Safety and efficacy of the anti-PD1 immunotherapy with nivolumab in trichoblastic carcinomas.

Trichoblastic carcinoma is a rare malignant cutaneous adnexal tumor with a risk of local invasion and distant metastasis. As of today, there is no consensus for the treatment of locally advanced or metastatic trichoblastic carcinoma. "AcSé Nivolumab" is a multi-center Phase II basket clinical trial (NCT03012581) evaluating the safety and efficacy of nivolumab in several cohorts of rare, advanced cancers. Here we report the results of nivolumab in patients with trichoblastic carcinoma. Of the eleven patients enrolled in the study, five patients had been previously treated by sonic hedgehog inhibitors. The primary endpoint 12-week objective response rate was 9.1% (N = 1/11) with 1 partial response. Six patients who progressed under previous lines of treatment showed stable disease at 12 weeks, reflecting a good control of the disease with nivolumab. Furthermore, 54.5% of the patients (N = 6/11) had their disease under control at 6 months. The 1-year overall survival was 80%, and the median progression-free survival was 8.4 months (95%CI, 5.7 to NA). With 2 responders (2 complete responses), the best response rate to nivolumab at any time was 18.2% (95%CI, 2.3-51.8%). No new safety signals were identified, and adverse events observed herein were previously described and well known with nivolumab monotherapy. These results are promising, suggesting that nivolumab might be an option for patients with advanced trichoblastic carcinomas. Further studies on larger cohorts are necessary to confirm these results and define the role of nivolumab in the treatment of trichoblastic carcinomas.

Paris MEM: a study protocol for an effectiveness and efficiency trial on the treatment of traumatic stress in France after the 2015-16 terrorist attacks.

BACKGROUND: The Paris and Nice terrorist attacks affected a thousand of trauma victims and first-line responders. Because there were concerns that this might represent the first of several attacks, there was a need to quickly enhance the local capacities to treat a large number of individuals suffering from trauma-related disorders. Since Reconsolidation Therapy (RT) is brief, relatively easy to learn, well tolerated and effective, it appeared as the ideal first-line treatment to teach to clinicians in this context. METHODS: This study protocol is a two-arm non-randomized, multicenter controlled trial, comparing RT to treatment as usual for the treatment of trauma-related disorders. RT consists of actively recalling one's traumatic event under the influence of the ß-blocker propranolol, once a week, for 10-25 min with a therapist, over 6 consecutive weeks. This protocol evaluates the feasibility, effectiveness, and cost-utility of implementing RT as part of a large multi-center (N = 400) pragmatic trial with a one-year follow-up. DISCUSSION: Paris MEM is the largest trial to date assessing the efficiency of RT in the aftermath of a large-scale man-made disaster. RT could possibly reinforce the therapeutic arsenal for the treatment of patients suffering from trauma-related disorders, not only for communities in western countries but also worldwide for terror- or disaster-stricken communities. TRIAL REGISTRATION: Clinical Trials (ClinicalTrials.gov). June 3, 2016. NCT02789982.

Why are head and neck squamous cell carcinoma diagnosed so late? Influence of health care disparities and socio-economic factors.

CONTEXT: Late stage diagnosis of Head and Neck Squamous Cell Carcinoma (HNSCC) makes the prognosis worse. However, the influence of inequalities of health care and socio-economic factors has never been investigated in this pathology. OBJECTIVES: To identify any inequalities in health care and socio-economic factors influencing late-stage diagnosis of HSNCC. DESIGN: The ASED study (Acces aux Soins avant Endoscopie Diagnostique) was a cross-sectional observational, multi-centric (19 centers) study on metropolitan French territory. Data was collected from 1st December 2010 to 30th June 2012. SETTING: Patients were included prospectively in Head and Neck Surgery departments. A self-administered form was completed by the patients at the time of ambulatory diagnostic endoscopy (38 items describing demographic, socio-economic and health care access characteristics). A second form was completed by the surgeon at the time of histological confirmation of HNSCC (11 items describing the tumor). PATIENTS: Six hundred and ninety patients aged 18 or more with a first HNSCC were included. Exclusion criteria were second HSNCC or loco-regional recurrence of HNSCC. MAIN OUTCOME MEASURE(S): Late-stage was defined as T3/T4 tumor, and early-stage was defined as T1/T2 tumor, according to the TNM classification. RESULTS: Independent factors associated with late-stage diagnosis were: hypopharyngeal location (OR=3.5 [1.8-7.3] versus oral cavity location), age (OR=1.02 [1.00-1.04]), male sex (OR=1.7 [1.1-2.6]) and being born in France (OR=2 [1.2-3.3]). Factors associated with early-stage diagnosis were previous consultation to a specialist physician (OR=0.5 [0.4-0.8]), ease of access to this specialist (OR=0.6 [0.4-0.9]), and having a health professional in close contact (OR=0.6 [0.4-0.8]). Time to consultation was identical in both groups. No significant association was found between socio-economic factors (especially deprivation or alcohol and tobacco consumption) and late-stage diagnosis of HNSCC. CONCLUSION: Health care access in France plays a major role in the stage of HNSCC at diagnosis. Easy access to a specialist protects from late-stage diagnosis. Absence of socio-economic factors may be due to the French social security system and its comprehensive coverage of the population.

Second malignancies after breast cancer: the impact of different treatment modalities.

Treatment for non-metastatic breast cancer (BC) may be the cause of second malignancies in long-term survivors. Our aim was to investigate whether survivors present a higher risk of malignancy than the general population according to treatment received. We analysed data for 16 705 BC survivors treated at the Curie Institute (1981-1997) by either chemotherapy (various regimens), radiotherapy (high-energy photons from a 60Co unit or linear accelerator) and/or hormone therapy (2-5 years of tamoxifen). We calculated age-standardized incidence ratios (SIRs) for each malignancy, using data for the general French population from five regional registries. At a median follow-up 10.5 years, 709 patients had developed a second malignancy. The greatest increases in risk were for leukaemia (SIR: 2.07 (1.52-2.75)), ovarian cancer (SIR: 1.6 (1.27-2.04)) and gynaecological (cervical/endometrial) cancer (SIR: 1.6 (1.34-1.89); P<0.0001). The SIR for gastrointestinal cancer, the most common malignancy, was 0.82 (0.70-0.95; P<0.007). The increase in leukaemia was most strongly related to chemotherapy and that in gynaecological cancers to hormone therapy. Radiotherapy alone also had a significant, although lesser, effect on leukaemia and gynaecological cancer incidence. The increased risk of sarcomas and lung cancer was attributed to radiotherapy. No increased risk was observed for malignant melanoma, lymphoma, genitourinary, thyroid or head and neck cancer. There is a significantly increased risk of several kinds of second malignancy in women treated for BC, compared with the general population. This increase may be related to adjuvant treatment in some cases. However, the absolute risk is small.

Remission from Kaposi's sarcoma on HAART is associated with suppression of HIV replication and is independent of protease inhibitor therapy.

Highly active antiretroviral therapy (HAART) reduces the incidence and improves the prognosis of Kaposi's sarcoma (KS). This study was designed to identify factors associated with KS clinical responses in HIV-infected patients during HAART. We reviewed the files of 138 HIV-1-infected patients with KS. Epidemiologic and HIV-related clinical and biological parameters were recorded at KS diagnosis (baseline) and every 6 months thereafter. In a subset of 73 antiretroviral-naive patients, we compared the clinical outcome of KS according to the use or nonuse of protease inhibitors (PI). After 6 months of follow-up, KS remission was more frequent in patients who were naive of HAART and who were at ACTG stage S0 at baseline (P = 0.03 and 0.02). Undetectable HIV viral load was strongly associated with KS remission (P< or = 0.004 at all time points), while CD4 cell count was not. Among the 73 antiretroviral-naive patients at baseline, and who were studied for 24 months, KS outcome did not differ between patients who were prescribed PI-containing and PI-sparing regimens. Intercurrent multicentric Castleman's disease was associated with poor outcome after 60 months of follow-up (P< or = 0.0001). Fourteen deaths occurred after a median follow-up of 37.5 months, eight of which were KS related. Suppression of HIV replication appears to be crucial to control KS. Non-PI-based regimens were equivalent to PI-based regimens as regards the clinical and virological outcome of antiretroviral-naive HIV-infected patients with KS.

Acute hepatitis C infection in HIV positive men who have sex with men in Paris, France, 2001-2004.

In mid-2004, three Parisian hospital wards informed the Institut de veille sanitaire of recent acute hepatitis C in HIV-infected (HIV+) men who had sex with men (MSM). These cases for whom none of the usual bloodborne routes for hepatitis C (HCV) transmission was found, reported having had unprotected sex. In October 2004, we conducted a retrospective investigation in Parisian hospital wards to explore HCV modes of transmission in recent acute hepatitis C in HIV+ MSM. Patient demographics, clinical and biological status of HIV infection, reasons for HCV testing, sexual behaviour and risk factors for HCV transmission within the 6 months before hepatitis onset were collected from medical records. An anonymous self-administered questionnaire on sexual behaviour within the six months before hepatitis onset was also offered to all cases. We identified 29 cases of acute hepatitis C in HIV+ MSM with onset from April 2001 to October 2004. HIV infection was asymptomatic for 76%. Median age at hepatitis C onset was 40 (28-54) years. In all records, were noted unprotected anal sex, fisting in 21% and a concomitant sexually transmitted infection (STI) in 41%. Median time between HIV diagnosis and HCV infection was 6.5 years (0-22). From the 11 self-administered questionnaires completed, 10 reported an STI, 8 'hard' sexual practices, 6 bleeding during sex and 5 fisting. HCV transmission probably occurred through bleeding during unprotected traumatic anal sex among HIV+ MSM and may be facilitated by STI mucosal lesions. This report stresses the continuous need to strongly advocate safer sex to MSM.

Acute hepatitis C infection in HIV positive men who have sex with men in Paris, France, 2001-2004.

In mid-2004, three Parisian hospital wards informed the Institut de veille sanitaire of recent acute hepatitis C in HIV-infected (HIV+) men who had sex with men (MSM). These cases for whom none of the usual bloodborne routes for hepatitis C (HCV) transmission was found, reported having had unprotected sex. In October 2004, we conducted a retrospective investigation in Parisian hospital wards to explore HCV modes of transmission in recent acute hepatitis C in HIV+ MSM. Patient demographics, clinical and biological status of HIV infection, reasons for HCV testing, sexual behaviour and risk factors for HCV transmission within the 6 months before hepatitis onset were collected from medical records. An anonymous self-administered questionnaire on sexual behaviour within the six months before hepatitis onset was also offered to all cases. We identified 29 cases of acute hepatitis C in HIV+ MSM with onset from April 2001 to October 2004. HIV infection was asymptomatic for 76%. Median age at hepatitis C onset was 40 (28-54) years. In all records, were noted unprotected anal sex, fisting in 21% and a concomitant sexually transmitted infection (STI) in 41%. Median time between HIV diagnosis and HCV infection was 6.5 years (0-22). From the 11 self-administered questionnaires completed, 10 reported an STI, 8 "hard" sexual practices, 6 bleeding during sex and 5 fisting. HCV transmission probably occurred through bleeding during unprotected traumatic anal sex among HIV+ MSM and may be facilitated by STI mucosal lesions. This report stresses the continuous need to strongly advocate safer sex to MSM.

[Factors associated with the late management of HIV-infected patients: literature review]. / Facteurs associés à une prise en charge tardive des patients infectés par le VIH: revue de la littérature.

In the United States, Australia and Europe, many HIV infected individuals are still diagnosed and/or treated late in the course of the disease. This literature review of studies published over a ten year period between 1993 and 2003 has identified the following principle factors associated with the late diagnosis of HIV: male gender, aged older than 45 years, heterosexual intercourse, the lack of previous screening. It also identified the factors linked to the delay in beginning anti-retroviral treatment as being male gender, the lack of awareness or denial of the possibility of HIV infection, intravenous drug use, lack of post-screening follow-up or counseling, lack of social protection, and the lack of regular medical visits and care. Early detection and suitable early treatment of the HIV virus are the main determining factors which will effectively contribute to the control and maintenance of the virus in as much as they are focused upon these particular at-risk populations.

Safety of percutaneous internal jugular catheterization in cancer patients: prospective observational study.

PURPOSE: To determine predictors for failure and early complications of percutaneous internal jugular catheterization (IJC) in cancer patients. METHODS: Six hundred and thirty consecutive cancer patients who required central venous catheterization were included in a prospective observational study. The rates of failure (defined as the intervention of a second physician and/or failure at initial insertion site) and of early complications were prospectively ascertained. Logistic regression analysis estimated odds ratio (OR) and 95% confidence intervals (95% CI) for independent predictors for failure and early complications of percutaneous IJC. RESULTS: The failure rate was 6.7%, and the early complication rate was 6.7%. In multivariate analysis, left-side initial catheterization (p<0.01), prior catheterization at the same site (p=0.001) and physician inexperience (p<0.0001) were independently associated with failure. Placement requiring more than one needle pass (p<0.01 for two and p<0.0001 for three and more) and absence of fluoroscopy (p<0.0001) were independently associated with early complications. CONCLUSIONS: Percutaneous IJC is a valid option in the central venous catheterization of cancer patients due to its reliability and safety. Skilled physicians must manage difficult placements. If placement requires more than one needle pass or is made without fluoroscopy, patients must be carefully followed for potential complications.