Simultaneous 99mTc double labelling of the hepatic reticuloendothelial system and of the red blood cells: a simplified method for the detection of liver hemangiomas

Sonographic images of liver hemangioma are not specific. Causal detection imposes further investigations (angiography, CT, NMR) which are not always practicable. 99mTc-red blood cells study after 99mTc colloid liver scintigraphy has been already proposed. Ten patients with hepatic hemangiomas were evaluated by simplified, simultaneous in vivo double labelling of the reticuloendothelial system and red blood cells by means of successive i.v. injections of SnCl2, 99mTc colloid albumin and 99mTc-pertechnetate. Focal colloid defects filled with the labelled RBC were revealed in 9/10 liver hemangiomas. Angioscintigraphy showed decreased perfusion and RBC scintigraphy an increased blood volume in the focal colloid defects due to the hemangiomas.     

Unusual clinical presentation of Mycobacterium fortuitum infection in an immunocompetent woman

The Mycobacterium fortuitum group of rapidly growing nontuberculous mycobacteria is an uncommon cause of renal infection, particularly in otherwise healthy hosts. We describe a case of nephritis due to M. fortuitum in an immunocompetent woman with a clinical and radiological diagnosis of renal tuberculosis.     

Long-Term Pooled Safety Analysis of Palbociclib in Combination with Endocrine Therapy for Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Updated Analysis with up to 5 Years of Follow-Up

BackgroundPrevious studies demonstrated the tolerability of palbociclib plus endocrine therapy (ET). This analysis evaluated safety based on more recent cutoff dates and a longer palbociclib treatment exposure.Patients and MethodsData were pooled from three randomized studies of patients with hormone receptor‐positive/human epidermal growth factor receptor 2‐negative (HR+/HER2−) advanced breast cancer (ABC), including postmenopausal women who had not received prior systemic treatment for advanced disease (PALOMA‐1/‐2) and pre‐ and postmenopausal women who had progressed on prior ET (PALOMA‐3).ResultsUpdated cutoff dates were December 21, 2017 (PALOMA‐1), May 31, 2017 (PALOMA‐2), and April 13, 2018 (PALOMA‐3). Total person‐years of treatment exposure were 1,421.6 with palbociclib plus ET (n = 872) and 528.4 with ET (n = 471). Any‐grade neutropenia and infections were more frequent with palbociclib plus ET (82.1% and 59.2%, respectively) than with ET (5.1% and 39.5%). The hazard ratios were 1.6 (p = .0995) for grade 3/4 infections, 1.8 (p = .4358) for grade 3/4 viral infections, 1.4 (p = .0001) for infections, and 30.8 (p < .0001) for neutropenia. Febrile neutropenia was reported in 1.4% of patients receiving palbociclib plus ET. Cumulative incidence of all‐grade hematologic adverse events in both arms peaked during the first year of treatment and plateaued over the 5 subsequent years. Interstitial lung disease was reported in 13 patients receiving palbociclib plus ET and 3 receiving ET.ConclusionThis 5‐year, long‐term analysis demonstrated that palbociclib plus ET has a consistent and stable safety profile and is a safe treatment for patients with HR+/HER2− ABC.Implications for PracticeSeveral treatments for patients with breast cancer are associated with long‐term or latent adverse events. This long‐term, 5‐year analysis demonstrated that palbociclib plus endocrine therapy has a consistent and stable safety profile without cumulative or delayed toxicities. These results further support palbociclib plus endocrine therapy as a safe and manageable treatment in clinical practice for patients with hormone receptor‐positive/human epidermal growth factor receptor 2‐negative advanced breast cancer.     

Uncovering the genomic heterogeneity of multifocal breast cancer

Multifocal breast cancer (MFBC), defined as multiple synchronous unilateral lesions of invasive breast cancer, is relatively frequent and has been associated with more aggressive features than unifocal cancer. Here, we aimed to investigate the genomic heterogeneity between MFBC lesions sharing similar histopathological parameters. Characterization of different lesions from 36 patients with ductal MFBC involved the identification of non‐silent coding mutations in 360 protein‐coding genes (171 tumour and 36 matched normal samples). We selected only patients with lesions presenting the same grade, ER, and HER2 status. Mutations were classified as ‘oncogenic’ in the case of recurrent substitutions reported in COSMIC or truncating mutations affecting tumour suppressor genes. All mutations identified in a given patient were further interrogated in all samples from that patient through deep resequencing using an orthogonal platform. Whole‐genome rearrangement screen was further conducted in 8/36 patients. Twenty‐four patients (67%) had substitutions/indels shared by all their lesions, of which 11 carried the same mutations in all lesions, and 13 had lesions with both common and private mutations. Three‐quarters of those 24 patients shared oncogenic variants. The remaining 12 patients (33%) did not share any substitution/indels, with inter‐lesion heterogeneity observed for oncogenic mutation(s) in genes such as PIK3CA, TP53, GATA3, and PTEN. Genomically heterogeneous lesions tended to be further apart in the mammary gland than homogeneous lesions. Genome‐wide analyses of a limited number of patients identified a common somatic background in all studied MFBCs, including those with no mutation in common between the lesions. To conclude, as the number of molecular targeted therapies increases and trials driven by genomic screening are ongoing, our findings highlight the presence of genomic inter‐lesion heterogeneity in one‐third, despite similar pathological features. This implies that deeper molecular characterization of all MFBC lesions is warranted for the adequate management of those cancers. © 2015 The Authors. Pathological Society of Great Britain and Ireland.     

Immunomodulation via Chemotherapy and Targeted Therapy: A New Paradigm in Breast Cancer Therapy?

Cytotoxic chemotherapy in the treatment of tumors has traditionally been thought to be immunosuppressive. Increasing evidence suggests the contrary and has introduced the concept of ‘immunogenic’ chemotherapy or, in other words, the concept that the innate and adaptive immune systems are critical in determining the long-term efficacy of some cytotoxic-based (and radiotherapy-based) regimens. The underlying mechanisms how these therapies can stimulate an antitumor immune response have been demonstrated recently. In this article, we review the background of this new paradigm and how combinations of traditional agents with the new immunotherapeutic therapies may significantly advance our treatment of breast cancer.     

Castleman's disease and HIV infection in Australia

OBJECTIVES: To describe, retrospectively, the Australian experience of multi-centric Castleman's disease (MCD) in the setting of HIV infection, specifically with the advent of HAART, and newer chemotherapeutic agents. PATIENTS AND METHODS: HIV-infected patients diagnosed with MCD since 1994, were identified from three major HIV treatment centres in Australia. Demographic and disease characteristic variables were collated by the National Centre in HIV Epidemiology and Clinical Research. RESULTS: Eleven patients were identified with MCD. Medial follow up was 46 (18-57) months. All had CD4 cell counts less than 500 cells/microL. All but one patient was receiving HAART at the time of diagnosis. Nine of the 11 patients had Kaposi's sarcoma (KS) and two patients also developed non-Hodgkin's Lymphoma (NHL). All patients received chemotherapy for MCD. The response rate from Chemotherapy was 64%. Only two patients achieved sustained remissions. The median survival was 21.9 (1-52) months. The mortality was 45% from MCD and its related complications. CONCLUSION: MCD in HIV infected patients is a rare and life-threatening disorder. There is limited recent information on optimal treatment for MCD. MCD in our series appeared to be a chemo-responsive disease. In our experience, treatment with liposomal anthracycline was associated with good response rates and acceptable toxicity in several patients, and therefore merits further exploration to establish its role. Treatment in the future may concentrate on novel agents such as anti-interleukin 6, anti-CD20 antibodies, thalidomide and viral ablation.