Liam Grogan

Emergence of MRSA in positive blood cultures from patients with febrile neutropenia—a cause for concern

Goals of workFebrile neutropenia (FN) causes considerable morbidity in patients on cytotoxic chemotherapy. Recently, there has been a trend towards fewer Gram-negative and more Gram-positive infections with increasing antibiotic resistance. To assess these patterns, data from a supra-regional cancer centre in Ireland were reviewed.Patients and methodsA 5-year review of all positive blood cultures in patients undergoing anti-cancer chemotherapy was carried out.Main resultsEight hundred and ninety-four patients were reviewed. The mean incidence of FN was 64.2 cases per year. Eight hundred and forty-six blood culture specimens were taken and 173 (20.4%) were culture positive. The isolated organisms were Gram positive (71.1%), Gram negative (27.8%) and fungal (1.1%). Of the Gram-positive organisms, 75.6% were staphylococci. Of these, 67.8% were coagulase-negative staphylococci and 30.1% were Staphylococci aureus. Amongst the S. aureus, 89.3% were methicillin-resistant (MRSA). Vancomycin-resistant enterococci were not identified as a cause of positive blood cultures.ConclusionsAmongst patients with cancer who develop FN in our hospital, Gram-positive bacteria account for the largest proportion. The high proportion of MRSA as a cause of positive blood cultures is of concern.

Increased platelet reactivity in patients with late-stage metastatic cancer

Platelet hyperreactivity is associated with an increased risk of thrombosis. Cancer patients are at an increased risk of thrombosis, a risk that increases with disease progression. While cancer patients show evidence of platelet activation in vivo, few studies have extensively assessed whether these patients display platelet hyperreactivity. We hypothesized that patients with metastatic cancer would display platelet hyperreactivity, reflecting their associated high risk of thrombosis. In a cohort of patients with metastatic cancer (n = 13), we assessed platelet function using well‐established assays of platelet reactivity (agonist‐induced platelet aggregation, spontaneous platelet aggregation, and agonist‐induced P‐selectin expression). In comparison with healthy controls (n = 10), patients with metastatic cancer displayed global platelet hyperreactivity. Agonist‐induced platelet aggregation responses to ADP (adenosine diphosphate), epinephrine, collagen, arachidonic acid, and PAR‐1 (protease‐activated receptor‐1) activating peptide, as well as spontaneous platelet aggregation, were significantly increased in patients with metastatic cancer. Furthermore, agonist‐induced platelet P‐selectin expression was also significantly increased within the patient cohort. We demonstrate that patients with metastatic cancer are characterized by global platelet hyperreactivity, a factor that may contribute to their increased risk of thrombosis.

Small-Cell Lung Cancer Presenting as Diabetes Insipidus and Cushing's Syndrome

Small-cell lung cancer presenting with a combination of cranial diabetes insipidus and Cushings syndrome secondary to ectopic adrenocorticotropin (ACTH) secretion is very rare and has only been described previously in one case report Our patient was a 49 year old man, in whom the initial presenting features of small-cell lung cancer were cranial diabetes insipidus secondary to pituitary metastases and severe hypokalaemia resulting from ectopic ACTH hormone secretion. This case is a remarkable example of the complex metabolic endocrine manifestations of small-cell lung cancer.

20 YEAR OLD LADY WITH A PARASPINAL MASS

A 20 year old female presented with a 4 month history of right upper limb pain and paraesthesias. She had no systemic symptoms and no prior medical or family history of note. MRI revealed a right-sided intradural extramedullary mass extending from C7-T1 and displacing the spinal cord. While awaiting surgery her symptoms progressed to involve the right lower limb. She was re-imaged and the lesion now extended from C5 to T3 with spinal cord compression at C7-T1. The radiological features and recent rapid growth were felt to be in keeping with a large plexiform neurofibroma. The patient underwent emergency resection of the lesion and pathology revealed Hodgkins Lymphoma (HL)-mixed cellularity type. A mediastinal mass was identified on further imaging and biopsy confirmed the diagnosis of HL-stage IV. The patient is currently undergoing treatment with ABVD chemotherapy. CNS-HL is extremely rare and may occur de novo or in association with systemic disease. Lesions may be parenchymal or dural based and are usually intracranial with an increased risk of CNS involvement in HL-mixed-cellularity type as in our patient. This is the first report in the literature of CNS-HL radiologically mimicking a paraspinal plexiform neurofibroma.

Resolution of small cell lung cancer intracranial metastases with standard dose chemotherapy.

SummaryBrain metastases are a well recognized problem in patients with small cell lung cancer (SCLC). Most patients are treated with whole brain cranial irradiation therapy which frequently improves symptoms. In this report we present data on two patients who achieved radiologically confirmed complete resolution of brain metastases treated with standard dose chemotherapy for SCLC.

Bronchoesophageal fistula in a patient with stage IIIB non-small-cell lung cancer.

Journal of Thoracic Oncology • Volume 7, Number 10, October 2012 A 65-year-old male patient with stage IIIB non–small-cell lung cancer (squamous cell carcinoma) treated with palliative chemotherapy (carboplatin area under the curve = 5 Day 1, gemcitabine 1250 mg/m Day 1, Day 8 every 21 days), presented on day 10 after cycle 3 of chemotherapy with progressive worsening, including shortness of breath, cough upon drinking fluids, and fever. His pretreatment staging computed tomography (CT) scan showed bulky subcarinal and mediastinal lymphadenopathy (Fig. 1A, white arrow). Upon presentation with the above symptoms, a computed tomography scan of the thorax showed the presence of a fistula (Fig. 1B, white arrow) between the esophagus (single asterisks) and left main bronchus (double asterisks) with evidence of aspiration pneumonia. Subsequently, a bronchial stent was placed in the left main bronchus (Fig. 1C, white arrows) with improvement of his symptoms. The patient did not receive any further systemic treatment because of worsening performance status. He was discharged to the community palliative care team for further management and died 3 months after his presentation and stent placement.

Acute upper arm ischaemia: a rare presentation of non-Hodgkin's lymphoma

Digital ischaemia has been sparsely reported in current literature. Its association with lymphomatous conditions has been described in even more exceptional occurrences. We present the first case of upper arm ischaemia associated with non-Hodgkin’s lymphoma. A brief literature review of this rare phenomenon is also accompanied with it.

Primary Central Nervous System Lymphoma (PCNSL) occurring in pregnancy

Sirs: A 34 year old female, at 28 weeks gestation, presented with a 7-day history of nausea, vomiting, headaches and left upper limb weakness. Examination revealed significant left hemiparesis involving predominantly the left upper limb. Ocular examinations were normal. T-2 FLAIR sequenced MRI identified homogeneous hyperintense lesions in the right frontal lobe, right medial temporal lobe, basal ganglia and thalamus (Fig. 1). Cerebrospinal fluid assessment including cytology was normal. A clinical diagnosis of post-infectious encephalitis was made. She responded to a combination of intravenous steroids and acyclovir over a period of 2 weeks and was subsequently discharged with tapering steroid dose. She was readmitted 2 weeks later with worsening symptoms. Repeat brain MRI showed the same findings as at initial presentation. As the symptoms recurred with a reducing steroid dose, a possible diagnosis of a lymphoproliferative malignancy was suggested. She then underwent biopsy, from which the specimen showed significant infiltrate of cells with large nuclei in the leptomeningeal and perivascular parenchyma. Immunohistochemistry were positive for CLA and CD20, consistent with high grade B-cell Non-Hodgkins Lymphoma. Systemic involvements were outruled by normal body CT findings and bone marrow examination. Human immunodeficiency virus serology was negative. A diagnosis of Primary Central Nervous System Lymphoma (PCNSL) was made. The patient underwent emergency caesarean section at 31 weeks to a full Apgar score baby girl. A week after delivery, she underwent combination chemoradiotherapy based on the De Angelis regimen, Memorial Sloan Kettering [3]. On completion of chemo-radiotherapy, complete response was documented and she was back in full employment. Fifteen months after treatment, she developed mild impairment of memory, ataxia and depression. Repeat MRI and lumbar puncture showed no evidence of disease recurrence or neurotoxicity. A clinical diagnosis of delayed neurotoxicity associated with combined treatment was made. Otherwise the patient remains well 48 months since diagnosis. Discussion

Frequency, impact and a preclinical study of novel ERBB gene family mutations in HER2-positive breast cancer:

Background: Somatic mutations in the ERBB genes (epidermal growth factor receptor: EGFR, ERBB2, ERBB3, ERBB4) promote oncogenesis and lapatinib resistance in metastatic HER2+ (human epidermal growth factor-like receptor 2) breast cancer in vitro. Our study aimed to determine the frequency of mutations in four genes: EGFR, ERBB2, ERBB3 and ERBB4 and to investigate whether these mutations affect cellular behaviour and therapy response in vitro and outcomes after adjuvant trastuzumab-based therapy in clinical samples. Methods: We performed Agena MassArray analysis of 227 HER2+ breast cancer samples to identify the type and frequency of ERBB family mutations. Of these, two mutations, the somatic mutations ERBB4-V721I and ERBB4-S303F, were stably transfected into HCC1954 (PIK3CA mutant), HCC1569 (PIK3CA wildtype) and BT474 (PIK3CA mutant, ER positive) HER2+ breast cancer cell lines for functional in vitro experiments. Results: A total of 12 somatic, likely deleterious mutations in the kinase and furin-like domains of the ERBB genes (3 EGFR, 1 ERBB2, 3 ERBB3, 5 ERBB4) were identified in 7% of HER2+ breast cancers, with ERBB4 the most frequently mutated gene. The ERBB4-V721I kinase domain mutation significantly increased 3D-colony formation in 3/3 cell lines, whereas ERBB4-S303F did not increase growth rate or 3D colony formation in vitro. ERBB4-V721I sensitized HCC1569 cells (PIK3CA wildtype) to the pan class I PI3K inhibitor copanlisib but increased resistance to the pan-HER family inhibitor afatinib. The combinations of copanlisib with trastuzumab, lapatinib, or afatinib remained synergistic regardless of ERBB4-V721I or ERBB4-S303F mutation status. Conclusions: ERBB gene family mutations, which are present in 7% of our HER2+ breast cancer cohort, may have the potential to alter cellular behaviour and the efficacy of HER- and PI3K-inhibition.

Abstract A059: Lifestyle and health-related quality of life in men with metastatic prostate cancer

Background: Patients with metastatic prostate cancer live with a considerable disease burden that may have a profound impact on physical activity and quality of life. This patient group may survive for many years after disease onset; however, there is little evidence on their habitual levels of physical activity. The aim of this study was to investigate physical activity levels and associated health-related quality of life in prostate cancer patients with bone metastases. Methods: ExPeCT (Exercise, Prostate Cancer and Circulating Tumour Cells: CTRIAL-IE 15-21) (ClincalTrials.gov identifier NCT02453139) is an ongoing multicenter trial examining the effect of a 6-month structured exercise intervention for patients with metastatic prostate cancer. Participants complete questionnaires examining self-reported health-related quality of life (FACT-P), sleep (Pittsburgh Sleep Index), depression (PHQ-9), and physical activity (Harvard Health Professionals Study Questionnaire) at baseline, three, and six months. Analysis of 3- and 6-month data is ongoing. Result: An interim analysis of the baseline outcome measures of 64 patients with bone metastases was completed (mean age 69.4 (SD 7.35) years and mean BMI 29.2 (SD 5.8) kg/m2). Median time since diagnosis was 34 months (IQR 7-54) and 55% (n=35) of participants had >1 region affected by metastatic disease. Preliminary data demonstrated that 38% (n=24) of participants did not meet the current aerobic exercise guidelines for cancer survivors. In total, 20% (n=13) of participants reported engaging in vigorous activity and 16% (n=11) reported completing resistance exercise. There was no correlation found between physical activity levels and quality of life (r=0.01), sleep (r=0.02), or depression (r=-0.15) scores. The majority of participants (61% (n=41)) had sleep scores of >7, indicative of poor sleep quality. Sleep scores correlated negatively with global quality of life (r =-0.55, p Discussion: Findings highlight the association between reduced quality of life and poor sleep quality among men with metastatic prostate cancer. In addition, data suggest a high prevalence of suboptimal physical activity levels in this population. Patients with metastatic disease may benefit from lifestyle interventions that aim to increase physical activity levels. Citation Format: Grainne Sheill, Lauren Brady, Emer Guinan, Juliette Hussey, David Hevey, Tatjana Vlajnic, Orla Casey, Anne-Marie Baird, Fidelma Cahill, Mieke Van Hemelrijck, Nicola Peat, Sarah Rudman, Thomas Lynch, Rustom P. Manecksha, Brian Hayes, Moya Cunningham, Liam Grogan, John McCaffrey, Dearbhaile M. O’Donnell, Ray McDermott, John O Leary, Stephen P. Finn. Lifestyle and health-related quality of life in men with metastatic prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr A059.