Deliverability and efficacy of R-CHOP chemotherapy in very elderly patients with diffuse large B-cell lymphoma: an Australian retrospective analysis.

BACKGROUND: Elderly patients with diffuse large B-cell lymphoma (DLBCL) have an inferior prognosis, due in part to advanced age and pre-existing comorbidities, with reduced tolerability and deliverability of standard R-CHOP chemotherapy. AIMS: To examine the deliverability, toxicity and efficacy of R-CHOP and the prevalence of the germinal and non-germinal phenotype DLBCL in an elderly Australian cohort. METHODS: This retrospective analysis included patients ≥75 years diagnosed with DLBCL. Comprehensive chemotherapy and toxicity data were collected for patients treated with R-CHOP. Baseline demographics and chemotherapy characteristics were compared with progression-free (PFS) and overall survival (OS). Immunohistochemical staining identified the prevalence of the non-germinal centre (non-GCB) phenotype. RESULTS: Of the 111 patients, 92 (83%) commenced R-CHOP with 26/92 (28%) receiving ≤4 cycles. Median average relative dose (ARD) was 0.80 (0.07-1.17). Median average relative dose intensity (ARDI) was 0.89 (0.33-1.18). Serious adverse events occurred in 77% of patients with ≥Gd3 adverse events in 74%. Overall response rate was 85%. Two-year PFS was 63% and OS 74%. ARD and performance status ≥2 were significant prognostic factors for PFS and OS but not ARDI. Non-GCB-phenotype was identified in 44/72 (61%) of patients with immunohistochemical data. CONCLUSION: Despite high response rates and respectable survival estimates, the absence of standard therapy in 17% of patients, and dose reductions and serious toxicity of R-CHOP in this Australian cohort highlights the need for the development of less toxic yet efficacious treatments for very elderly patients with DLBCL. The high prevalence of the non-GCB phenotype highlights the potential value of targeted biological therapy for this demographic.

[Genital lymphedema associated with Crohn's disease]. / Lymphœdème génital associé à une maladie de Crohn.

INTRODUCTION: Crohn's disease is a chronic inflammatory intestinal pathology which can be associated to different extra-digestive manifestations. We reported a case of recurrent genital lymphedema leading to Crohn's disease diagnosis. CASE REPORT: A 49-year-old man was referred for increased penis and scrotal volume, associated with recurrent febrile flare during the 10 previous years. Clinically, we noted an inflammatory penis and scrotum lymphedema. Clinical urological examination, and biological, bacteriological, computer-tomography examinations were negative. Metastatic Crohn's disease was diagnosed in association with concomitant severe terminal ileitis. Treatment with corticosteroids and azathioprine resulted in significant decrease of inflammatory genital lymphedema. CONCLUSION: Genital inflammatory lymphedema occurs during inflammatory, infectious, and tumor diseases. Some cases of metastatic genital lymphedema related to Crohn's disease are described, most often in children. Inflammatory genital lymphedema associated with gastrointestinal symptoms may suggest Crohn's disease.

Prognostic factors associated with healing of venous leg ulcers: a multicentre, prospective, cohort study.

BACKGROUND: Some prognostic markers of venous leg ulcer (VLU) healing have been evaluated, mostly in retrospective studies. OBJECTIVES: To identify which clinical characteristics, among those known as possible prognostic factors of VLU healing, and which VLU-associated sociodemographic and psychological factors, are associated with complete healing at week 24 (W24). METHODS: A prospective, multicentre, cohort study was conducted in 22 French dermatology departments between September 2003 and December 2007. The end point was comparison between healed and nonhealed VLUs at W24, for patient clinical and biological characteristics; psychological, cognitive and social assessments; affected leg inclusion characteristics; venous insufficiency treatment and percentage of initial wound area reduction during follow-up. RESULTS: In total, 104 VLUs in 104 patients were included; 94 were analysed. The mean VLU area and duration were 36.8 ± 55.5 cm2 and 24.8 ± 45.7 months, respectively. At W24, 41/94 VLUs were healed. Univariate analysis significantly associated complete healing with superficial venous surgery (P = 0.001), adherence to compression therapy at W4 (P = 0.03) and W24 (P = 0.01), ankle-joint ankylosis (P = 0.01) and mean percentage of VLU area reduction at W4 (P = 0.04). Multivariate analysis retained superficial venous surgery during follow-up [odds ratio (OR) 8.4, 95% confidence interval (CI) 1.9-48.2] and percentage reduction of the VLU area at W4 (OR 1.6, 95% CI 1.0-2.14) as being independently associated with healing. CONCLUSIONS: These results indicate that complete healing of long-standing, large VLUs is independently associated with ablation of the incompetent superficial vein and percentage of wound area reduction after the first 4 weeks of treatment.

[New developments in Sézary syndrome]. / Actualités sur le syndrome de Sézary.

Sézary syndrome (SS) represents 3% of cutaneous T-cell lymphomas (CTCL). It is an aggressive epidermotropic CTCL with a 5-year survival rate of 24%. According to EORTC (European organization for research and treatment of cancer), SS is defined by erythroderma, diffuse lymphadenopathy, atypical T lymphocytes (>1000/mm(3)), and the presence of a major blood, cutaneous and nodal T cell clone. A specific marker for atypical tumoral T lymphocytes known as Sézary cells was identified in 2001, namely KIR3DL2 (CD158k) receptor, which allows more specific diagnosis of SS; levels of this marker are highly correlated with the clinical course of the disease. In therapeutic terms, clinical trials are being conducted on new molecules that point towards an improved prognosis for this disease. We propose a review of Sézary syndrome, which is currently the subject of scientific papers concerning both physiopathology and therapeutics, with new prospects of targeted therapy.

Febrile ulceronecrotic Mucha-Habermann disease: treatment with infliximab and intravenous immunoglobulins and review of the literature.

Febrile ulceronecrotic Mucha-Habermann disease (FUMHD) is a rare subtype of pityriasis lichenoides et varioliformis acuta, characterized by an acute onset of ulceronecrotic papules, rapidly coalescing into large ulcers with necrotic crusts, associated with high fever and severe systemic symptoms. We report a case of a 65-year-old woman with a resistant form of FUMHD successfully treated with a tumor necrosis factor-α (TNFα) inhibitor (infliximab). After 1 year of treatment, because of the recurrence of lesions and -occurrence of severe sepsis, we decided to change the therapeutic procedure by introducing intravenous immunoglobulin witch induced a spectacular improvement. Only few cases of FUMHD treated with intravenous immunoglobulin have been reported to date. In our case, we describe the first utilization of TNFα inhibitors in the treatment of FUMHD: TNFα inhibitors may be useful, particularly in resistant cases. Further reports are required to confirm this potential therapeutic option.

Two atypical cases of cutaneous gamma/delta T-cell lymphomas.

Cutaneous γ/δ T-cell lymphoma (CGD-TCL) is a recent entity described in the newly revised World Health Organization-European Organization for Research and Treatment of Cancer classification of cutaneous lymphomas, and is characterized by the γ/δ T-cell receptor expression on atypical lymphocytes. Only a few cases of primary CGD-TCL have been reported, with an extremely aggressive course (median survival time of 15 months). We describe 2 atypical cases of CGD-TCL. The first case was initially misdiagnosed as an inflammatory panniculitis due to the granulomatous infiltrate on the skin biopsy specimen. Diagnosis was confirmed using δ PCR that revealed γ/δ T-cell clonal expansion. The evolution was marked by predominant γ/δ T-cell infiltrate with diffuse body fat involvement as seen on positron emission tomography-computed tomography. The second case is the first described Epstein-Barr virus (EBV)-associated CGD-TCL with a rapidly fatal evolution. CGD-TCL is also a heterogeneous entity and δ PCR and EBV-encoded RNA probe to detect an EBV latent infection may help diagnose and characterize these cutaneous lymphomas.

Cutaneous sarcoidosis occurring during anti-TNF-alpha treatment: report of two cases.

We report two cases of cutaneous granuloma induced by anti-TNF-alpha therapy: a 47-year-old man suffering from psoriatic arthritis treated with infliximab and a 56-year-old woman treated with adalimumab for polyarticular juvenile rheumatoid arthritis. The biospies confirmed the diagnosis of a 'sarcoidosis-like' reaction. No systemic involvement was observed. Such cases of noninfectious granulomatous diseases occurring during anti-TNF-alpha therapy are becoming increasingly frequent.

Evidence of two contrasting brown trout Salmo trutta populations spatially separated in the River Borne (France) and shift in management towards conservation of the native lineage.

A multidisciplinary study was made of brown trout Salmo trutta in the Borne River, a typical fast-flowing mountain stream in the Northern French Alps, in the geographical range of the Mediterranean lineages (ML). Information on (1) the proportion of stocked fluoro-marked fish in the angling harvest, (2) the introgression of introduced DNA microsatellite alleles into the native gene pool and (3) the demography of the population in situ in autumn revealed two contrasting populations separated by a physical barrier to upstream migration. A native S. trutta population (c. 10 000 adults) lives downstream of the barrier and is characterized by a large frequency of ML alleles (82-97%) and high densities (43-55 fish 100 m(-2)). This population is maintained predominantly by natural recruitment of juveniles (51-82%). In contrast, the upstream population is characterized by a large frequency of Atlantic lineage (AL) alleles (78-100%) and low densities (1-2 fish 100 m(-2)) and appears to be maintained by restocking (90-100%). The origins of these sharply contrasting populations appear to reflect isolation by an impassable barrier, catastrophic flooding, a downstream gradient in water quality, stocking and fishing pressure. The native downstream population has been resilient to large sudden floods and to intensive stockings of domesticated AL fish. The results of this study justify a shift in management towards conservation and rehabilitation of the native population.

A single ascending dose study of epigallocatechin gallate in healthy volunteers.

This randomized, double-blind, placebo-controlled study assessed the safety, tolerability and plasma kinetic behaviour of single oral doses of 94% pure crystalline bulk epigallocatechin gallate (EGCG) under fasting conditions in 60 healthy male volunteers. In each group of 10 subjects, eight received oral EGCG in single doses of 50 mg, 100 mg, 200 mg, 400 mg, 800 mg or 1600 mg, and two received placebo. Blood samples were taken at intervals until 26 h later. The area under the concentration-time curve from 0 h to infinity (AUC(0-infinity)), the maximum plasma concentration (Cmax) of EGCG, the time taken to reach the maximum concentration (Tmax), and the terminal elimination half-life (t1/2z) of EGCG were determined. Safety and tolerability were assessed. In each dosage group, the kinetic profile revealed rapid absorption with a one-peak plasma concentration versus time course, followed by a multiphasic decrease consisting of a distribution phase and an elimination phase. The mean AUC(0-infinity) of total EGCG varied between 442 and 10,368 ng.h/ml. The according mean Cmax values ranged from 130 to 3392 ng/ml and were observed after 1.3-2.2 h. The mean t1/2z values were seen between 1.9 and 4.6 h. Single oral doses of EGCG up to 1600 mg were safe and very well tolerated.

Finescale topographical correlates of behavioural investment in offspring by female grey seals, Halichoerus grypus.

Grey seals breed colonially on substrates ranging from ice to rocky or sandy beaches. Clear differences in seal behaviour patterns exist among such broad classes of breeding habitat. However, finer scale topographical variation is likely to influence individual behaviour with consequences for pupping success. We examined topographical influences on the behaviour of breeding female grey seals by quantifying topography at a subseal size resolution. Using submetre resolution digital terrain models of two sites within a rocky breeding colony, we compared site topography in relation to observed differences in female behaviour at these sites. Females at both sites preferred breeding close to water (standing pools or sea) and frequently commuted between their pups and water. Topographical models indicated that one site was more costly for seals in terms of their locations and movements within the site. This was due to a lack of low-elevation land adjacent to the main access points from the sea and the reduced availability of pools. Females at this site showed reduced pup attendance and an increase in energetically costly behaviours, whilst females at the lower-cost site spent more time interacting with their pups and resting. These topographically induced behavioural differences are likely to affect the quantity and quality of pup provisioning by mothers and influence individual pupping site selection. Less costly sites are likely to be colonized preferentially and by larger, older and more dominant females, potentially generating finescale spatial heterogeneity in female quality within the breeding colony. Copyright 2000 The Association for the Study of Animal Behaviour.