Louis Descos

Effective use of argon plasma coagulation in the treatment of severe radiation proctitis

PURPOSE: Chronic radiation proctitis, a well described complication of pelvic radiation therapy, can result in severe bleeding that is refractory to conventional treatment. Argon plasma coagulation is an effective treatment for hemorrhagic lesions of the gastrointestinal tract. The aim of this study was to assess the efficacy and safety of argon plasma coagulation in the management of severe radiation proctitis resistant to medical treatment. METHODS: Eleven patients (10 males) aged between 54 and 86 years (mean ± standard error of the mean, 73±3.years), with chronic radiation proctitis after radiotherapy for prostate (n=9), uterine (n=1) or rectal (n=1) cancer were enrolled in this prospective study. Traditional therapies had failed including mainly topical steroids, 5-aminosalicylic acid and sometimes sucralfate. All patients had active bleeding from diffuse telangiectasias responsible for chronic anemia and seven of them required blood transfusions. The mean duration of the sessions was 20 minutes and one to five sessions (mean, 3.2±0.4), usually without anesthesia, were required to stop bleeding. Mean follow-up time was 19±2 (range, 7–30) months. RESULTS: Rectal bleeding disappeared in nine patients and was greatly reduced in two. All the patients were free of transfusions during the mean follow-up of 19 months. The mean hemoglobin level was 7.7±2.8 g/dl at the first session and increased significantly (P=0.003) to 11.5±2.6 g/dl after treatment. In two patients, a rectal stenosis appeared 7 and 11 months after the first session. CONCLUSION: Argon plasma coagulation is a simple, inexpensive and effective treatment for severe refractory radiation proctitis with telangiectasias. Follow-up supervision is in progress to evaluate long term benefits and the risk of rectal stenosis.

Management for severe Crohn's disease: A lifetime cost-utility analysis

OBJECTIVES Infliximab is a costly therapy for active Crohns disease resistant to corticosteroids and immunosuppressive medication. The purpose of this study was to examine whether a treatment including infliximab (episodic re-infusions for relapse or maintenance therapy every 8 weeks) was relevant compared with conventional management (surgery and medical treatment without infliximab) for nonfistulizing resistant Crohns disease. METHODS We performed a life-time cost-utility analysis with an analytic Markov decision model from the perspective of the third-party payer system. Utility measurement using Standard Gamble was used to adjust the survival time for each health state of the disease. Direct costs were estimated from standard management based on expert opinion. A sensitivity analysis was conducted to gauge the effects of uncertainty in the values assigned to variables. RESULTS The incremental effectiveness with infliximab therapy is .761 Quality-Adjusted Life Years (QALYs) for an added cost ranging from 48,478.79 euros to 596,990.35 euros, depending on treatment procedure. The incremental cost utility ratio expressed in euros per QALYs saved varied from 63,700.82 euros (episodic re-infusions) to over 762,245.09 euros (maintenance therapy). CONCLUSIONS Infliximab therapy could be cost-effective in the case of relapse treatment only, whereas the marginal cost-utility ratio exceeds conventional benchmarks for maintenance therapy. This analysis will be supplemented by conducting further randomized controlled trials and prospective observational study, focused on the costs of illness (direct and indirect), patient preferences, the diseases clinical course, and infliximab safety.

Butyrate strongly inhibits in vitro stimulated release of cytokines in blood.

We studied the in vitro effects of butyrate on the stimulated release of proinflammatory cytokines and cytokines involved in the Th-1/Th-2 balance using the whole-blood model in nine healthy humans. Cytokines were measured without (control) and after stimulation by bacterial lipopolysaccharides (LPS) and phytohemagglutinin (PHA) alone or with addition of butyrate at six different concentrations (0.0625, 0.125, 0.25, 0.5, 1, and 2 mM). We found that butyrate at the six tested concentrations induced a significant decrease (P < 0.001) in the stimulated release of TNF-α, IFN-γ, and IL-12, whereas IL-6 release was not altered. At concentrations ≥0.25 mM, butyrate significantly reduced the stimulated release of IL-5, IL-10, and IL-13; the stimulated release of IFN-γ, IL-12, IL-5, and IL-13 was nearly abolished when compared to the unstimulated control sample. We concluded that butyrate has a wide spectrum of inhibitory activity on cytokine release stimulated by LPS + PHA in a whole-blood model. Confirmation of these results on colonic samples would show that butyrate is a factor by which the luminal contents may modulate the immune system in order to maintain the colonic mucosa in a noninflammatory state.

Exogenous oestrogen as an alternative to food allergy in the aetiology of angioneurotic oedema.

Although frequently reported as an aetiology for chronic angioneurotic oedema or urticaria, food allergy is often a diagnosis proposed in the absence of more convincing evidence, as illustrated by the disappointing results of eviction regimens. We report a series of women with an initial diagnosis of food allergy, but in whom the role of oral contraceptives was subsequently demonstrated. Detailed medical history was obtained from 26 young women presenting with chronic angioneurotic oedema or urticaria initially attributed to food allergy, but in whom C1-esterase inhibitor (C1 INH) deficiency was demonstrated. We investigated the effects of oral contraception on C1 INH levels, C1 INH activity and clinical symptoms of these patients. Discontinuation of oral contraception induced an increase in C1 INH levels and C1 INH activity, associated with recovery or marked improvement of the clinical symptoms formerly attributed to food allergy. The relatively high frequency of women taking cyproterone acetate in this population appeared to be a remarkable finding. Replacement of the initial contraception containing ethinylestradiol by a progestogen maintained or even accentuated these good therapeutic results. Exogenous oestrogens, such as those contained in most oral contraceptives, may play an iatrogenic role in the aetiology of chronic angioneurotic oedema or urticaria.

Assessment of Appropriate Laboratory Measurements to Reflect the Degree of Activity of Ulcerative Colitis

Eleven laboratory parameters were compared with the clinical grading of disease activity in 44 patients with ulcerative colitis, using multiple stepwise regression analysis to identify which measurements significantly reflect the severity of the disease. Only 2 parameters, serum orosomucoid and haematocrit showed significant correlation with clinical status. It is suggested that in the method of assessing disease activity proposed by Truelove and Witts the haemoglobin, which in this study was found to have no value, could be replaced by an equally simple test, the haematocrit. Comparisons are made between the relative usefulness of these parameters in ulcerative colitis and Crohns disease.

Is scintigraphic double-track appearance a sign of severe acute episodes of ulcerative colitis?

AIM In comparison to endoscopy, clinical and biological criteria are less predictive of severity in attacks of ulcerative colitis (UC). Our aim was to assess the value of the double-track scintigraphic appearance in the assessment of the severity of acute UC by comparing it to endoscopic criteria. PATIENTS AND METHODS We reviewed medical records of 52 patients hospitalized for an acute attack of UC, who had undergone within 48 hours of presentation both a technetium 99m hexamethyl propylene amine oxime (99mTc-HMPAO) granulocyte scintigraphy and endoscopic examination (colonoscopy: n=20; rectosigmoidoscopy: n=32). RESULTS Taking into account the colonic segments examined together with both methods in the same patient or results obtained with colonoscopies, there was an excellent agreement between the double-track scintigraphic appearance and endoscopic criteria of severity. CONCLUSION In patients with previously diagnosed UC, 99mTc-HMPAO granulocyte scintigraphy when available may replace endoscopic examination to assess the severity of attacks.

L’allergie alimentaire et digestive chez l’adulte

n désigne sous le nom d’allergie alimentaire l’ensemble des manifestations cliniques qui surviennent lors de l’ingestion d’un aliment et qui sont déclenchées par une réaction immuno-allergique dirigée contre un allergène alimentaire [1]. Cette réaction fait suite à une sensibilisation préalable à l’allergène. Nous nous limiterons dans cette mise au point à l’allergie alimentaire de type IgE qui est la mieux documentée actuellement. Le terme d’allergie digestive est plus restrictif : il désigne les manifestations digestives secondaires à l’ingestion d’aliments et déclenchées également par une réaction immuno-allergique de type IgE [2]. À côté de l’allergie alimentaire, il existe des réactions adverses aux aliments qui ne sont pas déclenchées par une réaction immunologique. Ces réactions peuvent être d’origine toxique (par exemple ingestion d’amanite phalloïde) ou non et surviennent alors pour une raison métabolique (par exemple ingestion d’aliments riches en histamine) ou liée à un déficit enzymatique intestinal (par exemple intolérance à certains sucres). Épidémiologie

Rectocolite ulcéro-hémorragique chronique active: Efficacité de la ciclosporine intra-veineuse puis orale, associée à l’azathioprine

OBJECTIVE To know whether the therapeutic protocol applied in the case of severe acute ulcerative colitis (UC) associating ciclosporine and azathioprine was also effective in the case of moderate chronic active ulcerative colitis (UC). SUBJECTS AND METHODS in this retrospective study 10 patients (31-65 years, 6 distal colitis, 1 left colitis, 3 pancolitis) moderately active and corticosteroid-resistant or dependent were included. Patients received ciclosporine intraveinously (4 mg/kg/d) and were evaluated 10 days later. If efficient, ciclosporine was given orally for 3 Months, azathioprine was introduced and steroids were progressively tapered. RESULTS on inclusion the clinical score, based on the Mayo Clinic score, was of 5.7 +/- 0.5. On Day 10, the score decreased significantly (2.1 +/- 0.7, p<0.001) and the therapeutic effect was sustained at the third Month (1.8 +/- 0.7). With azathioprine, 4 patients were still in remission with a mean follow up of 23.3 +/- 15.5 Months. CONCLUSION therapeutic scheme proposed in severe acute UC failing to respond to steroids may be helpful in some patients with a chronic active UC. Clinical improvement is rapid and long-term response is maintained in about 1 patient out of 2.Resume Objectif Savoir si le protocole therapeutique applique en cas de rectocolite ulcero-hemorragique (RCH) severe associant la ciclosporine a l’azathioprine etait egalement efficace en cas de RCH moderee chronique active. Methode Dans cette etude prospective, 10 patients (31-65 ans, 6 colites distales, 1 colite gauche, 3 pancolites) en poussee moderee et cortico-resistants ou cortico-dependants depuis au moins 3 mois ont ete inclus. Ils ont ete traites par ciclosporine intra-veineuse (4 mg/kg/jour) et reevalues 10 jours plus tard. En cas d’efficacite, la ciclosporine etait prescrite per os , l’azathioprine introduite et la decroissance des corticoides debutee. La ciclosporine etait maintenue 3 mois avec relais par l’azathioprine. Resultats A l’inclusion le score clinique, evalue a partir des criteres de la Mayo Clinic , etait de 5,7 ± 0,5. Au 10 e jour, le score baissait significativement (2,1 ± 0,7 p e mois (score 1,8 ± 0,7). Sous azathioprine, 4 patients etaient toujours en remission avec un suivi moyen de 23,3 ± 15,5 mois. Conclusion Le protocole therapeutique applique en cas de colite grave de RCH peut etre une aide therapeutique chez certains malades ayant une forme chronique active de la maladie. L’amelioration clinique est rapide et se maintient a long terme chez environ 1 patient sur 2.

TNFα reduces in vitro butyrate oxidation in human colon: A link from inflammatory process to mucosal damage?

TNFa Reduces In Vitro Butyrate Oxidation In Human Colon: A Link From Inflammmatory Process To Mucosal Damage? Stephane Nancey, Dept of Gastroenterology, Lyon-Sud Hosp, Pierre-Benite France; Francoise Andre, Dept of Immunology, Lyon-Sud Hosp, Pierre-Benite France; Sylvette Claudel, Dept of Gastroenterology, Lyon-Sud Hosp, Pierre-Benite France; Claude Andre, Dept of Immunology, Lyon-Sud Hosp, Pierre-Benite France; Louis Descos, Bernard Flourie, Dept of Gastroenterology, Lyon-Sud Hosp, Pierre-Benite France