Evaluation in usual practice of the bevacizumab-FOLFIRI combination for the first-line treatment of patients with unresectable metastatic colorectal cancer treated in 2006: focus on resected patients and oncogeriatrics: AVASTIN OUEST cohort of the Observatory of Cancer of the Brittany and Pays de la Loire Areas (Observatoire dédié au Cancer Bretagne / Pays de la Loire).

BACKGROUND: In 2006, bevacizumab, a targeted therapy agent was combined with FOLFIRI for the firstline treatment of patients with unresectable metastatic colorectal cancer. METHODS/RESULTS: A study on a homogenous series of 111 patients from the Brittany and Pays de la Loire areas who received bevacizumab-FOLFIRI as first-line treatment in 2006 showed the following results: 51 responses, 29 stabilisations, 21 progressions and 10 cases of toxicity prior to assessment. Median overall survival (OS) was 25.1 months and median progression-free survival was 10.2 months. Surgery secondary to treatment tripled median OS which reached 59.2 months in resected patients versus 18.8 months in unresected patients. Comparison of patients aged more or less than 70 years showed no differences in terms of benefits or risks. CONCLUSION: Bevacizumab-FOLFIRI could be administered as part of a routine care protocol to elderly patients previously evaluated by a geriatric assessment and validated by a multidisciplinary staff.

En 2006, bevacizumab-FOLFIRI représente la thérapie ciblée administrable dès la première ligne chez les patients porteurs d'un cancer colorectal métastatique non opérable. Une série homogène de 111 patients colligés en région Bretagne et Pays de la Loire ayant reçu du bevacizumab- FOLFIRI en première ligne en 2006 révèle les résultats suivants: 51 réponses, 29 stabilités, 21 progressions et 10 toxicités avant évaluation. La médiane de survie globale (OS) est de 25,1 mois et la médiane de survie sans progression (PFS) de 10,2 mois. Dans le cas d'une chirurgie secondaire, l'OS médian triple de 18,8 mois chez les patients non réséqués versus 59,2 mois ceux réséqués. En comparant les sujets âgés de plus et de moins de 70 ans, aucune différence n'a été mise en évidence en termes de bénéfice ou de risque. Bevacizumab-FOLFIRI pourrait être administré en pratique courante chez les personnes âgées sous couvert d'une évaluation gériatrique et d'une approche multidisciplinaire.

Unusual erythema elevatum diutinum with fibrohistiocytic proliferation.

A 78-year-old woman with a history of symmetrical erythematous plaques on the arms, and a monoclonal gammopathy, developed a strange striped reticulate papular dermatosis with central atrophy. Histological examination was compatible with a very late stage of erythema elevatum diutinum (EED), showing a fibrohistiocytic proliferation with areas of granulation tissue. This fibrosis may result from the chronic dermal injury of leucocytoclastic vasculitis and is sometimes the predominant histology of EED. Investigations for underlying haematological anomalies, such as paraproteinaemia and infection with human immunodeficiency virus, must be performed. Dapsone is ineffective once the fibrous nodules have appeared.

Hydroxyurea-induced dermatomyositis-like eruption.

Hydroxyurea is frequently used to treat myeloproliferative syndromes. Cutaneous lesions resembling those seen in dermatomyositis have rarely been reported in the course of treatment with hydroxyurea. We report six additional patients with this unusual adverse effect. All of the patients had a very typical and similar cutaneous eruption, with scaly, linear erythema on the dorsa of the hands. Leg ulceration occurred in two cases. Muscle involvement was never observed. One patient had unexplained lung disease. In all the others the disorder pursued a benign course, even when hydroxyurea was not withdrawn. Dermatomyositis-like lesions seem to be a not infrequent and characteristic adverse reaction to hydroxyurea. Investigations are not required, and the course is usually benign.

Antiphospholipid antibody production during Mediterranean spotted fever.

Antiphospholipid antibodies (aPLA) were discovered during the course of Mediterranean spotted fever (MSF) caused by Rickettsia conorii and characterized by endothelial cell (EC) damage resulting from this organism's tropism for EC. In two MSF patients, two types of aPLA were identified: antiphosphatidylethanolamine antibodies detected by immunological methods and lupus anticoagulant detected by clotting assays. The persistence of both aPLA for several months after the acute phase and clinical recovery might correspond to a durable immunological response to membrane damage of EC caused by R. conorii. Their possible role in the pathophysiology of microthrombi formation observed during MSF remains to be elucidated in a study on a larger number of patients.

[Syndrome of hemophagocytosis associated with infections]. / Syndrome d'hémophagocytose associé aux infections.

Infection-related hemophagocytic syndrome was originally described in viral processes by Risdall in 1979. Recent reports have suggested associations of this syndrome with bacterial, parasitic and fungal infections. It occurs generally in immunosuppressed patients. The clinical and biological manifestations are not specific. The diagnosis is based on morphologic examination of the bone marrow showing a benign proliferation of histiocytes with hemophagocytosis. Treatment is symptomatic, however when an infectious etiology is found a specific treatment must be applied. This pathology has a poor prognosis, with a fifty percent mortality rate. When evolution is favorable, relapses are exceptional. The precise pathophysiological mechanism has not yet been determined. A better understanding of the cytokines' role should permit to consider new therapeutic routes.

[Paraneoplastic edema syndromes in acute myelomonocytic leukemia: role of TNF-alpha and IL-6?]. / Syndrome oedémateux paranéoplasique au cours d'une leucémie aiguë myélomonocytaire: rôle du TNF alpha et de l'IL-6?

We report the case of a 56 year-old man in remission of a Hodgkin's disease who had an acute myelomonocytic leukemia with major edemas. Chemotherapy temporarily allowed a concomitant regression of edemas, hyperleukocytosis and tumor necrosis factor and interleukin-6 levels which were initially elevated. We discuss the role of these two cytokines in endothelium permeability disorders.

C3d,g deposits in inflammatory skin diseases: use of psoriatic skin as a model of cutaneous inflammation.

Recent studies in our laboratories have shown that human keratinocytes synthesize and secrete complement components including C3. Moreover, human keratinocyte-derived C3 is regarded as a potential source of C3d,g, a recently described constituent of the sublamina densa region of normal epidermal basement membrane. Additionally, human keratinocyte-derived C3 may also contribute to epidermal basement membrane deposits of C3 in autoimmune or inflammatory skin disorders. To further our understanding of the specificity and origin of epidermal basement membrane C3 deposits in normal and diseased skin, we have characterized in situ deposits of C3 and C3 cleavage fragments in various inflammatory skin diseases and utilized a skin equivalent model to assess the deposition of C3 cleavage fragments in neo-basement membrane of epidermal outgrowths from normal or diseased human skin. C3d,g reactivity was found to be greater in all samples of inflamed skin, and typically associated with C3c reactivity at these sites. No immunoglobulins or other complement components were detected. When lesional psoriatic skin rich in epidermal basement membrane C3c was used in our organ culture system, C3 incorporation within neo-basement membrane was observed. These results show that human keratinocyte-derived C3 may contribute to inflammatory reactions in skin as well as account for deposits of C3d,g in normal epidermal basement membrane.