Liver transplantation for hepatocellular carcinoma]

Hepatocellular carcinoma (HCC) is the most frequent primitive cancer of the liver. It mostly develops on cirrhotic livers. Orthotopic liver transplantation is the only treatment that definitively addresses both the metachronous occurrence risk of HCC and the underlying disease. Under Milan criteria, i.e. less than 3 nodules of 3 cm max in diameter, or 1 nodule of 5 cm maximum, OLT has been shown effective and provides with survival rates almost equal to those obtained with HCC free cirrhotic patients. In Rennes, 195 patients with early HCC on cirrhotic livers have been transplanted from January 1995 to June 2005. Global and disease free 8 years patient survival rates were 73 and 70%, respectively. These results were significantly altered when the recipient was female, the cirrhosis due to C virus and the patient of B blood group. Despite these excellent results, the principal limit to the application of transplantation for HCC remains the long period of time patients have to wait for a graft. During this period of time, growth of the tumour may drop the patient out of Milan criteria and subsequently from the waiting list. The role of chemoembolisation, liver resection and thermal ablation while the patient is waiting for a graft remains debatable.     

Determination of breast cancer prognosis after neoadjuvant chemotherapy: comparison of Residual Cancer Burden (RCB) and Neo-Bioscore

Background To compare RCB (Residual Cancer Burden) and Neo-Bioscore in terms of prognostic performance and see if adding pathological variables improve these scores.Methods We analysed 750 female patients with invasive breast cancer (BC) treated with neoadjuvant chemotherapy (NAC) at Institut Curie between 2002 and 2012. Scores were compared in global population and by BC subtype using Akaike information criterion (AIC), C-Index (concordance index), calibration curves and after adding lymphovascular invasion (LVI) and pre-/post-NAC TILs levels.Results RCB and Neo-Bioscore were significantly associated to disease-free and overall survival in global population and for triple-negative BC. RCB had the lowest AICs in every BC subtype, corresponding to a better prognostic performance. In global population, C-Index values were poor for RCB (0.66; CI [0.61–0.71]) and fair for Neo-Bioscore (0.70; CI [0.65–0.75]). Scores were well calibrated in global population, but RCB yielded better prognostic performances in each BC subtype. Concordance between the two scores was poor. Adding LVI and TILs improved the performance of both scores.Conclusions Although RCB and Neo-Bioscore had similar prognostic performances, RCB showed better performance in BC subtypes, especially in luminal and TNBC. By generating fewer prognostic categories, RCB enables an easier use in everyday clinical practice.Subject terms: Breast cancer, Breast cancer, Chemotherapy     

Effects of interleukin-2 therapy combined with highly active antiretroviral therapy on immune restoration in HIV-1 infection: a randomized controlled trial

BACKGROUND: Intermittent interleukin-2 (IL-2) therapy leads to a sustained increase of CD4 T cells in HIV-1-infected patients. METHODS: Symptom-free HIV-1-infected patients who were naive to all antiretroviral drugs (n = 68) and/or to protease inhibitors (n = 50) and had a CD4 cell count of 200-550 x 10(6) cells/l were randomly assigned to start lamivudine/stavudine/indinavir alone (controls) or combined from week 4 with subcutaneous IL-2 (5 x 10(6) IU twice daily for 5 days: every 4 weeks for three cycles, then every 8 weeks for seven cycles). Immunological and virological results were monitored until week 74. RESULTS: CD4 T cell counts increased more in the IL-2 group than in the controls (median increases 865 and 262 x 10(6) cells/l, respectively; P < 0.0001); an 80% increase in CD4 T cells was achieving by 89% of the IL-2 group and by 47% of the controls (P < 0.0001). Decrease of plasma viral loads was similar in both groups. Compared with controls, IL-2 induced a greater increase of naive and memory CD4 T cells, lymphocyte expression of CD28 and CD25 (P < 0.0001) and natural killer cells (P < 0.001). In a logistic regression analysis, odds of being responders to recall antigens was 8.5-fold higher in IL-2 recipients (P = 0.002) than in controls. The former experienced a higher level of antibody response to tetanus vaccination at week 64 than controls (32 and 8 haemagglutinating units/ml, respectively; P = 0.01). CONCLUSIONS: The combination of antiviral drugs and IL-2 induced a greater expansion and function of CD4 T cells than antiretroviral drugs alone.     

New insights on IgA vasculitis with underlying solid tumor: a nationwide French study of 30 patients

Clinical Rheumatology - IgA vasculitis (IgAV) frequently occurs during or after a mucosal infection; it also rarely occurs in patients with cancer. We hypothesized that cancer could impact the...     

Targeting NF-kappaB in Waldenstrom macroglobulinemia

The nuclear factor-B (NF-B) path-way has been implicated in tumor B-cell survival, growth, and resistance to therapy. Because tumor cells overcome single-agent antitumor activity, we hypothesized that combination of agents that target differentially NF-B pathway will induce significant cytotoxicity. Therapeutic agents that target proteasome and Akt pathways should induce significant activity in B-cell malignancies as both pathways impact NF-B activity. We demonstrated that perifosine and bortezomib both targeted NF-B through its recruitment to the promoter of its target gene IB using chromatin immunoprecipitation assay. This combination led to synergistic cytotoxicity in Waldenstrom macroglobulinemia (WM) cells that was mediated through a combined reduction of the PI3K/Akt and ERK signaling pathways, found to be critical for survival of WM cells. Moreover, a combination of these drugs with the CD20 monoclonal antibody rituximab further increased their cytotoxic activity. Thus, effective WM therapy may require combination regimens targeting the NF-B pathway.      

Lessons from joint development for cartilage repair in the clinic

More than 250 years ago, William Hunter stated that when cartilage is destroyed it never recovers. In the last 20 years, the understanding of the mechanisms that lead to joint formation and the knowledge that some of these mechanisms are reactivated in the homeostatic responses of cartilage to injury has offered an unprecedented therapeutic opportunity to achieve cartilage regeneration. Very large investments in ambitious clinical trials are finally revealing that, although we do not have perfect medicines yet, disease modification is a feasible possibility for human osteoarthritis.