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J Fournet

Publications and source records attributed to J Fournet.

At least 19 recordsLinked to original sources

Randomised trial comparing three different schedules of infusional 5FU and raltitrexed alone as first-line therapy in metastatic colorectal cancer. Final results of the Fédération Francophone de Cancérologie Digestive (FFCD) 9601 trial.

LV5FU2 with high-dose leucovorin (LV), weekly infusional 5-fluorouracil (5FU) (AIO schedule) and raltitrexed have been demonstrated to be active agents in first-line treatment of colorectal cancer. We performed a 4-arm randomised trial to compare (1) a low-dose intravenous bolus of LV (20 mg/m2), followed by an intravenous bolus of 5FU (400 mg/m2), followed by a 22-hour continuous infusion of 5FU (600 mg/m2) on day 1 and day 2/2 weeks (ldLV5FU2 arm), (2) a weekly continuous infusion of high-dose 5FU (2.6 g/m2/week) for 6 weeks followed by a rest week (HD-FU arm) and (3) raltitrexed (Tomudex arm; 3 mg/m2/3 weeks) to standard LV5FU2. From 1997 to 2001, 294 patients were included. The 4 arms were well balanced for sex ratio, age, WHO performance status, the primary tumour site and prior adjuvant chemotherapy. Treatment was stopped due to low accrual. Two toxicity-related deaths were observed in the Tomudex arm. The treatments gave rise to different rates of grade 3-4 neutropenia (3, 4, 11 and 14% of the patients in the LV5FU2, ldLV5FU2, HD-FU and Tomudex arms, respectively, p = 0.028), leucopenia and vomiting. At least one episode of grade 3-4 toxicity was observed in 27, 25, 38 and 47% of the patients in the LV5FU2, ldLV5FU2, HD-FU and Tomudex arms, respectively (p = 0.016). An objective response was observed in 28, 21, 22 and 10% of the patients in the LV5FU2, ldLV5FU2, HD-FU and Tomudex arms, respectively (p = 0.04). Progression-free survival (PFS) of the patients in the Tomudex arm was statistically lower compared to that of patients treated with LV5FU2 or ldLV5FU2 (combined group; p = 0.013, log rank test). In conclusion, Tomudex is more toxic and yields shorter PFS than infusional 5FU. Despite the early closure of the study and the lack of power of the comparison, it seems that ldLV5FU2 could be considered as an active, easier and less expensive option for the treatment of metastatic colorectal cancer compared to classic LV5FU2 or weekly HD-FU.

Aged↗

Relationship between acid reflux episodes and gastroesophageal reflux symptoms is very inconstant.

In this prospective study 244 consecutive patients presenting with typical and chronic signs of gastroesophageal reflux were included. Conventional 24-hr esophageal pH monitoring was carried out to establish the symptom association probability, the concordance index, and the symptom sensitivity index. The symptom association probability could be calculated in 110 patients (45%). Two groups were identified: group 1 had normal duration of esophageal acid exposure; subgroup la (nonsignificant symptom association probability) included 39 patients (35.5%) and subgroup lb (significant symptom association probability) included 24 patients (21.8%); group 2 had abnormal duration of esophageal acid exposure; subgroup 2a (nonsignificant symptom association probability) included 21 patients (19.1%) and subgroup 2b (significant symptom association probability) included 26 patients (23.6%). In all, 56.6% of the patients presented typical symptoms of reflux not directly determined by one or repeated acid reflux episodes. The correlation between symptom association probability and the symptom sensitivity index allows for more accurate determination of esophageal acid sensitivity (subgroups lb and 2b).

Adolescent↗

Central processing of rectal pain in patients with irritable bowel syndrome: an fMRI study.

OBJECTIVES: In healthy subjects, the neural correlates of visceral pain bear much similarity with the correlates of somatic pain. In patients with irritable bowel syndrome, the central nervous system is believed to play a strong modulatory or etiological role in the pathophysiology of the disease. We hypothesize that this role must be reflected in aberrations of central functional responses to noxious visceral stimulation in these patients. To verify this hypothesis, we have induced transient rectal pain in patients and assessed the functional responses of the brain by means of functional magnetic resonance imaging. METHODS: Twelve right-handed patients (11 female) were examined. Functional imaging (1.5 T) was performed following a block paradigm, alternating epochs with and without noxious stimulation of the rectum. Rectal pain was induced by inflating a latex balloon. Whole-brain coverage was achieved by means of echo-planar magnetic resonance acquisition. RESULTS: A strong variability of the individual responses to rectal pain was found in patients with irritable bowel syndrome. Significant activations were found in only two patients, and group analysis did not reveal significant activations. In contrast, all patients exhibited significant deactivations. Group analysis revealed significant deactivations within the right insula, the right amygdala, and the right striatum. CONCLUSIONS: This study reveals aberrant functional responses to noxious rectal stimulation in patients with irritable bowel syndrome. Those results add grounds to the hypothesis that the central nervous system plays a significant role in the pathophysiology of this syndrome.

Adult↗

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.

Aged↗

Decreasing oesophageal acid exposure in patients with GERD: a comparison of rabeprazole and omeprazole.

BACKGROUND: Rabeprazole has been shown to be more potent and faster than other proton pump inhibitors in in vitro studies and highly effective in decreasing oesophageal acid exposure in patients with gastro-oesophageal reflux disease (GERD). AIM: This study was a multicentre, double-blind, placebo-controlled, randomized, parallel-group comparison of three active treatment regimens utilizing two different proton pump inhibitors, or placebo, administered over 7 days in patients with GERD. METHODS: Eighty-two patients with symptomatic GERD were given placebo, rabeprazole 10 mg b.d., rabeprazole 20 mg o.m., or omeprazole 20 mg o.m. for 7 days. Twenty-four hour oesophageal pH monitoring was performed at baseline and repeated at the conclusion of the treatment period. RESULTS: At the end of study, the percentage time (mean +/- s.d.) with pH < 4 over a 24-h period was significantly decreased by the three active regimens but without significant difference between them (9.27 +/- 4.77; 2.53 +/- 4.27; 2.02 +/- 1.71 and 2.91 +/- 4.06 for placebo, rabeprazole 10 mg b.d., rabeprazole 20 mg o.m. and omeprazole 20 mg o.m., respectively). Acid exposure was normalized in 90% of patients treated with rabeprazole 10 mg b.d., 95% treated with rabeprazole 20 mg o.m., 78% treated with omeprazole 20 mg o.m., and only 9.5% of patients treated with placebo. Both rabeprazole and omeprazole were well-tolerated. CONCLUSIONS: Although rabeprazole 20 mg o.m. showed greater activity numerically, this study demonstrates that rabeprazole 10 mg b.d. and 20 mg o.m. are equivalent to omeprazole 20 mg o.m. in decreasing oesophageal acid exposure.

2-Pyridinylmethylsulfinylbenzimidazoles↗

A malignant gastrointestinal stromal tumour in a patient with multiple endocrine neoplasia type 1.

Loss of heterozygosity for polymorphic markers flanking the multiple endocrine neoplasia type 1 (MEN-1) gene in parathyroid and pancreatic islet tumours from subjects with MEN-1 has been well documented and has led to the hypothesis that the MEN-1 gene functions as a recessive tumour suppressor gene. We report a case of MEN-1 with duodeno-pancreatic gastrinoma, parathyroid hyperplasia, pituitary adenoma, adrenal adenoma, and lipomas, whose rare association with a malignant gastrointestinal stromal tumour (GIST) represents an undescribed combination. MEN-1 mutation in this family was shown as a frameshift (1607delA) in exon 10. To assess the role of the MEN-1 gene in the pathogenesis of tumours less commonly associated with MEN-1, we studied GIST DNA for loss of the unaffected MEN-1 gene allele. Stromal tumour and peripheral leucocyte DNAs from our patient were examined for loss of heterozygosity using the PYGM microsatellite polymorphism and an intragenic polymorphism (D418D in exon 9) in the MEN-1 gene. We showed no evidence for loss of the wild-type MEN-1 allele in GIST. The MEN-1 germline inactivating mutation 1607delA-ter558 in exon 10 was detected in the stromal tumour DNA, but no somatic mutation in the wild-type MEN-1 allele in GIST DNA was detected. Occurrence of GIST could be consistent with the possibility that this MEN-1-related uncommon neoplasm arose independently by a mechanism unrelated to the MEN-1 gene.

Adult↗

Fedotozine, a kappa-opioid agonist, prevents spinal and supra-spinal Fos expression induced by a noxious visceral stimulus in the rat.

Fedotozine, a kappa opioid agonist, reverses digestive ileus caused by acetic acid (AA)-induced visceral pain in rats. The aims of this study were: to map, in conscious rats, central pathways activated by AA using Fos as a marker of neuronal activation; to characterize primary afferent fibres involved in this activation; and to investigate the effect of fedotozine on AA-induced Fos expression. AA (0.6%; 10 mL kg-1) was injected i.p. in conscious rats either untreated; pretreated 14 days before with capsaicin; pretreated 20 min previously with fedotozine; or pretreated 2 h prior to fedotozine with the kappa-antagonist nor-binaltorphimine (nor-BNI). Controls received the vehicle alone. 60 min after injection of AA, rats were processed for Fos immunohistochemistry. Visceral pain was assessed by counting abdominal cramps. AA induced Fos in the thoraco-lumbar spinal cord (laminae I, V, VII and X) and numerous brain structures such as the nucleus tractus solitarius, and paraventricular nucleus (PVN) of the hypothalamus, whereas almost no Fos labelling was observed in controls. Capsaicin pretreatment blocked AA-induced Fos in all structures tested. Fedotozine significantly decreased AA-induced abdominal cramps and Fos immunoreactivity in the spinal cord and PVN, this effect being reversed by nor-BNI pretreatment. AA induces Fos in the spinal cord and numerous brain nucuei, some of which are involved in the control of digestive motility in rats. This effect is mediated through capsaicin-sensitive afferent fibres and prevented by fedotozine most likely through a peripheral action on visceral afferents.

Abdominal Pain↗

[Is argon plasma coagulation an efficient treatment for digestive system vascular malformation and radiation proctitis?].

BACKGROUND AND AIMS: Argon beam coagulation is an innovative no-touch electrocoagulation technique in which high-frequency monopolar alternating current is delivered to the tissue through ionized argon gas. The aim of this prospective study was to evaluate the efficacy and safety of argon plasma coagulation (APC) for the treatment of hemorrhagic digestive vascular malformations and hemorrhagic radiation proctosigmoiditis. METHODS AND PATIENTS: From March 1998 through April 1999, we used endoscopic APC (ERBE, Lyon, France, argon gas source ICC 300, high-frequency electrosurgical generator ICC 200, gas flow 1 L/min, power setting 50 W) to treat 39 consecutive patients (mean age 70.3 +/- 10 years). The indications for treatment were anemia (n =10), active or oozing haemorrhage (n =15) from digestive angiodysplastic lesions (n =25), hemorrhagic antral telangiectatic vascular lesions (n =2), and hemorrhagic radiation proctosigmoiditis (n =12) after failure of medical treatments (5-aminosalicylic acid, corticosteroids, or sucralfate enemas). The efficacy of APC treatment was evaluated on symptoms, transfusion requirement, bleeding recurrence, hemoglobin value before and 6 months after APC therapy. RESULTS: On the average, 1 +/- 0.5 sessions per patient was required to treat digestive vascular malformations. Definitive haemostasis of digestive angiodysplastic lesions with active or oozing haemorrhage was achieved in one session in all patients. No bleeding recurrence was observed during the follow-up period of 6 months. Anemia recurrence was observed in 2 patients (7%). Average hemoglobin levels recorded before and 6 months after APC therapy were 78.8 +/- 21.2 g/L and 108 +/- 13.7 g/L, respectively (P<0.05). On the average, 2.8 +/- 0.8 sessions per patient were required to treat hemorrhagic radiation proctosigmoiditis. Ten patients (83%) reported improvement or cessation of rectal bleeding, most of them immediately after APC therapy. Endoscopic control was performed one month after APC therapy and showed complete disappearance of lesions in 8 patients (66%). Average hemoglobin levels recorded before and 6 months after APC therapy were of 102.7 +/- 21 g/L and 120 +/- 19.5 g/L, respectively (P <0.05). Complications were observed in 5 cases (13%): pneumoperitoneum in 2 cases, chronic rectal ulcerations in 2 cases, and nonsymptomatic rectal stenosis in 1 case. CONCLUSION: APC appears to be a simple, safe, and effective technique in the management of hemorrhagic radiation-induced proctosigmoiditis and hemorrhagic lesions.

Adult↗

[Evaluation of esophageal motility disorders triggered by ingestion of solids in the case of non-obstructive dysphagia].

UNLABELLED: The aim of this study was to define the normal manometric pattern of esophageal motility in response to food ingestion and to evaluate the contribution of esophageal manometry in the management of patients complaining of functional dysphagia. PATIENTS AND METHODS: Twenty-one healthy volunteers and 25 consecutive patients complaining of functional dysphagia with normal conventional esophageal manometry were included in this prospective study. An event marker was used to study the relationship between dysphagia and motility events. RESULTS: Twenty-two out of 25 patients (88%) reported dysphagia during esophageal manometry with food ingestion, while none complained of dysphagia during conventional esophageal manometry. Significantly, food ingestion induced in healthy volunteers and in patients: an increase in the amplitude and duration of esophageal body peristaltic contractions, and a decrease in their propagation speed; an increase in the basal pressure and a decrease in the relaxation percentage of the lower esophageal sphincter during deglutition. The percentage of solid swallows with one or several of the 7 abnormal motility patterns studied prospectively was significantly higher among patients (53.7%) than among healthy volunteers (4.3%) (P < 0.0001); it was also significantly higher among patients during swallows with dysphagia (70.1%) than without dysphagia (33.6%) (P < 0.0001). CONCLUSION: Esophageal manometry with food ingestion is an effective means of defining abnormal motility patterns and their relationship with dysphagia during functional dysphagia.

Adult↗

[Are self-expanding metallic esophageal prostheses an effective treatment for malignant stenosis of the esophagus? A prospective study of 32 cases].

UNLABELLED: The treatment of esophageal carcinoma is frequently palliative. The aims of this prospective study were to evaluate the functional results of covered self expanding esophageal metal stents in patients with malignant obstruction of the esophagus and to compare two models of stent. PATIENTS AND METHODS: From April 1994 to August 1996, 32 patients were treated with 35 metal stents (Cook Z Stent Wilson Cook: n = 21; Ultraflex Boston Scientific: n = 14). Ten patients had a fistula. Previous treatment was effective in 30 patients. Initial score of dysphagia was 2.68 +/- 0.7. Initial score of Karnofsky was 60 +/- 10%. The metal stents could be placed in 100% of cases. The 30-day mortality was 0%. The morbidity of device placement of metal stents was 28%. The treatment of fistulas was effective without complication in 100% of cases. At month 3, we observed a significant decrease of dysphagia score (0.43 +/- 0.25) and a significant increase of Karnofsky score (75 +/- 10%) (P < 0.001). The mean duration of hospitalization was 5.4 +/- 1.3 days. During mean follow-up of 18 +/- 3.5 months, 14 patients (44%) died. Any difference concerning mortality and functional results was observed between 2 kinds of metal stents. We only observed a significant decrease of retrosternal pain in patients treated with Ultraflex prothesis. CONCLUSION: Self-expanding esophageal metal stents are a simple and effective palliative treatment of malignant obstruction of the esophagus. However, their high cost need other cost-efficacy studies to define their indications.

Aged↗