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The number of patients with bone metastasis increases as medical management and surgery improve the overall survival of patients with cancer. Bone metastasis can cause skeletal complications, including bone pain, pathological fractures, spinal cord or nerve root compression, and hypercalcemia. Before initiation of treatment for bone metastasis, it is important to exclude primary bone malignancy, which would require a completely different therapeutic approach. It is essential to select surgical methods considering the patient’s prognosis, quality of life, postoperative function, and risk of postoperative complications. Therefore, bone metastasis treatment requires a multidisciplinary team approach, including radiologists, oncologists, and orthopedic surgeons. Recently, many novel palliative treatment options have emerged for bone metastases, such as stereotactic body radiation therapy, radiopharmaceuticals, vertebroplasty, minimally invasive spine stabilization with percutaneous pedicle screws, acetabuloplasty, embolization, thermal ablation techniques, electrochemotherapy, and high-intensity focused ultrasound. These techniques are beneficial for patients who may not benefit from surgery or radiotherapy. [ABSTRACT FROM AUTHOR]

Chronic myeloid leukemia (CML) is characterized by the constitutive tyrosine kinase activity of the oncoprotein BCR-ABL1 in myeloid progenitor cells that activates multiple signal transduction pathways leading to the leukemic phenotype. The tyrosine-kinase inhibitor (TKI) nilotinib inhibits the tyrosine kinase activity of BCR-ABL1 in CML patients. Despite the success of nilotinib treatment in patients with chronic-phase (CP) CML, a population of Philadelphia-positive (Ph+) quiescent stem cells escapes the drug activity and can lead to drug resistance. The molecular mechanism by which these quiescent cells remain insensitive is poorly understood. The aim of this study was to compare the gene expression profiling (GEP) of bone marrow (BM) CD34+/lin- cells from CP-CML patients at diagnosis and after 12 months of nilotinib treatment by microarray, in order to identify gene expression changes and the dysregulation of pathways due to nilotinib action. We selected BM CD34+/lin- cells from 78 CP-CML patients at diagnosis and after 12 months of first-line nilotinib therapy and microarray analysis was performed. GEP bioinformatic analyses identified 2,959 differently expressed probes and functional clustering determined some significantly enriched pathways between diagnosis and 12 months of nilotinib treatment. Among these pathways, we observed the under expression of 26 genes encoding proteins belonging to the cell cycle after 12 months of nilotinib treatment which led to the up-regulation of chromosome replication, cell proliferation, DNA replication, and DNA damage checkpoint at diagnosis. We demonstrated the under expression of the ATP-binding cassette (ABC) transporters ABCC4, ABCC5, and ABCD3 encoding proteins which pumped drugs out of the cells after 12 months of nilotinib. Moreover, GEP data demonstrated the deregulation of genes involved in the JAK-STAT signaling pathway. The down-regulation of JAK2, IL7, STAM, PIK3CA, PTPN11, RAF1, and SOS1 key genes after 12 months of nilotinib could demonstrate the up-regulation of cell cycle, proliferation and differentiation via MAPK and PI3K-AKT signaling pathways at diagnosis. [ABSTRACT FROM AUTHOR]

Summary: Optimal treatment for transformed follicular lymphoma (tFL) is not fully defined. Clinical characteristics and treatments that impact on post‐transformation outcome of 176 biopsy‐proven tFL were analysed. Transformation occurred at initial diagnosis in 52% (Group 1) and after a FL diagnosis in 48% (Group 2). Five‐year overall survival was 84% for Group 1 and 51% for Group 2 (P < 0·001). In Group 1, 5‐year progression‐free survival was superior after rituximab maintenance compared to observation only (94% vs. 53%, P = 0·024). In Group 2, an inverse trend was found between survival and both a higher number of pre‐transformation treatment lines and a short time‐to‐transformation. [ABSTRACT FROM AUTHOR]

The article talks about a study, focusing on the use of bortezomib to treat anemic patients who have relapsed cold agglutinin disease (CAD). Topics discussed include the anti–red blood cell immunoglobulin M (IgM) autoantibodies that cause CAD; the lack of effectiveness of corticosteroids and immunosuppressants in treating CAD; and the median hemoglobin levels of patients under study.

BACKGROUND: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder with heterogeneous biological and clinical features. The biomolecular mechanisms of CML response to tyrosine-kinase inhibitors are not fully defined. OBJECTIVE: We undertook a gene expression profiling (GEP) study of selected bone marrow (BM) CD34+/lin- cells of chronic-phase CML patients at diagnosis and after 12 months of TKI nilotinib to investigate molecular signatures characterizing both conditions. METHODS:We selected and counted BM CD34+/lin- cells of 30 CML patients at diagnosis and during 3, 6 and 12 months of first-line nilotinib treatment. GEP was performed between CD34+/lin- cells of patients at diagnosis and the same patients after 12 months of nilotinib. RESULTS: The number of BM CD34+/lin- cells dramatically decreased after 3, 6 and 12 months of nilotinib. GEP detected 264 statistically significant differentially expressed genes at diagnosis vs. 12 months of nilotinib. Functional enrichment analysis revealed groups of genes belonging to 14 pathways differentially active during nilotinib treatment. CONCLUSIONS: In conclusion, lipid, glucose and sphingolipid metabolism, insulin resistance, complement and coagulation, platelet activation, cytoscheleton, cell adhesion, transport, B cell differentiation, RAS-signaling pathway, proliferation, growth factors, and apoptosis were significantly deregulated between CML patients at diagnosis and after 12 months of nilotinib. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the outcome of selective arterial embolization with N-2-butyl-cyanoacrylate for aneurysmal bone cysts.Methods: We retrospectively studied 102 patients (72 male, 30 female; mean age, 16 years; range, 3-60 years) with aneurysmal bone cysts treated with embolization with N-2-butyl-cyanoacrylate. Mean follow-up was seven years (range, 3-13 years); no patient was lost to follow-up. We evaluated healing and recurrences of the lesions, complications and cost of the procedures, and recurrences with respect to age and gender of the patients, and size and location of the lesions.Results: Embolization was feasible in 88 patients (86.3%), and not feasible in 14 patients (13.6%) because feeding arteries were not identified or the spinal artery of Adamkiewicz was recognized at the embolization field. Seventy two patients (81.8%) experienced complete healing of their lesions after a single (50 patients, 56.8%), a second (17 patients, 19.3%) or a third embolization (5 patients, 5.7%). Sixteen patients (18.2%) experienced recurrence within four months (range, 3-9 months) after embolization; these patients underwent surgical treatment. Recurrences were more common in patients younger than 15 years of age and cysts larger than 6 cm, without any difference with respect to gender and location. Four patients (4.5%) experienced a complication including skin necrosis, sciatic nerve paresthesias, and femoral artery pseudoaneurysm. The cost estimate was 3000 euro per procedure.Conclusion: Embolization of aneurysmal bone cysts with N-2-butyl-cyanoacrylate is associated with good results and low complication rates, however, experience, technical skills, and knowledge of the vascular anatomy of the area is necessary. [ABSTRACT FROM AUTHOR]

Purpose: Deferiprone (DFP), deferasirox (DFX) and deferoxamine (DFO) are used in thalassaemia major (TM) patients to treat chronic iron overload. We evaluated the cost-effectiveness of DFP, compared with DFX and DFO monotherapy, from an Italian healthcare system perspective. Methods: A Markov model was used over a time horizon of 5 years. Italian-specific cost data were combined with Italian efficacy data. Costs and quality-adjusted life years (QALYs) were calculated for each treatment, with cost-effectiveness expressed as cost per QALY. Results: In all scenarios modelled, DFP was the dominant treatment strategy. Sensitivity analyses showed that DFP dominated the other treatments with a >99% likelihood of being cost-effective against DFX and DFO at a willingness to pay threshold of €20,000 per QALY. Conclusions: DFP was the dominant and most cost-effective treatment for managing chronic iron overload in TM patients. Its use can result in substantial cost savings for the Italian healthcare system. [ABSTRACT FROM AUTHOR]

Bone sarcomas are a variety of non-epithelial, malignant neoplasms of bone. The most common bone sarcomas are osteosarcoma, Ewing's sarcoma, and chondrosarcoma. The approach to a patient with a suspected bone sarcoma from initial examination to the histological diagnosis and classification is staging. Staging is of critical importance, in order to classify different treatment options and point out which combination of them is more suitable depending on the severity of the tumor in every individual patient. Staging should include medical history, physical and imaging examination, and biopsy. This article presents the current approach for staging, principles of biopsy, tumor classification, treatment, and follow-up of patients with bone sarcomas. [ABSTRACT FROM AUTHOR]

Background: The prognosis of patients with metastatic, recurrent, and/or unresectable osteosarcoma is poor. Aggressive local and medical treatments are available for palliation. Palliative treatments include isolated limb perfusion, radiation therapy, embolization, chemoembolization, thermal ablation, and cryoablation. Their aim is pain relief and tumor size reduction with minimum complications. Materials and methods: We present 19 patients with metastatic, recurrent, and/or unresectable osteosarcoma of the pelvis and lower lumbar spine treated with palliative selective embolization using N-2-butyl cyanoacrylate. All patients had chemotherapy. At the time of embolization, they experienced severe pain refractory to analgesics. Diagnostic angiography was performed pre-embolization to determine the vascular mapping and hemodynamic status of the tumor. Post-embolization angiography was done to evaluate for complete occlusion of the pathological vessels. Mean follow-up was 18 months. Local pain, tumor necrosis and size, and complications were recorded. Results: In all patients, pre-embolization angiography showed hypervascularity of the tumor from extensive neovascularization. Five patients had repeat embolization. All patients experienced pain relief at a mean of 3 days post-embolization. No patient had recurrent pain with the intensity of that before embolization. Variable tumor necrosis was observed in follow-up imaging, and reduction in tumor size was minimum. All patients experienced pain at the site of embolization, which resolved completely 1-5 days after embolization. Four patients with pelvic osteosarcomas experienced paraesthesias at the distribution of the sciatic nerve. Conclusion: Selective arterial embolization is a useful local palliative treatment for patients with advanced osteosarcoma for pain relief. [ABSTRACT FROM AUTHOR]

Abstract: This study clarifies the relationship between clinical and laboratory patterns, in endocrine-responsive metastatic breast cancer patients treated with a cyclic beta-interferon and interleukin-2 sequence added to anti-estrogens. In 31 patients, a regular laboratory and immunological assessment was made. During clinical benefit, as opposed to progression, a significant increase in the total number of lymphocytes, CD4+, CD8+, NK cells, CRP and IL-12 was confirmed. Also, a significant CEA, TPA, CA15.3 decrease occurred 24–72h after interleukin-2 administration. At the progression, both basally and after interleukin-2 stimulation, the mean values of CD4+ plus CD25+ cells were more than twice higher than during clinical benefit, with a decrease of CD4+ plus CD8+ (Teffector)/CD4+CD25+ (Treg) ratio. Moreover, a significant increase for CEA and for all 3 markers (standardized values) was found 24–72h after interleukin-2 administration. In patients who survived less than 5years, the Treg cell increase occurred at a significantly shorter time interval than in those who survived longer than 5years (20 vs 45.5months, respectively; P =0.001). These data show laboratory evidence of the effect of immunotherapy as well as that of hormone resistance occuring concomitantly with a laboratory pattern compatible with immune inhibition. [Copyright &y& Elsevier]

We present an 8-year-old girl with evolution of an aneurysmal bone cyst of the proximal fibula after intralesional surgery, treated successfully with one selective transfemoral embolization with N-2-butyl-cyanoacrylate. By the first 5 days, the patient experienced complete pain relief. Post-embolization imaging follow-up showed progressive homogenous trabecular bone formation and gradual reduction of the size of the lesion. These findings canceled our initial consideration for surgical treatment. Three years after the embolization, healing of the lesion and remodeling of the proximal fibula were observed without evidence of recurrence. Our successful results with excellent response seen 3 years after embolization are in favor and should increase the awareness of surgeons regarding embolization for aneurysmal bone cysts in difficult anatomic locations such as the proximal fibula. [ABSTRACT FROM AUTHOR]

The article presents information that the treatment of human immunodeficiency virus infection in patients with the Burkitt lymphoma (HIV-BL) is a difficult challenge which requires multidisciplinary efforts and demanding strategies. It informs that the use of highly active antiretroviral therapy (HAART) has resulted in improved tolerability and efficacy of standard chemotherapy in the HIV-positive patients with diffused large B-cell lymphomas.

The article focuses on the efficacy of continuous corticosteroid therapy and low-dose cytostatic prednisolone and cyclophosphamide to control peripheral T cell lymphomas (PTCL). It mentions that oral combination of prednisolone and cyclophosphamide provides long-term disease control of PTCL as well as long acting immunosuppression for T cell. Moreover, it says that stem cell transplantation (SCT) was recommended to improve prognosis in PTCL.

Many diagnostic and therapeutic advances have been reached for congestive heart failure (HF). However, despite clinical improvement and longer survival conferred by new pharmacological options, this syndrome is associated with high morbidity and mortality. Atrial-synchronized biventricular pacing (cardiac resynchronization therapy, CRT) has proven to be effective treatment in symptomatic patients with reduced left ventricular ejection fraction and electromechanical dyssynchrony. To date, many papers have been published on the role of CRT in improving quality of life, functional and neurohormonal parameters and reducing mortality and hospitalization. Eligible studies were randomized controlled trials of CRT for the treatment of chronic, symptomatic left ventricular dysfunction. Our search began dating back to 1994 and was updated to October 2006. Pooled data from the 6 selected studies showed that CRT reduced all-cause mortality by 28% (hazard ration [HR] = 0.72; 95% confidence interval [CI]: 0.60–0.86) and new hospitalizations for worsening HF by 37% (HR = 0.63; 95% CI: 0.44–0.91). This meta-analysis showed that patients with implantable cardiac defibrillators (ICDs) alone and ICD+CRT had a significant reduction of worsening HF hospitalization rate compared to no CRT-no ICD patients. Among patients with ICDs, CRT showed a slight effect on all-cause mortality reduction but no clear impact on worsening HF rehospitalization. [ABSTRACT FROM AUTHOR]

This article presents information related to high-dose sequential (HDS) chemotherapy for high-risk non-Hodgkin's lymphoma (NHL). High dose chemotherapy with autograft is extensively employed in the management of high-risk lymphoma. This approach is presently first-choice for relapsed high grade NHL and Hodgkin's lymphoma. The original HDS, developed in 1989, includes the sequential delivery of high doses of Cyclophosphamide (CY), Methotrexate and Etoposide given at 15-20 day intervals and finally autograft performed with PBPC collected after CY.

Considerable progress has been made in the treatment of acute myeloid leukemia (AML). However, current therapeutic results are still unsatisfactory in untreated high-risk patients and poorer in those with primary refractory or relapsed disease. In older patients, reluctance by clinicians to treat unfit patients, higher AML cell resistance related to more frequent adverse karyotype and/or precedent myelodysplastic syndrome, and preferential involvement of chemorefractory early hemopoietic precursors in the pathogenesis of the disease further account for poor prognosis, with median survival lower than six months. A general agreement exists concerning the administration of aggressive salvage therapy in young adults followed by allogeneic stem cell transplantation; on the contrary, different therapeutic approaches varying in intensity, from conventional salvage chemotherapy based on intermediate–high-dose cytarabine to best supportive care, are currently considered in the relapsed, older AML patient population. Either patients' characteristics or physicians' attitudes count toward the process of clinical decision making. In addition, several new drugs with clinical activity described as "promising" in uncontrolled single-arm studies failed to improve long-term outcomes when tested in larger randomized clinical trials. Recently, new agents have been approved and are expected to consistently improve the clinical outcome for selected genomic subgroups, and research is in progress in other molecular settings. While relapsed AML remains a tremendous challenge to both patients and clinicians, knowledge of the molecular pathogenesis of the disease is fast in progress, potentially leading to personalized therapy in most patients. [ABSTRACT FROM AUTHOR]