Trichophyton indotineae, from epidemiology to therapeutic.

Trichophyton indotineae is a newly described dermatophyte species. This fungal pathogen has recently emerged in India and is responsible for chronic or recurrent widespread superficial infections. Resistance to terbinafine is frequently associated to this pathogen and is related to point mutations in the gene encoding the squalene epoxidase. T. indotineae infections have been reported outside India, highlighting the risk of worldwide diffusion of this microorganism. Species identification and antifungal susceptibility determination are key points for infection control but still remain challenging. Systemic treatment is usually required and itraconazole is frequently prescribed in case of terbinafine resistance. This review summarizes main features of T. indotineae taxonomy, epidemiology, clinical manifestations, identification, antifungal profile, treatment and prevention.

French recommendations on strategies for preventing and treating osteoporosis induced by adjuvant breast cancer therapies.

Standard adjuvant therapies for breast cancer such as chemotherapy or aromatase inhibitor and LH-RH agonist hormone therapy are associated with significant survival gains but also induce bone loss by aggravating the estrogen deprivation. The bone loss may be substantial, notably during early treatment, and occurs regardless of the baseline bone mineral density values. The objective of developing these recommendations was to achieve a practical consensus among various scientific societies, based on literature review, about osteoporosis prevention and treatment in these patients. The following scientific societies contributed to the work: Société Française de Rhumatologie (SFR), Groupe de Recherche et d'Information sur les Ostéoporoses (GRIO), Groupe Européen d'Etudes des Métastases Osseuses (GEMO), Association Francophone pour les Soins Oncologiques de Support (AFSOS), Société Française de Sénologie et de Pathologie Mammaire (SFSPM), Société Française de Radiothérapie Oncologique (SFRO). Drug prescription and reimbursement modalities in France were taken into account. These recommendations apply to postmenopausal women taking systemic chemotherapy and/or aromatase inhibitor therapy, non-postmenopausal women taking LH-RH agonist therapy, and non-postmenopausal women with persistent amenorrhea 1 year after chemotherapy completion. All women in these three categories should undergo an evaluation of bone health and receive interventions to combat risk factors for bone loss. Patients with a history of severe osteoporotic fracture and/or a T-score value <-2.5 should receive osteoporosis drug therapy. The FRAX® score should be used to guide treatment decisions in patients whose T-score is between -1 and -2.5. General osteoporosis prevention measures should be applied in patients without criteria for osteoporosis drug therapy, who should undergo bone mineral density measurements 18-24 months later if the baseline T-score is<-1 and 3-5 years later if the baseline T-score is>-1. The anti-tumor effect of bisphosphonates and denosumab was not considered when establishing these recommendations.

Urinary function and quality of life after radiotherapy for prostate cancer in patients with prior history of surgical treatment for benign prostatic hyperplasia.

BACKGROUND: To evaluate long-term IPSS score and urinary quality of life after radiotherapy for prostate cancer, in patients with prior history of surgical treatment for benign prostatic hyperplasia (BPH). METHODS: In this retrospective study, we reviewed medical records of patients treated in our department, between 2007 and 2013 with surgery for BPH followed by radiotherapy for localized prostate cancer. Patients were contacted to fill in IPSS questionnaire and they were also asked for urinary quality of life. Predictive factors known to be associated with bad urinary function were also analysed. RESULTS: Fifty-nine patients were included in our study. Median age was 70 years. Median follow-up was 4.6 years. Median radiotherapy dose was 78 Gy (5 × 2 Gy/week). Thirty patients (48.5%) received hormone therapy in combination with RT. Main surgery indications were urinary symptoms (65%) and urinary retention (20%). Five-year biochemical-disease free survival was 75% and 5-year clinical relapse free survival was 84%. At the time of the study, the IPSS after radiotherapy was as follows: 0-7: 77.6%; 8-19:20.7%; 20-35: 1.7%. Urinary quality of life was satisfactory for 74.2% of patients. After multivariate analysis, a high dose of RT and a medical history of hypertension were associated with a poorer quality of urinary life (p = 0.04). CONCLUSION: External radiotherapy remains an appropriate treatment option without a major risk for deterioration in urinary function in patient with antecedent surgery for BPH. High dose of RT and a medical history of hypertension were associated with a poorer quality of urinary life.

Invasive Trichosporon Infection: a Systematic Review on a Re-emerging Fungal Pathogen.

Objectives: This review aimed to better depict the clinical features and address the issue of therapeutic management of Trichosporon deep-seated infections. Methods: We comprehensively reviewed the cases of invasive Trichosporon infection reported in the literature from 1994 (date of taxonomic modification) to 2015. Data from antifungal susceptibility testing (AST) studies were also analyzed. Results: Two hundred and three cases were retained and split into four groups: homeopathy (n = 79), other immunodeficiency conditions (n = 41), miscellaneous (n = 58) and newborns (n = 25). Trichosporon asahii was the main causative species (46.7%) and may exhibit cross-resistance to different antifungal classes. The unfavorable outcome rate was at 44.3%. By multivariate analysis, breakthrough infection (OR 2.45) was associated with unfavorable outcome, whilst the use of an azole-based therapy improved the prognosis (OR 0.16). Voriconazole-based treatment was associated with favorable outcome in hematological patients (73.6 vs. 41.8%; p = 0.016). Compiled data from AST demonstrated that (i) T. asahii exhibits the highest MICs to amphotericin B and (ii) voriconazole has the best in vitro efficacy against clinical isolates of Trichosporon spp. Conclusions:Trichosporon infection is not only restricted to hematological patients. Analysis of compiled data from AST and clinical outcome support the use of voriconazole as first line therapy.

Management of Node Only Recurrence after Primary Local Treatment for Prostate Cancer: A Systematic Review of the Literature.

PURPOSE: We analyzed all available studies assessing the management of node only recurrence after primary local treatment of prostate cancer. MATERIALS AND METHODS: We systematically reviewed the literature in January 2015 using the PubMed, Web of Sciences and Embase databases according to PRISMA guidelines. Studies exclusively reporting visceral or bone metastatic disease were excluded from analysis. Eight radiotherapy and 12 salvage lymph node dissection series were included in our qualitative study. RESULTS: All 248 radiotherapy and 480 salvage lymph node dissection studies were single arm case series including a total of 728 patients. Choline positron emission tomography/computerized tomography was the reference imaging technique for nodal recurrence detection. Globally 50% of patients remained disease-free after short-term followup. Nevertheless, approximately two-thirds of patients received adjuvant hormone therapy, leading an overestimation of prostate specific antigen-free survival rates obtained after salvage treatment. Combining radiotherapy with salvage lymph node dissection may improve oncologic control in the treated region without improving the outfield relapse risk or the prostate specific antigen response. Great heterogeneity among series in adjuvant treatments, endpoints, progression definitions and study populations made it difficult to assess the precise impact of salvage treatment on the prostate specific antigen response and compare outcomes between radiotherapy and salvage lymph node dissection series. Toxicity after radiotherapy or salvage lymph node dissection was acceptable without frequent high grade complications. The benefit of early hormone therapy as the only salvage treatment remains unknown. CONCLUSIONS: Although a high level of evidence is currently missing to draw any strong conclusion, published clinical series show that in select patients salvage treatment directed to nodal recurrence could lead to good oncologic outcomes. Although the optimal timing of androgen deprivation therapy in this setting is still unknown, such an approach could delay time to systemic treatment with an acceptable safety profile. Future prospective trials are awaited to better clarify this potential impact on well-defined endpoints.

Clinical outcome of the ACCORD 12/0405 PRODIGE 2 randomized trial in rectal cancer.

PURPOSE: The ACCORD 12 trial investigated the value of two different preoperative chemoradiotherapy (CT-RT) regimens in T3-4 Nx M0 resectable rectal cancer. Clinical results are reported after follow-up of 3 years. PATIENTS AND METHODS: Between November 2005 and July 2008, a total of 598 patients were randomly assigned to preoperative CT-RT with CAP45 (45-Gy RT for 5 weeks with concurrent capecitabine) or CAPOX50 (50-Gy RT for 5 weeks with concurrent capecitabine and oxaliplatin). Total mesorectal excision was planned 6 weeks after CT-RT. The primary end point was sterilization of the operative specimen, which was achieved in 13.9% versus 19.2% of patients, respectively (P = .09). Clinical results were analyzed for all randomly assigned patients according to the intention-to-treat principle. RESULTS: At 3 years, there was no significant difference between CAP45 and CAPOX50 (cumulative incidence of local recurrence, 6.1% v 4.4%; overall survival, 87.6% v 88.3%; disease-free survival, 67.9% v 72.7%). Grade 3 to 4 toxicity was reported in four patients in the CAP45 group and in two patients in the CAPOX50 group. Bowel continence, erectile dysfunction, and social life disturbance were not different between groups. In multivariate analysis, the sterilization rate (Dworak score) of the operative specimen was the main significant prognostic factor (hazard ratio, 0.32; 95% CI, 0.21 to 0.50). CONCLUSION: At 3 years, no significant difference in clinical outcome was achieved with the intensified CAPOX regimen. When compared with other recent randomized trials, these results indicate that concurrent administration of oxaliplatin and RT is not recommended.

Postoperative chemotherapy followed by conformal concomitant chemoradiotherapy in high-risk gastric cancer.

PURPOSE: To analyze the efficacy, toxicity, and pattern of relapse after adjuvant cisplatin-based chemotherapy followed by three-dimensional irradiation and concomitant LV5FU2 chemotherapy (high-dose leucovorin and 5-fluorouracil bolus plus continuous infusion) in the treatment of completely resected high-risk gastric cancer. METHODS AND MATERIALS: This was a retrospective analysis of 52 patients with high-risk gastric cancer initially treated by total/partial gastrectomy and lymphadenectomy between January 2002 and June 2007. Median age was 54 years (range, 36-75 years). Postoperative treatment consisted of 5-fluorouracil and cisplatin chemotherapy. Adjuvant chemotherapy was followed by three-dimensional conformal radiotherapy in the tumor bed and regional lymph nodes at 4500 cGy/25 fractions in association with concomitant chemotherapy. Concomitant chemotherapy consisted of a 2-h infusion of leucovorin (200 mg/m²) followed by a bolus of 5-fluorouracil (400 mg/m²) and then a 44-h continuous infusion of 5-fluorouracil (2400-3600 mg/m²) given every 14 days, for three cycles (LV5FU2 protocol). RESULTS: Five-year overall and disease-free survival were 50% and 48%, respectively. Distant metastases and peritoneal spread were the most frequent sites of relapse (37% each). After multivariate analysis, only pathologic nodal status was significantly associated with disease-free and overall survival. Acute toxicities were essentially gastrointestinal and hematologic. One myocardial infarction and one pulmonary embolism were also reported. Eighteen patients had a radiotherapy program interruption because of acute toxicity. All patients but 2 have completed radiotherapy. CONCLUSION: Postoperative cisplatin-based chemotherapy followed by conformal radiotherapy in association with concurrent 5-fluorouracil seemed to be feasible and resulted in successful locoregional control.

Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-Prodige 2.

PURPOSE: Neoadjuvant chemoradiotherapy is considered a standard approach for T3-4 M0 rectal cancer. In this situation, we compared neoadjuvant radiotherapy plus capecitabine with dose-intensified radiotherapy plus capecitabine and oxaliplatin. PATIENTS AND METHODS: We randomly assigned patients to receive 5 weeks of treatment with radiotherapy 45 Gy/25 fractions with concurrent capecitabine 800 mg/m(2) twice daily 5 days per week (Cap 45) or radiotherapy 50 Gy/25 fractions with capecitabine 800 mg/m(2) twice daily 5 days per week and oxaliplatin 50 mg/m(2) once weekly (Capox 50). The primary end point was complete sterilization of the operative specimen (ypCR). RESULTS: Five hundred ninety-eight patients were randomly assigned to receive Cap 45 (n = 299) or Capox 50 (n = 299). More preoperative grade 3 to 4 toxicity occurred in the Capox 50 group (25 v 1%; P < .001). Surgery was performed in 98% of patients in both groups. There were no differences between groups in the rate of conservative surgery (75%) or postoperative deaths at 60 days (0.3%). The ypCR rate was 13.9% with Cap 45 and 19.2% with Capox 50 (P = .09). When ypCR was combined with yp few residual cells, the rate was respectively 28.9% with Cap 45 and 39.4% with Capox 50 (P = .008). The rate of positive circumferential rectal margins (between 0 and 2 mm) was 19.3% with Cap 45 and 9.9% with Capox 50 (P = .02). CONCLUSION: The benefit of oxaliplatin was not demonstrated and this drug should not be used with concurrent irradiation. Cap 50 merits investigation for T3-4 rectal cancers.

Growth inhibition by STI571 in combination with radiation in human chronic myelogenous leukemia K562 cells.

Altered radiation responses by STI571 (Imatinib, Glivec), a specific inhibitor of the tyrosine kinase activity of Bcr-Abl, was assessed in K562 chronic myelogenous leukemia cells using growth inhibition and colony formation assays. Flow cytometry, Western blotting, and microscope observation were used to determine cell cycle redistribution, erythroid differentiation, apoptosis, necrosis, senescence, and expression and phosphorylation of effectors downstream from Bcr-Abl as endpoints. STI571 (> or =24-h contact) retarded the growth of K562 cells and elicited reduction in the G(2)-phase content due to an efficient arrest in early S phase rather than to the disruption of the G(2) checkpoint as confirmed by analysis of Lyn and CDK1 phosphorylation. STI571 brought about the inhibitory dephosphorylation of Bcr-Abl and STAT5, but the expression of DNA-PKcs and Rad51 was unaffected and the interaction between radiation and STI571 was strictly additive with regard to induction of apoptosis. Overall STI571 interacted cooperatively with radiation to retard the growth of K562 cells but did not affect intrinsic radiosensitivity. However, STI571 and radiation acted antagonistically with each other with regard to induction of senescence and erythroid differentiation.

Anal carcinomas in HIV-positive patients: high-dose chemoradiotherapy is feasible in the era of highly active antiretroviral therapy.

BACKGROUND: Anal carcinoma, a common disease in HIV-positive patients, is usually treated with chemoradiotherapy. Generally tolerance was poor before the availability of highly active antiretroviral therapies. We report our experience of treating anal carcinoma in the era of new antiviral drugs. PATIENTS AND METHODS: Between 1997 and 2001, nine men on highly active antiretroviral therapies with good immune status before chemoradiotherapy received concomitant chemoradiotherapy consisting of 5-fluorouracil and cisplatinum, and high-dose radiotherapy (60-70 Gy) for anal carcinoma. Six cancers were Stage I, two were Stage II, and one was Stage III. CD4+ cell counts were <200/ml for four patients, between 200/ml and 500/ml for four, and >500/ml for one. RESULTS: All patients received the planned dose of radiation (> or = 60 Gy). The chemotherapy dose was reduced 25 percent in six patients. Overall treatment time was 58 days. Grade 3 hematologic or skin toxicity occurred in four patients. No association was observed between high-grade toxicity and CD4+ cell count. None of the patients developed opportunistic infections during follow-up. Eight patients were disease-free after a median follow-up of 33 months. Among them, four had no or minor anal function impairment at the last follow-up visit. One patient with T4N2 disease relapsed locally one year after treatment and underwent salvage abdominoperineal excision. CONCLUSION: High-dose chemoradiotherapy for anal carcinomas is feasible with low toxicity in HIV-positive patients treated with highly active antiretroviral therapies. Local control is similar to that obtained for HIV-negative patients.