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We report the case of a 14-year-old girl who experienced a Lisfranc fracture-dislocation while playing sport. The lesion was treated with surgery, consisting of open reduction and internal fixation using cannulated screws and Kirschner wires. After one year of follow-up, the patient has no symptoms and no X-ray evidence of degenerative changes in the midfoot. In our view, the surgical procedure, using rigid fixation for the medial column and the second ray, and a provisional fixation to all other rays, allowed for a satisfactory short-term result in this patient. We have used this case to review the management of this lesion in the pediatric population. [Arch Clin Exp Surg 2019; 8(2.000): 53-57]

The aim of this study was to identify an easily reliable prognostic score that selects the subset of advanced soft tissue sarcoma (ASTS) patients with a higher benefit with trabectedin in terms of time to progression and overall survival. A retrospective series of 357 patients with ASTS treated with trabectedin as second- or further-line in 19 centers across Spain was analyzed. First, it was confirmed that patients with high growth modulation index (GMI &gt, 1.33) were associated with the better clinical outcome. Univariate and multivariate analyses were performed to identify factors associated with a GMI &gt, 1.33. Thus, GEISTRA score was based on metastasis free-interval (MFI ≤ 9.7 months), Karnofsky &lt, 80%, Non L-sarcomas and better response in the previous systemic line. The median GMI was 0.82 (0–69), with 198 patients (55%) with a GMI &lt, 1, 41 (11.5%) with a GMI 1–1.33 and 118 (33.1%) with a GMI &gt, 1.33. The lowest GEISTRA score showed a median of time-to-progression (TTP) and overall survival (OS) of 5.7 and 19.5 months, respectively, whereas it was 1.8 and 3.1 months for TTP and OS, respectively, for the GEISTRA 4 score. This prognostic tool can contribute to better selecting candidates for trabectedin treatment in ASTS.

Neuroendoscopy enables diagnostic biopsy of intraventricular and/or paraventricular tumors and the simultaneous treatment of associated hydrocephalus in selected cases. The objective of this paper was to analyze the effectiveness and safety of this procedure. This retrospective study included 80 patients between 2 months and 78 years old diagnosed with intraventricular and/or paraventricular expansive lesion who underwent neuroendoscopic biopsy from 2004 to 2016. Collected variables were gender, age at diagnosis, clinical presentation, tumor location, surgical technique, management of hydrocephalus, pathological findings, procedure-related complications, and follow-up time. Neuroendoscopic biopsy was performed in 80 patients. Mean age at diagnosis was 27 years, and 52.5% were men. According to the Depreitere Classification, 71 were level I (conclusive diagnosis), 1 level III (problematic categorization), and 8 level IV (non-interpretable diagnosis). The most frequent diagnosis was grade I astrocytoma (14%). Diagnostic success per patient was 88.7%. Sixty-nine patients had hydrocephalus at diagnosis, 37 of whom were treated with endoscopic third ventriculostomy (ETV), with septostomy (SPT) in 14, and only SPT in 4. Twenty-eight patients underwent ventricular peritoneal shunt (VPS), with SPT in 20. The ETV success rate was 70.9%. The complication rate per patient was 11%: five patients presented intraventricular hemorrhage, three of whom died; one patient presented cerebrospinal fluid fistula; three presented transient oculomotor impairment. Postoperative follow-up was from 1 month to 12.4 years (mean 45 months). Neuroendoscopy is an effective procedure for the pathological diagnosis of intraventricular and paraventricular tumors, allowing the treatment of associated hydrocephalus. Nevertheless, it is not exempt from serious complications and requires proper training.

Background Improved shunt survival and a better understanding of factors related to failure in paediatric hydrocephalus still pose a challenge for neurosurgeons, in order to avoid morbidity and mortality, as well as the economic impact of repeated revision surgeries. For these reasons, an analysis is performed on the factors related to the first shunt failure in the long-term follow-up of a series in a single centre. Methods A retrospective review was conducted on 166 hydrocephalic paediatric patients shunted for the first time between 2000 and 2014. An analysis was made of the statistical relationships between first shunt failure and the demographic, aetiological, surgical and clinical variables. Results Of the 166 shunts implanted in our centre during the study period, 111 required revision over a mean follow-up period of 93 months. Factors significantly related to failure were post-haemorrhagic and post-infectious hydrocephalus, meningitis episode, posterior burr hole, differential pressure valve, standard catheter in first surgery, and symptomatic over-drainage. Multivariable analysis showed that previous meningitis and symptomatic over-drainage were risk factors for shunt failure, whereas frontal burr hole location and antibiotic-impregnated catheters were protective factors. Cox regression determined that independent factors significantly related to a worse shunt survival, were shunt infection and symptomatic over-drainage. Conclusions Meningitis, symptomatic over-drainage, frontal burr hole, and antibiotic impregnated catheters are significant prognostic factors for shunt survival. Shunt infection and symptomatic over-drainage are independent factors significantly related to a shorter shunt survival. Prospective, randomised, controlled trials are required to validate these results.

Shunt overdrainage in patients with hydrocephalus still represents a challenge for neurosurgeons, in part due to the lack of agreement or uniformity concerning the entity. Important problems exist relating to the real incidence of the entity, its definition, classification, and the pathophysiological theories behind the various treatment strategies proposed. Recent reports have suggested that the evidence about overdrainage and its consequences is not so robust as presumed. Consequently, the topic requires more detailed examination. In this review, we comment on all the main facets related with shunt overdrainage.

Introducción. Según la Organización Mundial de la Salud (OMS) la epilepsia constituye uno de los trastornos neurológicos más frecuentes en el mundo. Las crisis epilépticas se consideran una manifestación clínica originada por una descarga excesiva de neuronas a nivel cerebral. Su prevalencia es mayor en Latinoamérica y el Caribe que en países desarrollados; las crisis, en la mayoría de los casos, corresponden a la epilepsia del lóbulo temporal, cuya anormalidad anatómica más habitual es la esclerosis del hipocampo. El objetivo es exponer el protocolo básico de epilepsia de manera estandarizada y su utilidad en el planeamiento quirúrgico, y así, conociendo todas las herramientas estudiadas hasta el momento, se realice un adecuado y oportuno diagnóstico. División de los temas tratados. Se realizó una revisión de tema de la literatura existente en las bases de datos Pubmed, Cochrane y Medline desde 1980 hasta 2018 acerca de la epilepsia del lóbulo temporal. Se expone de manera concisa la anatomía, fisiología, fisiopatología, presentación clínica y diagnóstico imaginológico de la patología. Conclusiones. Esta patología se caracteriza por tener el foco epileptogénico en los lóbulos temporales con alta probabilidad de control con técnicas quirúrgicas cada vez menos agresivas. El diagnóstico es inducido a través de la clínica; sin embargo, las nuevas técnicas de imagen estructurales y funcionales son el método diagnóstico de elección en pacientes con sospecha de esta patología y, de esta manera, lograr la realización de un diagnóstico más certero y oportuno. [Araujo-Reyes AT, Sandoval J, Carrasco-Ore A, Baquero-Serrano MA. Epilepsia del lóbulo temporal: una revisión de tema sobre el abordaje diagnóstico. MedUNAB. 2019;22(2):228-241. doi:10.29375/01237047.3208] Introduction. According to the World Health Organization (WHO), epilepsy is one of the world’s most frequent neurological disorders. Epileptic seizures are considered to be a clinical manifestation caused by an excessive discharge of neurons in the brain. Its prevalence is higher in Latin America and the Caribbean than in developed countries. In most cases, seizures correspond to temporal lobe epilepsy, whose most common anatomic abnormality is hippocampal sclerosis. The objective is to present the basic epilepsy protocol in a standardized form and its usefulness in surgical planning, in order to perform a correct and timely diagnosis, knowing all of the tools that have been studied until now. Division of Covered Topics. A topic review of the existing literature in the Pubmed, Cochrane and Medline databases from 1980 to 2018 was performed on temporal lobe epilepsy. The anatomy, physiology, physiopathology, clinical presentation and imaging diagnosis of the pathology are concisely presented. Conclusions. This pathology is characterized by having an epileptogenic focus in the temporal lobes, with a high probability of control with surgical techniques that are becoming less aggressive. Diagnoses are made through clinics. However, new structural and functional imaging techniques are the diagnosis method of choice for patients suspected to have this pathology in order to make a more accurate and timely diagnosis.

Esophagitis dissecans (ESD) is an uncommon disease that is associated with eosinophilic esophagitis (EoE), candidiasis and/or drugs. We aim to characterize the clinical, endoscopic and histological damage of the mucosal in subjects with dysphagia, its relation to concomitant entities and the treatment response. This is a retrospective observational study in patients with dysphagia and esophageal mucosal damage We included 23 patients (mean age = 55 years) who had GERD symptoms, dysphagia and/or odynophagia. There were 10, 9 and 4 cases of esophagitis dissecans, desquamative/esfacelante (ESD/ES) and fibrostenotic, respectively. ESD/SE is a rare entity with variable clinical, endoscopic and histological spectrum. The association with GERD was frequent.

Background:Plasmablastic lymphoma (PBL) is an aggressive lymphoma associated mainly to HIV infection, although cases in immunocompetent patients are described as well. Objective:To describe the clinicopathologic features and determine the overall survival of lymphoma patients according human immunodeficiency virus (HIV) status in Peruvian patients. Methods:We reviewed the pathology databases of 2 cancer centers and a general hospital from Peru. Forty cases were documented between 2005 and 2020. Categorical variables were compared using Fisher's exact test. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Statistical analysis was based on SPSS Program version 23. All cases were reviewed by two pathologists. Results:32 patients (80%) were HIV-positive. The median age for the whole cohort was 40 years (range, 22-86). The median age for HIV-positive and HIV-negative PBL patients were 37 years (range 22-67 years) and 57 years (range 27-86 years), respectively. The proportion of patients ≥60 years was lower in HIV-positive than in HIV-negative patients (8% and 37%, respectively; p= 0.046). 80% of patients in the whole cohort were female, and 84% and 62% in the HIV-positive and HIV-negative group, respectively. Extra-oral primary sites were the most frequent primary sites in both groups (66% and 88%, respectively). There were no statistically significant differences in Ann Arbor stage, Ki-67 expression, LDH levels, IPI scores, albumin levels, and neutrophil/lymphocyte ratio between HIV-positive and HIV-negative patients. All cases showed large lymphoid cells, of plasmablastic morphology with expression of at least one plasma cell marker (CD138, CD38, MUM1), CD45 positivity, variable expression of EMA, CD79 and CD30 and absence of expression of CD20, CD3, CD68 and LMP1; the proliferative index Ki67 varied between 60 and 90%. A small proportion of patients (18%) did not receive chemotherapy because of poor performance status or a personal decision. DA-EPOCH regimen was used in 52% and 25% of HIV+ and HIV- patients, respectively and CHOP/CHOEP regimen in 48 % and 75%, respectively. The overall response rate was 68% and 57% in HIV+ and HIV- patients with complete response (CR) in 32% and 14%, respectively. In the HIV-positive group, 66% of patients were antiretroviral therapy (ART)-naïve. The median progression-free survival (PFS) was 38 months and 7 months for HIV+ and HIV- patients, and the 1-year PFS was 74% and 0%, respectively. The median overall survival (OS) was 43 months (range 0.2-86.5) in HIV-positive patients and 10 months (range 0.5-19.0 months) in HIV-negative patients and the 1-year OS were 59% y 38%, respectively (p=0.27). Conclusions: PBL is a rare lymphoma, specially, if not related to HIV infection. In this study, 60 years or older was the only variable that showed significant difference. In our cohort, HIV-positive patients had better prognosis than HIV-negative PBL patients. Disclosures No relevant conflicts of interest to declare.

Childhood AML represents 15% of leukemias and is the most difficult cancer to treat due to its heterogeneity, high relapse rate, extramedullary disease, mortality related to chemotoxicity, and associated infections. We have the challenge of facing difficulties of health access and basal nutrition status. This is a cohort of 49 consecutive AML cases at INSN-SB in Lima-Peru from January 2014 to May 2020. We excluded Down's syndrome AML and patients who did not receive any chemotherapy treatment because they were critically ill at the time of diagnosis. Among the 49 cases, we analyzed 36 intention-to-treat cases under the BFM 2004 protocol according stratification risk. The median age was 5.7 years (range 0.4–15,7), F/M ratio 3/2, median time from initial symptoms to admission was 28 days (range 5–60), and 66.7% came from remote provinces. We classified as standard risk 25%, high risk 22.2%, and very high risk 52.8%. According to basal nutritional status, 30.6% of children had weight-based malnutrition and 19.4% had protein malnutrition. The transcription factor AML1-ETO was detected in 25% and 38.5% together with granulocytic sarcoma. We detected abnormal karyotype in 19 (52.8%), diploid in 14 (38.9%), and not available in 3 cases (8.3%). Median LDH was 1016 UI/dL (range 81–5453) for all the cohort but 3 cases. Complete response (CR) rate after induction was 55.6%; among the 20 response cases, 9 relapsed Eight cases underwent allogenic bone marrow transplantation (BMT) after induction therapy, of whom 3 relapsed. Induction response was higher for those younger than 5.7 years old (X2=5.4 p=0.05) and AML1-ETO detected cases (X2=4.56, p=0.064). Overall survival (OS) was 16.23±6.12 months for the entire analyzed cohort, and median disease-free survival (DFS) was 58.93±25.07 months for the CR group. DFS was not influenced by any of the variables studied. OS was higher for the BMT group (45.8±9.6 vs 21.2±4.8; log rank 4.107, p=0.043). Our cohort showed a low CR rate with high relapse rate, and it appears that induction followed by BMT assures higher OS.

OBJECTIVEThe aims of the study were to assess whether the Spanish version of the Hydrocephalus Outcome Questionnaire (HOQ) could be useful for the evaluation and comparison of outcomes in the patients in the authors’ region with those in patients in other institutions and to analyze predictors of functional outcome in patients with a shunt.METHODSThe authors performed this cross-sectional study between March 2015 and April 2016. All the parents of a pediatric patient with hydrocephalus who attended the Hospital Regional Universitario de Málaga neurosurgery outpatient clinic were invited to enroll in the study and complete the HOQ–Spanish version. Age at diagnosis and at the time of the study, clinical data, shunt complications, and socioeconomic factors were also recorded. A descriptive analysis was performed, and independent variables related to the HOQ scores were studied.RESULTSA total of 132 patients participated in the study (100% participation rate). The mean ages were 16.74 months (range 0–142 months) at diagnosis and 10.45 years (range 5–16 years) at the time of the study. The mean overall HOQ score was 0.68 (on a scale from 0 [worse] to 1.0 [best]). Factors related to a worse quality of life were seizures, motor or visual impairment, shunt infection, need for shunt revision, need for more than 2 shunt revisions (range 0–8 revisions), symptomatic overdrainage, and older age at the time of the study.CONCLUSIONSThe HOQ–Spanish version is useful in the authors’ region; the dimension scores found in this study were comparable to those previously reported by referral centers. Future goals should be to prevent shunt complications, routinely get children to reach functional status, and refer patients for adjuvant therapy promptly.

Rhinoliquorrhoea suggests a communication between the subarachnoid space and the sinonasal tract. Clinical presentation includes clear nasal discharge, headache, pneumocephalus, meningitis or brain abscess. Cerebrospinal fluid (CSF) leaks are mostly of traumatic origin (skull base fractures), iatrogenic (secondary to endoscopic endonasal surgery) or associated with tumour aetiology. Occasionally, hydrocephalus has been the cause of rhinoliquorrhoea in adults, presumably secondary to the chronically raised intracranial pressure with skull base erosion and meningocele. To our knowledge, the association of hydrocephalus and ethmoid meningoencephalocele/CSF leak has not been previously reported in a newborn child. We present the case of a 9-month-old girl who was referred for rhinorrhoea. She had a history of posthaemorrhagic ventricular dilatation. Brain computed tomography (CT) and magnetic resonance imaging (MRI) showed a left ethmoidal meningoencephalocele and small ventricular size. The meningoencephalocele was surgically repaired using an intradural subfrontal approach. During the postoperative period, after the transient lumbar drain was withdrawn, she developed symptomatic hydrocephalus. Ventriculoperitoneal shunting was required. Progressive ventricular dilatation may arise from a meningoencephalocele/CSF leak in paediatric patients. Early identification and repair of the meningoencephalocele are critical to avoid development of complications.

We report the case of a 44-year-old male, lacking clinical history of previous illness, who had surgery at our hospital to treat a mass in the supraclavicular space. The patient presented with a 1-month progressive distal paresis of the left arm. The histo-pathological examination of the mass revealed an encapsulated fat necrosis. Fat necrosis is characterised by cystic architecture, encapsulation with fat necrosis within, and inflammatory infiltration of its walls. Neural structure compression secondary to this tumour mass is very rare. Fat necrosis is more frequent in the lower limbs, in areas exposed to trauma. This article is the first report of brachial plexus compression due to supraclavicular fat necrosis.

11067 Background: GEIS 30 was a phase II study showing moderate activity of pazopanib in well-differentiated/dedifferentiated LPS (cohort A:37 pts, Progression free Survival (PFS) at 12 weeks (w) 43.2%) and no activity in Myxoid/round cell LPS (cohort B: 15 pts, PFS at 12w 13.3%). The present study aims to identify tumor and plasma biomarkers that are differently expressed in long responders (LRs) PFS > 24 w. Methods: Serum samples and paraffin-blocks at diagnosis were collected for 28 pts in cohort A and 11 in B. A total of 13 pts were LRs. Serum samples were obtained at baseline, after 3 w of treatment and at progression. A panel of 15 cytokines and growth factors were evaluated using Luminex technology (Millipore). Paraffin-blocks were evaluated for microvessel density (MVD) by CD31 immunostaining and Image Pro-Plus 7.0 Image Analysis System (Media-Cybernetics). For RNA expression analysis, the Oncology Biomarker Panel with probes for 2559 transcripts was used (HTG Molecular Diagnostics). Results: Serum cytokines showed that expression of angiopoietin (AGO) and BMP9 decreases during treatment, whereas GCSF increases. In addition, AGO and BMP overexpression at baseline was associated with worse prognosis in arm A (p = 0.09) and B (p = 0.01) respectively. No differences between study arms and outcome were appreciated by MVD. Gene expression revealed differences in some immunomodulators: PDL-1 was correlated with serum cytokines VEGFD (p = 0.04) and LEPTIN (p = 0.02); and PD-1 with VEGFD (p = 0.04), LEPTIN (p = 0.02), VEGFA (p = 0.02) and ANGIO (p = 0.03). PD1, in addition,was overexpressed in LRs (p = 0.05). Interestingly, three groups were identified in cohort A according to gene expression: Cluster 1, characterized by short-responder patients with the shortest overall survival, whereas cluster 3 (40% LRs) and 2 (63.6% LRs) showed longer survival rates (14.3%, 45.5% and 30% respectively) (p = 0.001). Conclusions: Gene expression profiling unveils three WD/DD-LPS biotypes according to their response to pazopanib, which could be potentially used to select pts for treatment

The diagnostic criteria and management of this condition continue to be a topic of debate in the literature. The term definitive symptomatic LOVA (longstanding overt ventriculomegaly in adults) is applied to patients that fulfil a series of diagnostic criteria,which are reviewed in our paper. The main subject of our study is to propose a rearrangement of the criteria for the diagnosis of this entity and adjusted treatment strategies. We present our data evaluating the role of endoscopy in this pathology. This descriptive and analytical study comprised 27 adult patients with LOVA who underwent endoscopic third ventriculostomy (ETV). Data regarding age, gender and onset of symptoms, a previously implanted shunt, clinical examination and radiological findings at the time of diagnosis, and the intracranial pressure (ICP) recordings in some cases, were carefully retrospectively reviewed. ETV success was determined based on clinical state and radiological criteria. ETV was performed in all 27 cases. Mean follow up period was 4.2 years (6 months to 8 years). 2/27 patients (7.40%) were lost to follow-up. The overall success rate for ETV was 76% (21/25 patients). ETV resulted in shunt independency in two of the three patients with a previous shunt. Based on our results, we believe that ETV must be considered as the treatment of choice for patients with symptomatic LOVA.

Cell therapy is an evolving option for patients with end-stage heart failure. First-generation cell therapy trials have had marginal success. Our goal was to evaluate retrograde delivery of allogeneic umbilical cord subepithelial cells (UCSECs) in patients with heart failure. A prospective open-label dose escalation study of the safety and feasibility of UCSECs infused retrogradely into the coronary sinus was performed. Patients received a single dose of either 100 million (M), 200M, or 400M cells. The patients were followed for 2 years. Twenty-four patients were successfully enrolled in the study. The patients had UCSEC infusion without procedure-related complications. The ejection fraction in patients receiving UCSECs demonstrated improvement compared to baseline; from 25.4% (±5.5) at screening to 34.9% (±4.1) at 12 months. End-systolic diameter decreased significantly from 59.9 (±5.3) mm to 52.6 (±2.7) mm ( p < 0.05). Retrograde UCSEC delivery was safe and feasible in all three dosage groups. Patients receiving 200M and 400M UCSECs showed signs of early improvement in left ventricular ejection fraction (LVEF) and remodeling. This study provides the basis for a larger clinical trial in heart failure (HF) patients using the middle or high dose of UCSECs.

Surgical outcome after shunt insertion in pediatric hydrocephalus can vary greatly. Although first shunt survival rates and complications have been studied by several teams, much less is known about survival and complications of subsequent systems. The goals of this study were to evaluate the surgical outcome in a series of pediatric patients followed for a long time and establish the differences between first and subsequent extracranial shunt survival and complications. We undertook a retrospective study in pediatric patients treated with ventriculoperitoneal shunts between 2000 and 2015 at our institution. Surgical outcome was assessed, and different shunt survival curves were studied with Kaplan-Meier. Complications related to each shunt failure were examined and compared. A total of 166 patients underwent 425 procedures, with a mean follow-up period of 93 months. The median number of shunt revision surgeries was 2. Shunt survival rates were better with the first shunt compared to those with the subsequent shunts. The main complication necessitating system revision surgery was overdrainage, the frequency of proximal and distal dysfunctions was similar in all the shunt failures, and isolated ventricle and infection were more frequent in younger patients. Shunt-related infections accounted for 7 % of the procedures, and the shunt independence rate was 10 %. The frequency of complications related to shunt failure in pediatric patients changes during follow-up. A strict protocol of overdrainage detection and active treatment could explain the need for repeat surgeries and the progressively shorter shunt survival time in our series.

Purpose Doxorubicin and trabectedin are considered active drugs in soft tissue sarcoma (STS). The combination of both drugs was hypothesized to be advantageous and safe on the basis of preclinical evidence and a previous phase I trial, respectively. The aim of this study was to compare the clinical outcome of trabectedin plus doxorubicin with doxorubicin as first-line treatment of advanced STS patients. Patients and Methods In this open-label randomized phase II trial, the main end point was progression-free survival (PFS). Trabectedin 1.1 mg/m2 in a 3-hour infusion plus doxorubicin 60 mg/m2 as the experimental arm and doxorubicin 75 mg/m2 as the control arm were administered for up to six cycles. Translational research was planned to correlate the expression of apoptotic and DNA repair genes with clinical outcome. Results In 115 randomly assigned patients, the median PFS was 5.5 months in the control arm and 5.7 months in the experimental arm (hazard ratio, 1.16; 95% CI, 0.79 to 1.71; P = .45) in the intent-to-treat analysis. The trial was stopped for futility after the interim analysis, because the results in the experimental arm showed the risk reduction for the main end point to be < 9.64%. The proportion of patients with grade 3 or 4 thrombocytopenia, asthenia, and liver toxicity was significantly higher in the experimental arm. FAS and p53 were shown to be prognostic factors for PFS (7.0 months if FAS+ and p53−; 3.4 months if FAS+/p53+ or FAS−/p53−; and 0.7 months if FAS− and p53+; P < .001) and for overall survival. Conclusion Trabectedin plus doxorubicin did not show superiority over doxorubicin alone as first-line treatment of advanced STS. The prognostic role of apoptotic key genes, FAS and p53, was shown to be robust enough to continue this research line.

Purpose To assess the activity and toxicity of the combination of gemcitabine plus dacarbazine (DTIC) in patients with advanced soft tissue sarcoma (STS) in a randomized, multicenter, phase II study using DTIC alone as a control arm. Patients and Methods Patients with previously treated advanced STS were randomly assigned to receive either fixed-dose rate gemcitabine (10 mg/m2/min) at 1,800 mg/m2 followed by DTIC at 500 mg/m2 every 2 weeks, or DTIC alone at 1,200 mg/m2 every 3 weeks. The primary end point of the study was progression-free rate (PFR) at 3 months. Results From November 2005 to September 2008, 113 patients were included. PFR at 3 months was 56% for gemcitabine plus DTIC versus 37% for DTIC alone (P = .001). Median progression-free survival was 4.2 months versus 2 months (hazard ratio [HR], 0.58; 95% CI, 0.39 to 0.86; P = .005), and median overall survival was 16.8 months versus 8.2 months (HR, 0.56; 95% CI, 0.36 to 0.90; P = .014); both favored the arm of gemcitabine plus DTIC. Gemcitabine plus DTIC was also associated with a higher objective response or higher stable disease rate than was DTIC alone (49% v 25%; P = .009). Severe toxicities were uncommon, and treatment discontinuation for toxicity was rare. Granulocytopenia was the more common serious adverse event, but febrile neutropenia was uncommon. Asthenia, emesis, and stomatitis were the most frequent nonhematologic effects. Conclusion The combination of gemcitabine and DTIC is active and well tolerated in patients with STS, providing in this phase II randomized trial superior progression-free survival and overall survival than DTIC alone. This regimen constitutes a valuable therapeutic alternative for these patients.

We report one case of dermatomyositis and one of polymyositis refractory to several conventional inmunosupressive therapies, which present a response after treatment with rituximab, enabling steroid dose reduction and a prolonged remission.

Megestrol acetate is a synthetic progestin that has been used since the 1970s for the treatment of advanced cancer and subsequently to treat anorexia, cachexia and weight loss in AIDS patients. It has been shown that high doses or prolonged treatment with this drug may cause Cushing's syndrome, new-onset diabetes and suppression of plasma ACTH and cortisol levels. Megestrol acetate may cause suppression of the pituitary-adrenal axis due to the affinity of this compound for the glucocorticoid receptor. Recognising the glucocorticoid-like activity of megestrol and its effects at the axis level is important for the diagnosis of sub-clinical adrenal insufficiency. We present the case of a 74-year-old woman with infiltrating ductal breast carcinoma refractory to prolonged hormonal treatment with megestrol acetate, presenting with adrenal insufficiency.

Intraventricular hemorrhage is the most common cause of infantile acquired hydrocephalus. Our objective is to determine if the implantation of ventriculoperitoneal shunt in posthemorrhagic hydrocephalus as a primary and definitive neurosurgical treatment, with no previous temporary procedures, would decrease complication rates with good functional outcomes. Two hundred seventy-one patients with germinal matrix hemorrhage were diagnosed at the Carlos Haya Hospital between 2003 and 2010. Forty-seven patients underwent ventriculoperitoneal shunt after developing symptomatic hydrocephalus. The minimum weight required for shunt implantation was 1,500 g. We recorded complications related to the surgical procedure and analyzed functional state with a self-developed four-grade scale. One hundred thirty-nine (51.3 %) patients with intraventricular hemorrhage developed ventricular dilatation, but only 47 patients (17.34 %) needed shunting. In seven cases, temporary neurosurgical procedures were performed, but in all of them, this was followed by ventriculoperitoneal shunt implantation. The infection rate was 4.25 %, and shunt obstruction rate was 4.25 %. More than 80 % of patients were classified as good or excellent functional state. Mean follow-up period was 38.75 months (SD, 27.09; range, 1–102 months). Ventriculoperitoneal shunting as a primary neurosurgical treatment in posthemorrhagic hydrocephalus would decrease surgical morbidity with good functional outcome.

11039Background: Pazopanib, a multitarget TKI, has been approved as second or later line treatment for advanced non-adipocytic soft-tissue sarcoma. This open-label, phase II clinical trial was desi...

Background Chronic refractory angina is a challenging clinical problem with limited treatment options. The results of early cardiovascular stem cell trials using ABMMC have been promising but have utilized intracoronary or intramyocardial delivery. The goal of the study was to evaluate the safety and early efficacy of autologous bone marrow derived mononuclear cells (ABMMC) delivered via percutaneous retrograde coronary sinus perfusion (PRCSP) to treat chronic refractory angina (CRA). Methods From May 2005 to October 2006, 14 patients, age 68 +/- 20 years old, with CRA and ischemic stress-induced myocardial segments assessed by SPECT received a median 8.19*108 ± 4.3*108 mononuclear and 1.65*107 ± 1.42*107 CD34+ cells by PRCSP.. Results ABMMC delivery was successful in all patients with no arrhythmias, elevated cardiac enzymes or complications related to the delivery. All but one patient improved by at least one Canadian Cardiovascular Society class at 2 year follow-up compared to baseline (p < 0.001). The median baseline area of ischemic myocardium by SPECT of 38.2% was reduced to 26.5% at one year and 23.5% at two years (p = 0.001). The median rest left ventricular ejection fraction by SPECT at baseline was 31.2% and improved to 35.5% at 2 year follow up (p = 0.019). Conclusions PRCSP should be considered as an alternative method of delivery for cell therapy with the ability to safely deliver large number of cells regardless of coronary anatomy, valvular disease or myocardial dysfunction. The clinical improvement in angina, myocardial perfusion and function in this phase 1 study is encouraging and needs to be confirmed in randomized placebo controlled trials.

More than a million HCT have been performed worldwide to date, but transplant rates and indications vary widely across regions. The Latin American Bone Marrow Transplantation Group (LABMT) was created under the auspices of the Worldwide Network for Blood and Marrow Transplantation (WBMT) in 2011 to assist in diffusing the practice, to integrate centers from multiple countries and to improve access to transplantation in the region. To evaluate the actual HCT activity, trends and contemporary practices in Latin America (LA), the LABMT surveyed centers for the annual activity from 2009 to 2012. Methods: The WBMT Global Activity Survey was used as a template and sent to all Hematology and HCT Societies in the region. This survey includes information of annual HCT numbers by center, indications, stem cell source and donor type. Results: A total of 11,116 HCT were performed between 2009 and 2012 with an increase in annual numbers from 2,517 in 2009 to 3,072 in 2012 (22%). The majority of the HCT were autologous (62%) with a 32% increase in activity over the period analyzed. In contrast, the increase in allogeneic HCT (6%) was relatively small. The majority of allogeneic HCT used related donors (n=3210), mostly HLA-identical peripheral blood (n=1812), bone marrow (n=1128) and non-identical related peripheral blood (n=156). Unrelated donor HCT (n=982) were performed mostly using cord blood (n=427), followed by bone marrow (n=332) and peripheral blood (n=223). In 2012, 91 teams from 12 countries reported 3,072 patients. Transplant rates (TR; HCT/10 million population) were 21 for allogeneic (ranging from 6 in Venezuela to 85 in Uruguay) and 60 for autologous HCT (ranging from 8 in Mexico to 215 in Uruguay). Unrelated donor TR was 5, ranging from 0 (Costa Rica, Panama, Peru, Paraguay and Venezuela) to 18 (Chile). Transplant center team density (team/10 million inhabitants) was 1.8 in 2012, with the highest in Uruguay (15), followed by Panama (8), Costa Rica (4), and Argentina (4). In comparison to other regions, transplant center density in LA was identical to the Asian Pacific region and lower than in Europe (7) or US/Canada (6). TR in LA compared to Asia/Pacific were higher for autologous (39 vs. 14) and lower for allogeneic (21 vs. 24, respectively, Table 1). Most transplant indications for autologous HCT (65% of all HCT) were plasma cell disorders (48%) and lymphomas (41%). Most allogeneic transplants (35% of all HCT) were performed for acute leukemias (58%, equally myeloid and lymphoid leukemias) and 18% for non-malignant disorders. Conclusion: While transplant indications are comparable to HCT performed in Europe and North America, transplant rates, transplant center and transplant team densities in LA are markedly lower. More autologous than allogeneic HCT are performed and autologous HCT increased considerably between 2009 and 2012. Unrelated donor TR is lower than in other regions. Initiatives are currently being taken to increase transplant activity, especially using alternative donor transplants within the region. Table 1. Transplant Rates and Team Density Worldwide Transplant rates (HCT/10 million population) Team density Region POP TOTAL AUTO ALLO FAMILY SIBLING UNRELATED LA 511.7 60.0 39.2 20.9 16.0 14.3 4.9 1.8 SEAR/WPR 3078.0 38.6 14.2 24.4 12.5 8.2 11.9 1.8 EUROPE 846.4 379.3 222.5 156.8 68.2 57.0 88.6 7.6 USA/Canada 348.0 482.5 264.9 217.5 91.2 75.8 126.3 6.2 EMR/AFR 690.9 29.8 12.7 17.2 15.7 15.0 1.4 0.4 HCT, hematopoietic cell transplantation; POP, population; AUTO, autologous; ALLO, allogeneic; SEAR/WPR, South East Asia/Western Pacific Region; LA, Latin America; EMR/AFR; Eastern Mediterranean/African Region Disclosures No relevant conflicts of interest to declare.

Learning ObjectivesAfter completing this course, the reader will be able to: Discuss the clinical manifestations of myelofibrosis with myeloid metaplasia and recent developments in the understanding of its pathogenesis.Discuss the most recent clinical trials involving novel therapies for myelofibrosis with myeloid metaplasia.Propose an algorithm-based approach to the treatment of patients with myelofibrosis with myeloid metaplasia.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.comThe molecular basis of chronic idiopathic myelofibrosis (CIMF) has remained elusive, thus hampering the development of effective targeted therapies. However, significant progress regarding the molecular mechanisms involved in the pathogenes is of this disease has been made in recent years that will likely provide ample opportunity for the investigation of novel therapeutic approaches. At the fore front of these advances is the discovery that 35%–55% of patients with CIMF harbor mutations in the Janus kinase 2 tyrosine kinase gene. Until very recently, the management of patients with CIMF involved the use of supportive measures, including growth factors, transfusions, or interferon, and the administration of cyto-reductive agents, such as hydroxyurea and anagrelide. However, several trials have demonstrated the efficacy of antiangiogenic agents alone or in combination with corticosteroids. In addition, the use of reduced-intensity conditioning allogeneic stem cell transplantation has resulted in prolonged survival and lower transplant-related mortality.

Hemorrhagic cystitis (HC) remains a common complication of allogeneic blood and marrow transplantation. Previous analyses of risk factors for this complication were performed in heterogenous populations, with dissimilar diagnosis and conditioning regimens. We postulated that HC is more prevalent in matched unrelated donor (MUD) and unrelated cord blood (UCB) transplantations than in matched related donor (MRD) transplantations. We performed a retrospective study on 105 acute lymphocytic leukemia patients treated with 12 Gy total body irradiation-based regimens and allogeneic transplants (MUD, n = 38; UCB, n = 15; mismatched related, n = 20; MRD, n = 32). HC occurred in 16% of patients receiving MRD transplants, 30% of recipients of mismatched related, and 40% of MUD or UCB transplants (hazard ratio 2.9, 95% CI 1.0-7.9 for the comparison of MRD versus MUD). The excessive rate of HC among MUD and UCB patients became evident after the first 30 days after transplantation. Recipients younger than 26 years had a significantly higher incidence of HC (HR 2.5, 95% CI 1.1-5.8). This donor type and age effect was independent of platelet engraftment, development of graft-versus-host disease (GVHD), source of stem cells, use of anti-thymocyte globulin (ATG) or cyclophosphamide in the regimen, steroid use, or stem cell source. We concluded that HC is more prevalent in MUD and UCB transplantations. (Blood. 2004;103:4674-4680)

BACKGROUND: Recent studies have shown a correlation between diffuse large B-cell lymphoma (DLCBL) prognosis and molecular features using genome profiles by cDNA microarrays. Later reports have shown that immunohistochemical tests using markers as CD10, bcl-6 and MUM-1 to identify germinal center B-cell (GCB) and non-GCB patterns can have a similar value and are gaining major importance in assessing prognosis in patients with DLBCL. Gastric DLCBL is the most frequent extranodal non-Hodgkin lymphoma. AIM: To evaluate the frequency of GCB and non-GCB subgroups in primary gastric DLCBL and the impact of these tests in prognosis. PATIENTS AND METHODS: Patients older than 18 years with a diagnosis of primary gastric DLBCL were identified in a single institution from January 2002 to December 2005 and included in this analysis. Immunohistochemical stains were performed using antibodies against CD20, CD10, bcl-6 and MUM1 in all cases. Survival curves were obtained using the Kaplan-Meier method. RESULTS: Twenty-nine patients were included in this study. The median age at diagnosis was 68 years (range 40 to 86 years). Thirteen male and 16 female patients were included. All cases received chemotherapy with CHOP regimen. Cases were subclassified in GCB and non-GCB using CD10, bcl-6, and MUM1 expression. Four cases (14%) were considered GCB and 25 cases (86%) non-GCB. There were no statistical differences between both groups in the following variables: age, ECOG performance status, serum LDH levels, clinical stage and International Prognostic Index (IPI) score. No statistical difference in survival was observed between the GCB and non-GCB groups. The 3-year overall survival for the entire group was 30%. CONCLUSION: Immunohistochemical expression of non-GCB pattern is very frequent in primary gastric DLBCL in Peru. However, it does not show an effect in survival, probably related to the small number of cases included in the present study.

Background: 90Y-ibritumomab tiuxetan (Zevamab®; ZEV; Bayer-Schering Pharma- Argentina) has been approved for the treatment of relapsed, refractory and transformed (high grade) follicular lymphomas. Methods: Between Sep. 2005 and Feb. 2008, 45 patients (pts) [22 F & 23 M; median age 62 yrs (45–83)] with refractory/relapsed lymphoma were enrolled. Diagnoses: 37 follicular lymphoma (FL), 5 were mantle cell lymphoma (ML) and 3 transformed lymphoma (TL); 18 pts had bulky disease, 8 had bone marrow involvement and 21 had stage III–IV disease. Median time from diagnosis was 5 yrs (0.5– 29). Twenty two pts had received 1–2 previous treatments, and 23 pts had received 3–5 previous treatments including 5 pts with autologous bone marrow transplantation. All had previously received anti-CD20 monoclonal antibody therapy. Six pts received previous radiotherapy. ZEV was administered at 0.3 or 0.4 mCi, based on initial platelet count. Seven days before, and the same day of the ZEV administration, pts received standard rituximab 250 mg/m2. In 3 pt, ZEV was part of the conditioning regimen of autologous bone marrow transplantation. Results: Forty pts were evaluable for response: 34 (86%) pts responded – 19 CR (48%), 15 PR (38%). Overall survival and PFS for the entire group at 18 months was 63% and 37% respectively, with a median follow-up of 12 months (1–29 months). Of the 45 patients, 5 pts (11%) had died before third month and response was not assessed, 6 pts (13%) did not respond, 3 (7%) died with response from other causes, 14 pts (31%) responded and subsequently relapsed. Finally 17 pts (38%) continue to be in response, 9 (20%) lasting more than twelve months (long lasting responders). Slight differences in duration of response and survival were observed between FL vs ML and TL favouring FL (RR 2.047). Forty six per cent of pts required filgrastim for neutropenia, 24% required platelet transfusions, 22% had neutropenia plus fever and were admitted for complicated pancytopenia, and 20% required red blood cells transfusion. Two patient died 30 & 40 days after treatment with hypoplastic bone marrow complicated with sepsis in the post autologous bone marrow transplantation period. Four pts with previous bone marrow transplantation required filgrastim, transfusions and 2/3 had febrile neutropenia. Conclusion: Our experience with ZEV in relapsed and refractory FL shows 48 % CR. Even heavily treated pts that had previous bone marrow transplantation were able to receive ZEV, although they required extra support. Our experience supports the use of ZEV in relapsed and refractory lymphomas even after autologous bone marrow transplantation.

BACKGROUND: Epstein-Barr vitus (EBV)-positive status is related to a poor survival in patients with Hodgkin lymphoma, T-cell non-Hodgkin lymphoma (NHL) and, in a recent publication from Asia, in patients with diffuse large B-cell lymphoma (DLBCL). AIM: In order to define the impact of EBV infection on survival in patients with nodal DLBCL, we investigated the EBV status in elderly Peruvian patients with a diagnosis of DLBCL. PATIENTS AND METHODS: Between January 2002 and December 2004, thirty-eight patients older than 70 years who were diagnosed with nodal DLBCL were included in the analysis. Clinical data were reviewed retrospectively from the patients’ records. Nodal tissue from all cases was analyzed for the presence of EBV encoded RNA (EBER) using the in situ hybridization (ISH) method. Survival analysis was performed using the Kaplan-Meier method. RESULTS: Eight cases (21%) were identified as EBV-positive; the remaining 30 cases (79%) were EBV-negative. Within clinical characteristics, EBV-positivity was associated with poorer performance status, more advanced stage and higher IPI scores. From the 8 EBV-positive cases, two cases (25%) had a germinal center (GC)-like phenotype, whereas the other six (75%) had a non-germinal center phenotype. Overall survival for EBV-positive DLBCL patients was 0.5 months and for EBV-negative patients was 14 months (p = 0.002). In the multivariate analysis, EBV status emerged as an independent variable for survival when evaluated against the IPI score (p = 0.001). There were no differences in survival between DLBCL phenotype (GC versus non-GC). CONCLUSION: EBV status in elderly patients with nodal DLBCL is a powerful survival prognostic factor and its role in the survival of other lymphoproliferative disorders and age groups should be investigated. New therapeutic strategies should be defined in patients with EBV-positive DLBCL.

The radionucleid conjugate with monoclonal antibodies (antiCD20/90Y-ibritumomab tiuxetan) have been approved for the treatment of relapsed, refractory and transformed (high grade) follicular lymphomas. Between September 2005 and August 2007, 41 patients with refractory/relapsed lymphoma were enrolled. Median age was 62 yrs old (45–83). Twenty were women and 21 were men. Thirty three were follicular and 5 were mantle cell lymphoma and 3 transformed lymphoma. Eighteen patients had bulky disease, 8 had bone marrow involvement and 21 had stage III-IV disease. Median time from diagnosis was 5 years (0.5–29). Twenty one had received 1–2 previous treatments, and 20 pts had received 3–5 previous treatments including 5 pts with autologous bone marrow transplantation. All had previously received anti-CD20 monoclonal antibody therapy. Six pts received previous radiotherapy. 90Y-Ibritumomab (Zevamab™ Bayer-Schering Argentina) was administered at 0.3 or 0.4 mCi, based on initial platelet count. Seven days before, and on the same day of the immunoconjugate administration, pts received rituximab 250 mg/m2. Thirty eight were evaluable for response. Thirty four (89%) pts responded: 20 CR (53%) and 14 PR (36%). With a median follow-up of 10 months, 60% of pts were expected to continue in CR at 18 months. Overall survival at the same period for the entire group was 89%. Nineteen pts (46%) required filgrastim administration for neutropenia, Ten pts (24%) required platelet transfusions, 10 pts had neutropenia plus fever and they had to be admitted for complicated pancytopenia, 8 pts required red blood cells transfusion. Two patient died 30 and 40 days after treatment with hypoplastic bone marrow complicated with septicemia and in the post autologous bone marrow transplantation period, respectively. Four pts with previous bone marrow transplantation, required filgrastim, transfusions and 2/3 had febrile neutropenia. Our experience with 90Y-ibritumomab in relapsed and refractory folicullar lymphoma shows 53% CR. Even heavily treated pts, that had previous bone marrow transplantation were able to receive the radioimmunoconjugate, although they required extra support. Our experience favours the use of 90Y-Ibritumomab tiuxetan in relapsed and refractory lymphomas even if they had received previous autologous bone marrow transplantation.