Centre for Immunobiology

Background: Direct-acting anti-viral therapy (DAA) has transformed hepatitis C virus (HCV) care, particularly in patients with decompensated cirrhosis. However, their impact on hepatocellular carcinoma (HCC) remains unclear. Aim: To use a national registry of patients with advanced liver disease to explore the relationship between DAA therapy and HCC. Methods: All patients with de novo HCC post DAA therapy were frequency matched with patients who did not develop HCC. Demographic, clinical and laboratory data were obtained. Cross-sectional imaging and multidisciplinary team reports were reviewed for dates of HCC diagnosis and HCC progression. Patients were categorised by treatment outcome and time of HCC development. Data were examined by multivariable analysis and Kaplan-Meier estimation. Results: Eighty patients with HCC were compared with 165 patients without HCC, treated between June 2014 and September 2015. Mean follow-up from start of DAA therapy was 32.4 months. Twenty-eight patients were diagnosed with early HCC (within 6 months of therapy) and 52 presented late. Baseline nonmalignant lesions (HR: 1.99), thrombocytopaenia (HR: 1.59) and diabetes (HR: 1.68) increased likelihood of HCC. Response to therapy was reduced in patients who developed liver cancer (SVR in patients with HCC = 54/80 (68%), SVR in patients without HCC = 143/165 (87%), P < 0.001, OR: 3.13, 95% CI: 1.64-5.99). We found no difference between tumour size, progression or survival between viraemic and nonviraemic patients. Conclusion: There is no alteration in prognosis or cancer progression following HCC development after HCV treatment. However, baseline nonmalignant liver lesions, diabetes and thrombocytopaenia increase the risk of HCC, and HCC is associated with a decreased SVR rate. | 205 MECCI Et al.

ObjectiveLiver biopsy is the most accurate method for determining stage and grade of injury in non-alcoholic fatty liver disease (NAFLD). Given risks and limitations of biopsy, non-invasive tests such as NAFLD fibrosis score, aspartate transaminase (AST) to platelet ratio index, Fib-4, AST/alanine transaminase ratio and BARD are used. Prevalence and severity of NAFLD and metabolic syndrome vary by ethnicity, yet tests have been developed in largely white populations. We tested our hypothesis that non-invasive tests that include metabolic parameters are less accurate in South Asian compared with white patients.DesignRetrospective cross-sectional.SettingSpecialist liver centre.PatientsPatients with histologically confirmed NAFLD.InterventionsScores calculated using clinical data taken within 1 week and compared with histology (Kleiner).Main outcome measuresDiagnostic test characteristics.Results175 patients were identified. South Asians (n=90) were younger, had lower body mass index a...

Nuclear medicine is a powerful diagnostic technique able to detect inflammatory foci in human disease. A wide range of agents have been evaluated for their ability to distinguish lesions due to microbial infection from those due to sterile inflammation. Advances continue to be made on the use of radiolabelled antibiotics which as well as being highly specific in the diagnosis of infection may be useful in monitoring the treatment and course of disease. Here we provide an update on in-vitro and clinical studies with a number of established and novel radiopharmaceuticals

We read the article by Donohoe et al. with great interest and appreciation that the Society would attempt some standardization for brain death in the Journal of Nuclear Medicine (1). There is, however, some valuable information that should accompany this procedure guideline. It is vital for interpreting physicians to understand that the results must completely meet the strict criteria for whole-brain death. This is important for the protection of both the patient and the physician. To meet the criteria for whole-brain death, perfusion must be absent from the whole brain, both cerebrum and cerebellum (2). Without the use of persistent agents, accurate evaluation of brain perfusion is not possible (2). Spieth et al. state, "Unlike DTPA (technetium 99m-diethylene-triaminepentaacetic), HMPAO (technetium 99m-hexamethylpropylene amine oxime) normally visualizes the gray matter of the cerebellum, midbrain, and medulla. These areas must be evaluated to meet the strict criteria for brain death." (3). These findings suggest that persistent agents are a better choice for cerebral perfusion studies to determine brain death (3). Spieth et al. explain, "Although HMPAO is more expensive than DTPA, it is less expensive than the total cost of a repeat study using DTPA. A single HMPAO dosage can be reimaged should there be equipment or other technical failures during acquisition." (3). At that time, HMPAO was the only available technetium-labeled agent able to meet the strict criteria for the clinical confirmation of whole-brain death (3). Neurolite (Bristol-Myers Squibb Medical Imaging, Inc.) is another persistent agent available since the above articles were written.

This study compared the possibilities and limitations of 99mTc-labeled synthetic peptides derived from two human antimicrobial peptides, namely, ubiquicidin (UBI) and lactoferrin (hLF), for the scintigraphic detection of bacterial and fungal infections in mice and rabbits. The rationale of our approach was that selected peptides accumulate in infected areas but not in sterile inflammatory lesions, because they bind preferentially to microorganisms. 99mTc-labeled human neutrophil peptides (defensins), ciprofloxacin, and human polyclonal IgG were included as control agents. 99mTc-labeled peptides and control agents were injected intravenously into animals that had been injected intramuscularly 18 h earlier with multidrug-resistant Staphylococcus aureus, Klebsiella pneumoniae, or fluconazole-resistant Candida albicans. Sterile inflammatory sites were induced by the injection of heat-killed microorganisms or lipopolysaccharide (LPS) into the thigh muscle. Up to 4 h after injection, the ...

tumours reported in association with cervical embryonal rhabdomyosarcoma have been of intermediate differentiation. The presence of collections of cells with bizarre nuclei within the Sertoli-Leydig cell tumour was unusual and initially resulted in consideration of metastatic rhabdomyosarcoma involving the ovarian neoplasm. However, we consider these to represent collections of bizarre nuclei which are occasionally found in otherwise typical ovarian sex cord-stromal neoplasms, including granulosa and Sertoli-Leydig cell tumours. 15 Morphologically these resemble the bizarre cells sometimes found in uterine leiomyomas and are probably degenerative in nature. Focal positivity of the bizarre cells with a inhibin suggested that they were of sex cord derivation. Desmin staining was performed on the ovarian tumour when the possibility of metastatic rhabdomyosarcoma was considered. The Sertoli and Leydig cell components and the bizarre cells were focally positive, and we make the point that ovarian sex cord-stromal tumours may stain with muscle markers, including desmin. 16 Indeed one of us (WGM) has observed that desmin is not uncommonly expressed in ovarian sex cordstromal tumours. We also mention the fact that collections of bizarre cells are rarely found in otherwise typical cervical embryonal rhabdomyosarcoma. 17 18 In summary, we report a case in which a cervical embryonal rhabdomyosarcoma and an ovarian Sertoli-Leydig cell tumour of intermediate differentiation coexisted in a 13-year-old girl, the fourth documented example of this association. Given that these are two relatively uncommon neoplasms, we feel that the association is more than coincidental. The basis of the association is not known, but a genetic link seems likely.

Aims-To evaluate the pharmacokinetics of once daily (OD) gentamicin and its eVectiveness as part of an OD regimen for the empirical treatment of febrile neutropenia in children with cancer. Subjects-59 children aged 6 months to 16 years (mean (SD) 5.7 (4) years) with febrile neutropenia (neutrophil count < 0.5 × 10 9 /l) after chemotherapy. Methods-Over one year, 113 febrile neutropenic episodes were treated empirically with an OD antibiotic regimen of ceftriaxone (80 mg/kg; maximum 4 g) and gentamicin (7 mg/kg; infused over 60 minutes, no maximum). The patients were assessed after 48 hours. Results-86 of the 113 episodes settled with the first line antibiotic regimen. In 29 episodes, blood cultures identified a causative bacterial pathogen; for 17 of these, the first line antibiotic regimen was adequate; in four episodes, although the episode settled, ceftriaxone was replaced by a more appropriate antibiotic and OD gentamicin was continued; in the remaining eight episodes, a glycopeptide antibiotic was deemed necessary. There was no failure of treatment in organisms sensitive to gentamicin, including Pseudomonas aeruginosa. In 27 episodes (24%), resolution was obtained by the empirical introduction of a second line regimen of ceftazidime and a glycopeptide antibiotic, and/or amphotericin. Gentamicin concentrations were measured in 110 episodes and they were all below the 24 hour line indicating that there was no need to change the dosing interval. In two episodes (2%), serum creatinine rose transiently by more than 50% of the baseline concentration. Although there was no vestibular toxicity, three of 30 children who underwent pure tone audiometry reported high frequency hearing loss in one ear. Conclusion-OD gentamicin can be used safely and eVectively to treat febrile neutropenia in children with cancer. When used for a short period (< 5 days), in children not receiving other nephrotoxic drugs and who have normal serum creatinine, serum gentamicin estimations are unnecessary.