Adjuvant gemcitabine and concurrent radiation for patients with resected pancreatic cancer: a phase II study.

The safety and efficacy of gemcitabine and concurrent radiation to the upper abdomen followed by weekly gemcitabine in patients with resected pancreatic cancer was determined. Patients with resected adenocarcinoma of the pancreas were treated with intravenous gemcitabine administered twice-weekly (40 mg m(-2)) for 5 weeks concurrent with upper abdominal radiation (50.4 Gy in 5(1/2) weeks). At the completion of the chemoradiation, patients without disease progression were given gemcitabine (1000 mg m(-2)) weekly for two cycles. Each cycle consisted of 3 weeks of treatment followed by 1 week without treatment. Forty-seven patients were entered, 46 of whom are included in this analysis. Characteristics: median age 61 years (range 35-79); 24 females (58%); 73% stage T3/T4; and 70% lymph node positive. Grade III/IV gastrointestinal or haematologic toxicities were infrequent. The median survival was 18.3 months, while the median time to disease recurrence was 10.3 months. Twenty-four percent of patients were alive at 3 years. Only six of 34 patients with progression experienced local regional relapse as a component of the first site of failure. These results confirm the feasibility of delivering adjuvant concurrent gemcitabine and radiation to the upper abdomen. This strategy produced good local regional tumour control.

Small bowel length in Crohn's disease.

BACKGROUND AND AIMS: This prospective study compared jejunoileal length in patients with Crohn's disease (CD) and the general population to determine whether this parameter can be related to outcome and management of CD complications. PATIENTS AND METHODS: Small bowel (SB) length was measured during abdominal surgery prior to bowel resection in 93 patients with CD and 92 patients without inflammatory or small bowel disease. RESULTS: SB length was shown to be shorter in patients with CD (462 vs. 567 cm) and was correlated to sex and height. There was no correlation of SB length to clinical expression (perforating or nonperforating), site, or outcome. SB length is not a prognosis factor of postoperative relapse. The presence of perineal disease and systemic abnormalities seem to be the only prognostic factors of surgical recurrence. Sex, age at onset, time of first surgery, site of disease, and mode of onset are not predictive of surgical recurrence. CONCLUSION: We recommend minimal intestinal resection when surgical treating CD complications in patients at high risk of surgical relapse and initial short SB. We advise using stricturoplasty or leaving asymptomatic intestinal lesions to reduce short bowel syndrome occurrence when performing iterative surgery.

[Granulomatous arteritis through sarcoidosis]. / Antrite granulomateuse par sarcoïdose.

INTRODUCTION: Digestive localisation of sarcoidosis is rare. OBSERVATION: A 35 year-old man presented with sarcoidosis revealed by a mediastinal hilum lymphadenopathy 13 years earlier. Epigastric pain led to oeso-gastroduodenal fibroscopy and biopsies, showing inflammatory mucosa and numerous giant-cell epithelioid granulomas, without concomitant necrosis or fibrosis. COMMENTS: The clinical manifestations and endoscopic profile of gastric localisations of sarcoidosis are not specific. Diagnosis relies on several elements: presence of epithelioid granulomas without necrosis, history of sarcoidosis or the simultaneous existence of other localisations, evocative biological signs and the absence of elements evoking any other diagnosis. Treatment relies on corticosteroid therapy and sometimes requires endoscopic or surgical management.

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.

Therapeutic advances in the management of metastatic colorectal cancer.

Metastatic colorectal cancer has long been considered as a short-term, poor prognosis, chemoresistant disease. Until the early 1990s, the impact of systemic chemotherapy on patient outcome was debated. Recently, the emergence of new therapeutic modalities (5-FU modulations and associations with oxaliplatin and irinotecan) has led to a significant improvement in tumor response rates and patient survival. Thus, the indications of curative surgery of visceral metastases, frequently preceded and followed by chemotherapy, systemic or intra-arterial or both, have become more frequent. In this paper we will review and comment on the results of the major clinical trials published in the past 5 years and propose some decision strategies regarding the main clinical situations met in daily practice.

Prevalence of germline mutations of hMLH1, hMSH2, hPMS1, hPMS2, and hMSH6 genes in 75 French kindreds with nonpolyposis colorectal cancer.

Hereditary nonpolyposis colorectal cancer (HNPCC) is a syndrome characterized by familial predisposition to colorectal carcinoma and extracolonic cancers of the gastrointestinal, urological, and female reproductive tracts. This dominant disorder is caused by germline defects in one of at least five DNA mismatch repair (MMR) genes: hMLH1, hMSH2, hPMS1, hPMS2, and hMSH6 (GTBP). Germline mutations of hMSH2 and hMLH1 are also frequently identified in families not fulfilling all the Amsterdam criteria, thereby demonstrating that the involvement of these genes is not confined to typical HNPCC. To evaluate the respective involvement of the various MMR genes in typical and incomplete HNPCC syndromes, we have performed an analysis of the hMLH1, hMSH2, hPMS1, hPMS2, and hMSH6 genes in a large series of French kindreds (n=75) with colorectal tumors and/or aggregation of extracolonic cancers belonging to the HNPCC spectrum. Mutational analysis has been performed in all families, without preselection for the tumor phenotype. We have detected 26 pathogenic germline mutations of the hMLH1 and hMSH2 genes and several novel variants of the hPMS1, hPMS2, and hMSH6 genes. Our data confirm that, regardless of the type of families and the tumor phenotype, hPMS1, hPMS2, and hMSH6 germline mutations are rare in familial aggregation of colorectal cancers. Furthermore, they suggest that the presence of multiple primary malignancies in a single individual and the observation of extracolonic tumors in relatives of a colorectal cancer patient should be included among the guidelines for referring patients for genetic testing.

[A 1993-1995 epidemiological survey of home parenteral nutrition in approved centers for adults in France]. / Données épidémiologiques 1993-1995 de la nutrition parentérale à domicile en centres agréés chez l'adulte en France.

OBJECTIVES: A 1993-1995 three year epidemiological survey of home parenteral nutrition was performed through in France in approved centers for adults. METHODS: Data were retrospectively collected each year on a standardized questionnaire focussing on indications and short term outcome. RESULTS: All centers (n = 14) participated in the study and 524 new adult patients were recruited. The overall incidence was unchanged at 3.75 patients/10(6) adults. Indications for AIDS rose (8 to 18%) whereas other indications were stable. Prevalence increased by 19%: 4.40 adults/10(6) patients at 01.01.1996. At six months, the probability to stay on treatment was 19.5% for AIDS and cancer indications but 52% for others, whereas death rates were 59% and 9% respectively. CONCLUSIONS: For both cancer and AIDS indications, short-term treatment was due to a poor prognosis. For other diagnosis, complicated with a short bowel in 51% of cases, prognosis was excellent but associated with treatment dependency. The latter point focuses on the need for additional treatments in irreversible intestinal failure.

[Adjuvant treatment of colonic cancers]. / Traitement adjuvant des cancers coliques.

In the last decade, adjuvant chemotherapy has led to significant improvement in survival for large bowel cancer patients. The association of 5-FU plus levamisole was the first described and demonstrated its efficacy in stage Dukes C (T1,2,3,4 N1 M0) completely-resected adenocarcinoma. Recently, chemotherapy with 5-FU and folinic acid was recommended on the basis of randomized trials. Advances in adjuvant chemotherapy may result in increasing 5-FU doses as described in metastatic colorectal carcinomas, and in use of new drugs such as oxaliplatin or raltitrexed, whose activity has been well-studied in Dukes D (M1) carcinomas. Immunotherapy, intraperitoneal and intraportal infusion of chemotherapy are promising approaches but still in evaluation. The main difficulty for the future is to define the best therapeutic regimen in order to reach the highest improvement in survival.

[Type I hypersensitivity reactions and etiopathogenesis of hemorrhagic rectocolitis]. / Réactions d'hypersensibilité de type I et étiopathogénie de la rectocolite hémorragique.

There is a body of clinical, epidemiological, biologic, histological and therapeutic data suggesting that type I hypersensitivity plays a role in the pathogenesis and maintenance of ulcerative colitis. Contradictory evidence from different studies on the pathogenic mechanisms may simply mean that there is not one but several types of ulcerative colitis. Chronic inflammation of the intestine would cover a heterogeneous group of conditions. Genetic susceptibility controlling one of more anomalies of the immune system would be triggered by external factors such as respiratory or food allergies, viral or bacterial infections or other factors including smoking or stress. The wide range of factors involved would explain the variety of findings reported by different groups searching for a single pathogenic mechanism. Finally, as emphasized by other authors, screening for subgroups of patients with allergy among the ulcerative colitis population would be useful in adapting treatment and developing a more specific therapeutic strategy not only for acute phases but perhaps also for preventive treatment.

[Maintenance treatment of Crohn's disease using orally administered mesalazine (Pentasa). A controlled multicenter study. The Study Groups on the Treatment of Inflammatory Digestive Disorders]. / Traitement d'entretien de la maladie de Crohn par la mésalazine par voie orale (Pentasa). Etude contrôlée multicentrique. Groupe d'Etudes thérapeutiques des affections inflammatoires digestives (GETAID).

BACKGROUND: Mesalamine provides a new therapeutic approach in treating Crohn's disease. METHODS: To assess the efficacy and safety of slow-release mesalamine (Pentasa) in maintaining remission in Crohn's disease, 161 patients with inactive disease were randomized to receive either Pentasa (2 g/day) or placebo in a 2-year double-blind, multicenter trial. Two strata were defined according to the duration of their remission: < 3 months (n = 64) or 3-24 months (n = 97), presumed to be high and low relapse risk strata, respectively. RESULTS: The probability of relapse was higher in the short-remission placebo group than in the three other groups (p < 0.003), showing there was a significant benefit from Pentasa in the high relapse risk stratum. In this stratum, the 2-year on-going remission rate was of 29% +/- 9% and 45% +/- 11% (mean +/- SD) in the placebo and Pentasa groups, respectively. The incidences of side effects were similar in both groups. CONCLUSION: Pentasa (2 g/day for 2 years) is a safe and effective maintenance treatment for Crohn's disease when given within 3 months of achieving remission.

Outcome of perianal fistulae in Crohn's disease--value of Hughes' pathogenic classification.

Applying the Hughes' pathogenic classification of ano-perineal lesions of Crohn's disease, this study was conducted to find out its possible prognostic value in perianal fistulas. Thirty-eight patients with ano-perianal fistulas were included; primary specific lesions (condyloma, cavitating ulcer, fissure) were found in 22 patients (group 1) and were absent in the other 16 patients (group 2). Patients of group 1 underwent more abdominal surgical interventions (G 1: 68%; G 2: 31% - P = 0.05), as well as proctological interventions (G 1: 2.95 operations/patient vs 1.35 in G 2 - P = 0.01). Perfect continence was recorded ultimately in 31.8% patients of G 1 compared to 62.5% of G 2. This study shows the very poor prognosis of ano-perianal fistulas in Crohn's disease.

Oral mesalamine (Pentasa) as maintenance treatment in Crohn's disease: a multicenter placebo-controlled study. The Groupe d'Etudes Thérapeutiques des Affections Inflammatoires Digestives (GETAID)

BACKGROUND: Mesalamine provides a new therapeutic approach in treating Crohn's disease. METHODS: To assess the efficacy and safety of slow-release mesalamine (Pentasa; Ferring AS, Vanløse, Denmark) in maintaining remission in Crohn's disease, 161 patients with inactive disease were randomized to receive either Pentasa (2 g/day) or placebo in a 2-year double-blind, multicenter trial. Two strata were defined according to the duration of their remission: < 3 months (n = 64) or 3-24 months (n = 97), presumed to be high and a low relapse risk strata, respectively. RESULTS: The probability of relapse was higher in the short-remission placebo group than in the three other groups (P < 0.003), showing there was a significant benefit from Pentasa in the high relapse risk stratum. In this stratum, the 2-year ongoing remission rate was of 29% +/- 9% and 45% +/- 11% (mean +/- SD) in the placebo and Pentasa groups, respectively. The incidences of side effects were similar in both groups. CONCLUSIONS: Pentasa (2 g/day for 2 years) is a safe and effective maintenance treatment for Crohn's disease when given within 3 months of achieving remission.

[Ileocolitis caused by Herpes simplex virus type 2]. / Iléo-colite herpétique à virus Herpes simplex de type 2.

The authors report the case of a 51-year-old woman who was hospitalized for severe acute colitis. Sub-total colectomy was performed, due to clinical deterioration and resistance to treatment. The examination of the surgery specimen revealed a herpes-virus type 2 as the responsible pathogen agent. Complementary aciclovir treatment cured the patient.