Results From a Large,Multicenter, Retrospective Analysis On Radium223 Use in Metastatic Castration-resistant Prostate Cancer (mCRPC) in the Triveneto Italian Region

Background

Radium 223 was introduced for metastatic castration-resistant prostate cancer based on the results of a randomized controlled trial showing risk reduction for death and skeletal events. Our aim was to evaluate the outcome of patients receiving radium 223 in a real-world setting.

Intracranial tumors of the first year of life

The introduction of new diagnostic tools for neuroimaging has resulted in the early recognition of congenital brain tumors. In the present report we describe a personal series of 39 children and an International Multicenter Series of 876 children with brain tumors, in whom the diagnosis was obtained during the first 12 months of life. Most of the tumors were located within the supratentorial compartment. In spite of a relatively high operative mortality, surgery still appears to be the more effective therapy. Radiotherapy in this age group is of a scarce value, due to the vulnerability of the infantile brain. At the present time, chemotherapy still plays a controversial role.     

Hemolytic anemia during pegylated IFN-alpha2b plus ribavirin treatment for chronic hepatitis C: ribavirin is not always the culprit.

A 53-year-old woman admitted to our department for histologically proven chronic hepatitis C had previously been treated with pegylated interferon-alpha2b (PEG-IFN) plus ribavirin. Combination therapy had been withdrawn after 5 weeks because of severe anemia (hemoglobin 8.2 g/dl) despite a reduction in ribavirin dose. A second liver biopsy showed moderate chronic hepatitis with portoportal and portocentral bridges (Ishak score: grading 14/18, staging 4-5/6). Consequently, the patient was retreated with 1.5 microg/kg body weight weekly PEG-IFN and 1000 mg/day ribavirin. Ribavirin was withdrawn about 3 months later because of anemia. After 1 month of PEG-IFN alone, hemoglobin had decreased further to reach 7.9 g/dl; consequently IFN was stopped. An elevated reticulocyte count, indirect bilirubin concentration, and lactic dehydrogenase (LDH) concentration, and a positive direct Coombs test (IgG3, C3d also for panagglutinant irregular antibodies on eluate) led us to diagnose autoimmune hemolytic anemia (AHA). The patient received 1 mg/kg body weight/day prednisone, and all parameters normalized within 20 days. This is the first case of IFN-related AHA during PEG-IFN plus ribavirin therapy. Physicians should be aware that PEG-IFN can be the cause of AHA during a ribavirin-containing regimen for chronic hepatitis C.     

Uniportal vs standard three-port VATS technique for spontaneous pneumothorax: comparison of post-operative pain and residual paraesthesia.

OBJECTIVE: VATS using the conventional three ports is currently the technique of choice for blebectomy/bullectomy for spontaneous pneumothorax. However, the procedure has recently been shown to have neurological complications related to the port sites. Uniportal VATS has recently been proposed as an alternative to conventional three-port VATS. It is anticipated that the single incision will predispose to a lower incidence of neurological complications. METHODS: We report our initial single surgeon experience of uniportal VATS (n = 16) and provide a comparison of post-operative pain and residual paraesthesia to conventional three-port procedures (n = 19) for the same pathology. RESULTS: In both groups, the pneumothorax pathology was principally primary. There was no difference between the groups in terms of age, spirometry, tissue resected, drainage time and inpatient stay. A difference was, however, noted in inpatient pain scores. The uniportal group had a lower median score of 0.4 (visual analogue range 0-4) while the three-port technique reported 0.8 (P = 0.06, Mann-Whitney test). The maximum score trend was similar (1.4 vs. 2.6, respectively, P < 0.001, Mann-Whitney test). Follow-up for uniportal and three-port VATS averaged 9.4+/-6.6 and 32.1+/-9.9 months, respectively. One patient in the three-port group had a pneumothorax recurrence. Three-port VATS also had a higher residual pain score (0.5) compared to uniportal VATS (0.3). Of clinical significance was the incidence of neurological complications. Eighty-six percent of uniportal patients reported no symptoms. The remaining experienced only mild 'numbness' or 'swelling'. However, in the three-port group, only 42% reported no symptoms. A similar number experienced 'numbness'. Two females described sexual dysfunction due to altered breast sensitivity. Seventeen percent (2/12) reported 'pins and needles'. CONCLUSIONS: Uniportal VATS appears to be tolerable, safe and efficient in treating spontaneous pneumothorax in our series. Moreover, post-operative pain and paraesthesia incidence was lower than three-port VATS. Prospective randomised trials are important to evaluate this technique.     

Lyme disease: ocular manifestations

We present three cases of Lyme disease, complicated by ocular manifestations. These included optic nerve abnormalities and corneal opacities.     

Elective transplant pneumonectomy in a 38-year-old man.

Transplant pneumonectomy is a rarely performed procedure. It is occasionally carried out in the course of retransplantation. To our knowledge, resection of a transplanted lung without its replacement and with successful outcome in the adult has not been previously reported. We present a case of elective left transplant pneumonectomy in a 38-year-old man 6 years after left single-lung transplant. At 12 months after resection, the patient remains well, with good exercise tolerance.     

Differential gene expression in cultured osteoblasts and bone marrow stromal cells from patients with Paget's disease of bone.

Paget's disease is a focal condition of bone. To study changes in cells within pagetic lesions, we cultured osteoblasts and stromal cells from 22 patients and compared gene expression in these cells to cells from healthy bone. We identified several differentially regulated genes, and we suggest that these changes could lead to the formation of the lesions. INTRODUCTION: Paget's disease is a focal condition of bone of unknown cause. Although it is regarded as primarily an osteoclast disorder, the tight coupling of the activity of osteoclasts and osteoblasts suggests that the osteoblast could play a key role in its pathogenesis. The aim of the study was to identify possible changes in pagetic osteoblasts and stromal cells that might contribute to the development of pagetic lesions. MATERIALS AND METHODS: Candidate genes were identified based on known bone cell regulators, supplemented with microarray analysis. Gene expression was determined by real-time PCR in primary cultures of osteoblasts and bone marrow stromal cells from pagetic patients and control subjects. Concentrations of secreted proteins were determined by ELISA. RESULTS: Dickkopf1 mRNA and protein levels were increased in both pagetic osteoblast and stromal cell cultures, and interleukin (IL)-1 and IL-6 were overexpressed in pagetic osteoblasts. These changes parallel recent findings in myeloma bone disease, which shares some clinical similarities with Paget's disease. Alkaline phosphatase was overexpressed, and bone sialoprotein and osteocalcin were underexpressed in pagetic osteoblasts, consistent with their circulating levels in pagetic patients. It is hypothesized that overexpression of Dickkopf1, IL-1, and IL-6 would result in stimulation of osteoclast proliferation and inhibition of osteoblast growth, leading to the development of the characteristic lytic bone lesions. By stimulating osteoblast differentiation, Dickkopf1 and IL-6 may also promote mineralization, leading to the conversion of lytic lesions to sclerotic. CONCLUSIONS: These findings suggest that dysregulated gene expression in pagetic osteoblasts could cause the changes in bone cell number and function characteristic of Paget's disease.