Use of FDG PET/CT in identification of bone marrow involvement in diffuse large B cell lymphoma and follicular lymphoma: comparison with iliac crest bone marrow biopsy.

Background Non-Hodgkin's lymphoma (NHL) accounts for around 4% of new cancer cases annually. Bone marrow involvement is important for staging and management. Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is used increasingly to identify this, in addition to bone marrow biopsy (BMB), which is seen as "gold" reference standard. Purpose To compare determination of bone marrow involvement by FDG PET/CT against BMB in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Material and Methods This was a retrospective study of patients with histologically confirmed NHL at a single UK cancer center undergoing pre-treatment FDG PET/CT and BMB between June 2010 and February 2013. Information was collected from patient notes, cancer registry, histological and imaging reports. Diagnostic accuracy of FDG PET/CT was determined, compared to BMB as the reference standard. Results Twenty-four patients with DLBCL and 12 with FL were included. Five DLBCL patients had bone marrow involvement on PET/CT; all were confirmed on BMB. Three FL patients had marrow involvement on PET/CT but not on BMB; one FL patient had positive BMB but negative PET/CT. Using BMB as the reference standard, the sensitivity and specificity of FDG PET/CT for detecting bone marrow involvement in DLBCL were 100% and 100%, respectively, and in FL were 0% and 72.7%, respectively. Conclusion FDG PET/CT is accurate for detection of bone marrow involvement in newly diagnosed DLBCL, but not FL. In DLBCL, positive FDG PET/CT may negate the need for routine BMB, although BMB in addition or combination may be appropriate if this would influence management or prognosis.

Gene Therapy for Pyoderma Gangrenosum: Optimal Transfection Conditions and Effect of Drugs on Gene Delivery in the HaCaT Cell Line Using Cationic Liposomes.

BACKGROUND/AIMS: Pyoderma gangrenosum (PG) is a rare ulcerative skin disease, currently treated empirically with immunosuppression. PG is a good target for gene therapy since the skin is easily accessible. This study used the FDA-approved vector Lipofectamine® 2000 to investigate in vitro transfection of skin keratinocytes. The aim was to determine an optimum transfection protocol, including the effect of drugs currently used to treat PG on the efficiency of gene transfer, since gene therapy is unlikely to be used as monotherapy. METHODS: Cells of the HaCaT line were transfected with the lacZ reporter gene, and transgene expression was measured after a given time period. Conditions tested were: relative concentrations of DNA and Lipofectamine®, time from transfection to measurement of expression, pH, and exposure to clinically relevant drugs (hydrocortisone, methotrexate, infliximab). RESULTS: The greatest levels of ß-galactosidase expression were observed using a DNA:Lipofectamine® ratio of 1:5 (µg/µl) on day 3 after transfection, using culture medium at pH 7, and in the presence of hydrocortisone. Transfection efficiency was reduced by the presence of methotrexate and not significantly affected by infliximab. CONCLUSION: Gene therapy is a potential future strategy for the management of PG; this study is a step towards the development of a topical gene-based agent.

Modulation of TCR Signaling by Tyrosine Phosphatases: From Autoimmunity to Immunotherapy.

Early TCR signaling is dependent on rapid phosphorylation and dephosphorylation of multiple signaling and adaptor proteins, leading to T cell activation. This process is tightly regulated by an intricate web of interactions between kinases and phosphatases. A number of tyrosine phosphatases have been shown to modulate T cell responses and thus alter T cell fate by negatively regulating early TCR signaling. Mutations in some of these enzymes are associated with enhanced predisposition to autoimmunity in humans, and mouse models deficient in orthologous genes often show T cell hyper-activation. Therefore, phosphatases are emerging as potential targets in situations where it is desirable to enhance T cell responses, such as immune responses to tumors. In this review, we summarize the current knowledge about tyrosine phosphatases that regulate early TCR signaling and discuss their involvement in autoimmunity and their potential as targets for tumor immunotherapy.

Preparing medical students for clinical practice: easing the transition.

The transition from medical student to junior doctor is a challenge; the UK General Medical Council has issued guidance emphasizing the importance of adequate preparation of medical students for clinical practice. This study aimed to determine whether a junior doctor-led simulation-based course is an effective way of preparing final year medical students for practice as a junior doctor.We piloted a new 'preparation for practice' course for final year medical students prior to beginning as Foundation Year 1 (first year of practice) doctors. The course ran over three days and consisted of four simulated stations: ward round, prescribing, handover, and lessons learnt. Quantitative and qualitative feedback was obtained.A total of 120 students attended (40 on each day) and feedback was collected from 95 of them. Using a scale of 1 (lowest) to 5 (highest), feedback was positive, with 99% and 96% rating 4 or 5 for the overall quality of the program and the relevance of the program content, respectively. A score of 5 was awarded by 67% of students for the ward round station; 58% for the handover station; 71% for the prescribing station, and 35% for the lessons learnt station. Following the prescribing station, students reported increased confidence in their prescribing.Preparation for practice courses and simulation are an effective and enjoyable way of easing the transition from medical student to junior doctor. Together with 'on-the-job' shadowing time, such programs can be used to improve students' confidence, competence, and ultimately patient safety and quality of care.

Negative 18F-FDG-PET-CT may exclude residual or recurrent disease in anal cancer.

OBJECTIVES: The incidence of anal cancer is increasing in Western countries. Fluorine-18 fluorodeoxyglucose (F-FDG) PET-computed tomography (CT) is used in the assessment of anal cancer, but its routine use is not established. The aim of this study was to assess the value of F-FDG-PET-CT in staging and post-treatment assessment in anal cancer and to determine its impact on management. METHODS: This was a retrospective analysis of patients with anal cancer treated at the Sussex Cancer Centre who underwent PET-CT between November 2004 and September 2014. Information was retrieved from patient notes and the local cancer register, and verified by referring consultants in all cases. RESULTS: A total of 75 PET-CT scans in 52 patients were identified, representing 38.5% of patients diagnosed with anal cancer during this period. There were 24 staging scans and 51 post-treatment scans. Management was altered following 45.8% of staging scans and 56.0% of all scans, mostly changing treatment type or radiotherapy volume. Out of 28 positive post-treatment scans, 71.4% were true positives, 7.1% were false positives and 21.4% showed nonspecific uptake. Of the 23 negative post-treatment scans, all remained disease free at clinical/radiological follow-up (median follow-up 25 months). The sensitivity and specificity of post-treatment PET-CT were 100 and 74%, respectively. Negative predictive and positive predictive values were 100 and 71%, respectively. CONCLUSION: Evidence is evolving for the use of PET-CT in anal cancer. Because of a high negative predictive value, our series shows that PET-CT can be used in the assessment of treatment response to exclude residual/recurrent disease.