18F-FDG PET/CT focal, but not osteolytic, lesions predict the progression of smoldering myeloma to active disease.

Identification of patient sub-groups with smoldering multiple myeloma (SMM) at high risk of progression to active disease (MM) is an important goal. 18F-FDG PET/CT (positron emission tomography (PET) integrated with computed tomography (PET/CT) using glucose labelled with the positron-emitting radionuclide (18)F) allows for assessing early skeletal involvement. Identification of osteolytic lesions by this technique has recently been incorporated into the updated International Myeloma Working Group criteria for MM diagnosis. However, no data are available regarding the impact of focal lesions (FLs) without underlying osteolysis on time to progression (TTP) to MM. We hence prospectively studied a cohort of 120 SMM patients with PET/CT. PET/CT was positive in 16% of patients (1 FL: 8, 2 FLs: 3, >3 FLs: 6, diffuse bone marrow involvement: 2). With a median follow-up of 2.2 years, 38% of patients progressed to MM, in a median time of 4 years, including 21% with skeletal involvement. The risk of progression of those with positive PET/CT was 3.00 (95% confidence interval 1.58-5.69, P=0.001), with a median TTP of 1.1 versus 4.5 years for PET/CT-negative patients. The probability of progression within 2 years was 58% for positive versus 33% for negative patients. In conclusion, PET/CT positivity significantly increased the risk of progression of SMM to MM. PET/CT could become a new tool to define high-risk SMM.

Using PET-CT in the restaging of primitive mediastinal B-cell lymphoma (PMBCL) after chemotherapy: which criteria should we use?

AIM: Primitive mediastinal B-cell lymphoma (PMBCL) is a relatively rare form of non-Hodgkin lymphoma (NHL), typically concerning the youngster, with an aggressive course and poor prognosis. The therapy generally consists of high dose chemotherapy followed by radiotherapy. PET-CT is used at staging, restaging after chemotherapy and after radiotherapy, or when relapse is suspected. Aim of the study was to compare different criteria in the evaluation of response to chemotherapy in this setting. METHODS: Thirty-eight patients with PMBCL (15 M, 23 F, median age 33 yrs [range 18-79]), all treated with chemo-immunotherapy and radiotherapy, who had undergone baseline (b-PET) and end of chemotherapy (f-CHT-PET) 18F-FDG-PET-CT scans at our institution between July 2004 and September 2014 were retrospectively re-evaluated; the median follow-up was 42 months (range 4-109), at which 4/38 (11%) had died, 5/38 (13%) were in partial response (PR) and 29/38 (76%) were in complete response (CR). The primary endpoint was progression-free survival (PFS), while the secondary one was overall survival (OS), according to the Cheson criteria. SUV max of the mediastinal disease mass at staging, of the residual mass at CT after chemo-immunotherapy, SUV max of the liver and of the mediastinal blood pool (MBP) were calculated for all patients. RESULTS: In our population, we observed that: 1) visual criteria performs better when positivity-negativity threshold is set at point 3 of the 5-point scale (5-PS); 2) semiquantitative approach by use of Δ SUV max performs better when the threshold is set at 66% decrease: in fact, at Δ SUV max analysis with 66% decrease, 9 patients resulted positive at the test (Δ SUV max ≤66%), 29 negative (Δ SUV max >66%). CONCLUSION: In our population Δ SUV max could be working well in these patients because the baseline values are very high and very homogeneous. Our data, though limited in numerosity of patients and events, suggests that in this particular setting the use of the 5-PS reporting system could not be the best tool available; on the other hand, Δ SUV max could prove to be reliable in the evaluation of response to chemotherapy.

Involvement of immune response in the pathogenesis of amyotrophic lateral sclerosis: a therapeutic opportunity?

The immune system has been found to be involved with positive and negative effects in the nervous system of amyotrophic lateral sclerosis (ALS) patients. In general, T cells, B cells, NK cells, mast cells, macrophages, dendritic cells, microglia, antibodies, complement and cytokines participate in limiting damage. Several mechanisms of action, such as production of neurotrophic growth factors and interaction with neurons and glial cells, have been shown to preserve these latter from injury and stimulate growth and repair. The immune system also participates in proliferation of neural progenitor stem cells and their migration to sites of injury and this activity has been documented in various neurologic disorders including traumatic injury, ischemic and hemorrhagic stroke, multiple sclerosis, infection, and neurodegenerative diseases (Alzheimer's disease, Parkinson's disease and ALS). Many therapies have been shown to stimulate the protective and regenerative aspects of the immune system in humans, such as intravenous immunoglobulins, and other experimental interventions such as vaccination, minocycline, antibodies and neural stem cells, have shown promise in animal models of ALS. Consequently, several immunosuppressive and immunomodulatory therapies have been tried in ALS, generally with no success, in particular intravenous immunoglobulins. The multiple aspects of the immune response in ALS are beginning to be appreciated, and their potential as pharmacologic targets in neurologic disease is being explored.

Diagnosis of bladder cancer at 465 MHz.

Current methods for bladder cancer investigation involve cystoscopy, ultrasound scanning, and contrast urography, with additional information provided by cytology. These methods, although having a high detection rate, are expensive, time-consuming, invasive, and uncomfortable. Therefore, there is a need for an inexpensive, non invasive, quick, and simple investigation with a high sensitivity and specificity. In this study we evaluate the use of an in vivo electromagnetic (EM) interaction as a non invasive method for detecting cancer. A clinical trial was designed and completed. The main trial target was the feasibility assessment of the novel method by comparing its results with standard cystoscopy. A physical discussion of the EM interaction with bladder cancer tissue is presented. One hundred and fourteen patients referred for cystoscopy by microscopic or gross haematuria, irritative voiding symptoms, or suspected bladder tumor at ultrasound were first submitted to EM scan by means of the TRIMprob system. Cystoscopy was performed on each patient after the TRIMprob examination. Comparison between EM and cystoscopy results provides a high level of agreement (Cohen's K = 0.77, p < 0.001). The TRIMprob performance in malignant cancer cells detection suggests that this in vivo EM waves method is also worth investigating for routine diagnostic procedures.