the existence of alloreactivity in solid tumors. A GVT effect was described in metastatic colorectal cancer (CRC). Methods: We report the data on 35 patients with CRC treated with non-myeloablative allogeneic HCT in Europe. Median time from the diagnosis of metastatic disease to transplant was 16 (4–47) months; 25 patients (67%) received at least 2 lines of therapy before transplant. Disease status at transplant was progressive disease (PD) in 31 patients (80%), stable disease (SD) in 6 (14%) and partial response (PR) in 2 (6%). Patients were treated according to different nonmyeloablative regimens. All but one patient received allogeneic peripheral hematopoietic cells [median CD 34+ cells/kg was 6.7 × 106 (2,5–55), median CD3 + cells/kg was 4.9 × 108 (0,11–33)] from HLA identical familiar donors. GVHD prophylaxis consisted of cyclosporine A (CyA) + Mycophenolate Mofetil in 24 (68%), of CyA + methotrexate in 6 (25%) and other CyA regimens in the others (18%). Results: Myelosuppression was mild and all patients engrafted with a median donor chimerism of 90% (45–99) on CD 3 cells on day +60. Transplant-related toxicities were limited. Grades II-IV acute GVHD occurred in 18 patients (51%) and chronic GVHD in 6 patients (25%). Transplant-related mortality was the cause of death in 4 patients (11%). As best tumor response we observed: 1 complete response (3%), 8 PRs (20%) and 9 SDs (29). Overall median survival from the date of transplant was 198 days (6–1020); median overall survival for the responding patients was 353 days (113–1020). Conclusions: Allogeneic HCT after RIC is safe and feasible in metastatic CRC. The results obtained compared favorably with those observed in patients with hematologic malignancies or metastatic CRC beyond second line in terms of transplant-related complications and tumor response respectively. Thus a study of allogeneic cell therapy in a less advanced patient cohort is warranted. No significant financial relationships to disclose.

In adult ALL standard prognostic models do not predict relapse with great accuracy, which implies under-/over-exposure to a given therapy, especially transplants. A study is exploiting MRD as “best” predictive factor and decisional aid for therapy in unselected patients. Adults with ALL underwent induction-consolidation with IDR/V/ASP/P/CY (cycles 1–3,5,6,8), HD-MTX/Ara-C (cycles 4,7), and CNS prophylaxis. Imatinib was added in Ph+ ALL. For MRD, 3 marrow samples were taken before cycles 4, 6, 8, to be analyzed by PCR/RQ-PCR with case-specific probe(s) targeting fusion genes or Ig-H/TCR rearrangements. MRD negativity was defined as negative/low-positive (100 and adverse cytogenetics predicted to some extent an MRD+ result (P=0.05), while MRD negativity was always confirmed as early as TP1 (week 10). Only 6 MRD− cases relapsed (17%), 1 with a new clone and 4 with suboptimal MRD study, compared to 20/44 (45.5%) MRD+ (P=0.000). DFS at 4 years was 76% in MRD− vs. 24% in MRD+ vs. 54% in the unknown MRD group. In multivariate analysis MRD was stronly predictive for relapse (RR 5.51, P=0.000) followed by a WBC count >30 (RR 3.64, P=0.001), the latter effect being almost exclusively seen in MRD+ patients. As regards MRD monitoring, conversion rate from MRD+ to MRD− was similar after SCT and “hypercycles” in the few cases evaluable (4/6 in each group), with a strong correlation in every prognostic/treatment group between overt relapse and prior positive MRD test (2/35 MRD− vs. 9/20 MRD+; P=0.000). MRD is an invaluable prognostic tool for risk-oriented trials. Both an early analysis and monitoring support optimal therapeutic choices (with some reported exceptions), identify patients at greatest risk of relapse, and could allow comparative trials testing specific treatment elements in different ALL subsets.

8202 Background: Cancer and treatment related factors are traumatic events for the patients. In fact, a large majority of patients experience disruption in their quality of life through loss of rol...