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Biomedical subjects

E Dorval

Publications and source records attributed to E Dorval.

17 recordsLinked to original sources

Different segmental transit times in patients with irritable bowel syndrome and "normal" colonic transit time: is there a correlation with symptoms?

BACKGROUND: The Rome criteria serve as gold standard for establishing a diagnosis of irritable bowel syndrome (IBS), but only represent a cluster of symptoms. On the other hand, measurement of colonic transit time (CTT) with radiopaque markers is a solid and more objective method to quantify functional abnormalities. The goal of this study was to investigate whether the IBS symptoms, as defined in the Rome II criteria, correspond to objective physiological parameters, i.e. CCTs. METHODS: The study enrolled 148 healthy control subjects and 1385 consecutive IBS patients. Transit times were measured for the whole rectocolon (overall CTT) and for 3 segments (right colon, left colon, rectosigmoid area); segmental distribution of markers and diffusion coefficients were also assessed. In order to analyze homogeneous groups, we restricted analysis to subjects with "normal" CTT (< or =70 hours). RESULTS: Six hundred forty four IBS patients (46%) and 14 control subjects (9%) had CTT >70 h and were eliminated. In subjects with CTT < or =70 h, CTT did not follow a normal (Gaussian) distribution. We identified 3 different CTT clusters in healthy controls and 4 clusters in IBS patients. Even if CTT was not significantly different between clusters, each cluster was characterized by a specific pattern of segmental colonic transit. There was a marked gender difference: women had longer overall CTT values than men, both in control and IBS patient groups (p<0.001). However, female IBS patients had significantly shorter colorectal transit times than female controls (p<0.001), as well as faster transit than in men through the left colon and rectosigmoid area. There were no significant differences in transit time between male IBS patients and male controls with the exception of a faster rectal transit in IBS patients (p<0.01). There was no association between segmental colonic transit values and sign or symptoms comprising the Rome II criteria. CONCLUSIONS: In subjects with CTT < or =70 h, CTT does not follow a normal distribution but is clustered in subgroups that can be distinguished only by measuring segmental colonic transit. Within these subgroups, there is a marked difference in transit times between IBS patients and normal subjects, suggesting that IBS patients with "normal" CTT are not "normal". The Rome II criteria do not reflect differences in segmental transit times in IBS patients with "normal" CTT. We therefore propose to evaluate segmental transit times in IBS patients with "normal" CTT, before and after treatment, in order to correctly interpretate variations in signs and symptoms. These findings have important implications in evaluating the effect of drugs on bowel function and should help define better inclusion criteria for studies evaluating new drugs for the treatment of IBS.

Adolescent↗

'A phase II study of oral uracil/ftorafur (UFT) plus leucovorin combined with oxaliplatin (TEGAFOX) as first-line treatment in patients with metastatic colorectal cancer'.

This phase II trial was performed to evaluate the efficacy and tolerability of a new combination of Uracil/Ftorafur (UFT)/leucovorin (LV) and oxaliplatin in patients (pts) with metastatic colorectal cancer (MCRC) who had not received prior chemotherapy for metastatic disease. Between February 2002 and October 2002, 64 patients received UFT 300 mg m(-2) day(-1) and LV 90 mg day(-1) from day 1 to day 14 combined with oxaliplatin 130 mg m(-2) on day 1, every 3 weeks. All patients were evaluable for safety analysis and 58 of 64 patients were eligible for efficacy. Responses were reviewed by an independent review committee. Of the 58 per-protocol defined assessable patients, 1 complete response and 20 partial responses were observed yielding a response rate of 34% (95% CI: 22-47). The median response duration was 8.74 months (range 1.6-14). The median time to progression and the median survival were 5.88 months (95% CI: 4.34-8.21) and 18.2 months (95% CI: 10-20.7), respectively. Diarrhoea and peripheral neuropathy were the most frequent and predictable toxicities. These events were reversible, noncumulative and manageable. Grade 3 diarrhoea occurred in only 11% of the patients. No grade 4 gastrointestinal toxicity was reported in the study. The incidence of grade 3/4 (National Cancer Institute Common Toxicity Criteria 2: NCI-CTC 2) peripheral neuropathy was 15%. Haematological toxicity was of mild to moderate intensity with 10% of the patients with Grade 3/4 neutropenia without any episode of complication. The TEGAFOX regimen, a new combination using UFT/LV and oxaliplatin every 3 weeks is feasible on an outpatient basis. The combination is safe and active and may offer a promising alternative to the intravenous route. Nevertheless this efficacy results should be confirmed by randomized phase III trials.

Administration, Oral↗

A phase II trial of raltitrexed (Tomudex) in advanced pancreatic and biliary carcinoma.

PURPOSE: To evaluate the impact of raltitrexed (Tomudex) on the quality of life in a multicenter, phase II study in advanced pancreatic and biliary carcinomas. PATIENTS AND METHODS: Forty-six patients with advanced, histologically proven pancreatic (n = 37, 80.4%) or biliary (n = 9, 19.6%) carcinoma received 3 mg/m2 raltitrexed intravenously once every 3 weeks. For the quality of life assessments, EORTC QLQ-C30 was used, and the evaluation of the clinical benefit was performed according to the 4 criteria of the clinical benefit response. All patients were assessed for safety, and 41 patients were evaluable for objective response. RESULTS: Patients (63% male/37% female) had a mean age of 61.2 years, 71.7% had a PS of 0-1, 78.3% had metastatic disease, and 63% had at least 2 tumoral sites. A total of 176 cycles were administered with a mean of 4 cycles per patient (range 1-12). Three out of 43 patients evaluable for EORTC QLQ-C30 (7.0%; CI(95%) 1.4-19.0%) had a quality of life improvement. Thirty-two patients fulfilled the 4 criteria required to evaluate the clinical benefit response; 5 were responders (15.6%; CI(95%) 5.3-32.8%); 1 patient was a good responder based on both the EORTC questionnaire and the clinical benefit response. Forty-one patients were assessable for response, 3 responded to treatment (response rate: 6.5 %; CI(95%) 1.3-17.9%). Median survival was 4.6 months (CI(95%) 2.9-8.2 months), the 1-year survival rate was 21.8%. The most common grade 3-4 toxicities were neutropenia (8%), leukopenia (8%), thrombopenia (6%), anemia (6%), liver enzyme elevations (11%), asthenia (9%), vomiting (9%), abdominal pain (7%), and phlebitis (6%). One treatment-related death occurred (neutropenic sepsis). CONCLUSION: Raltitrexed appeared to be generally well tolerated and showed a clinical benefit response and/or quality of life improvement in a limited number of patients.

Antimetabolites, Antineoplastic↗

[Morbidity and mortality of acute pancreatitis. Prospective study in a French university hospital].

OBJECTIVE: According to certain learned societies, acute pancreatitis mortality should not exceed 10%. The aim of our work was to review the etiology, severity and mortality of acute pancreatitis in a prospective series of patients admitted to a regional university hospital in France, using standardised collection of data assessing the medico-surgical habits in the management of acute pancreatitis. METHODS: From February to September 1999, 86 patients (54 men and 32 women with a mean age of 58.5 years) were admitted for 88 episodes of acute pancreatitis. Data was collected from all the patients on admission and permitted measurement of the severity and prognosis scores and the study of the etiology, complications and management of the latter and the mortality with acute pancreatitis. RESULTS: Ranson's score was a mean of 2.4. Balthazar's score was superior or equal to D in 45% of cases. The respective prevalence of lithiasis, alcoholism, tumors, others or undetermined was of 41%, 37.5%, 7%, 5.5% and 9%. Acute pancreatitis was severe (multi organ failure, pseudo-cyst, systemic or necrotic infection and occlusive syndrome) in 32% of cases. Complications were: infection (22%), pseudo-cyst (14%), pleural effusion (12.5%) and occlusive syndrome (3.5%). Fever of more than 38.5 degrees C was noted in more than half of the patients. The median duration of hospitalisation was of 11 days (range: 1-86 days). Global hospital mortality was of 13.6% (12/88), and of 43% (12/28) in cases of severe acute pancreatitis. Six deaths occurred within the first 8 days of acute pancreatitis, and 6 after 8 days. Seven deaths (59%) were due to multi organ failure, 4 (33%) to infectious causes and one to another cause. CONCLUSION: The standardized collection of clinical and progressive data used in this study permitted assessment of the medico-surgical habits in a regional university hospital.

Acute Disease↗

The value of immunoscintigraphy in the detection of recurrent colorectal cancer.

The aim of this prospective study was to determine whether anti-carcinoembryonic antigen (anti-CEA) scintigraphy is a useful additional technique in the diagnosis recurrence of colorectal cancer. Forty patients with suspected recurrence of colorectal cancer, underwent immunoscintigraphy (IS) and helical computed tomography (CT) in the 2 weeks before surgery. Surgical findings were used to evaluate the performance of the imaging techniques. Suspected areas on IS and CT were systematically explored. Helical CT was found to be superior to IS for the liver, the sensitivity and specificity of CT being 100% and 90%, respectively, vs 53% and 100% for IS. However, IS was better than CT for the detection of extra-hepatic abdominal recurrence: sensitivity and specificity of IS were 100 and 82% respectively vs 33 and 82% for CT. Seven cases of peritoneal carcinomatosis were overlooked by helical CT. Our results indicate that IS improves detection of extra-hepatic abdominal recurrence of colorectal cancer. Immunoscintigraphy is valuable as a guide to the treatment strategy and operative procedures.

Adenocarcinoma↗

A new cyclooxygenase-2 inhibitor, rofecoxib (VIOXX), did not alter the antiplatelet effects of low-dose aspirin in healthy volunteers.

The present study examined whether rofecoxib (VIOXX), a new specific inhibitor of cyclooxygenase-2 (COX-2), would interfere with the desired antiplatelet effects of aspirin. Thus, the effects of rofecoxib on inhibition of ex vivo serum-generated thromboxane B2 (TXB2) and platelet aggregation by low doses (81 mg) of aspirin were examined in healthy volunteers. This was a double-blind, randomized, placebo-controlled, parallel study of two treatment groups (n = 12 per group) in which subjects received 50 mg of rofecoxib or placebo for 10 days in a blinded fashion. Subjects also received 81 mg aspirin once on each of days 4 through 10 in an open-label fashion. Blood for measurement of serum TXB2 production and platelet aggregation studies was collected on day 1 (prior to rofecoxib/placebo), on day 4 (prior to aspirin), and on day 10 (before and 4 hours following the seventh dose of aspirin). Platelet-derived serum TXB2 (COX-1 assay) was measured in blood clotted for 1 hour at 37 degrees C. Platelet aggregation was independently induced employing 1 mM arachidonic acid and 1 microgram/mL collagen as agonists. Rofecoxib administered alone had no significant effect on serum TXB2 production or platelet aggregation (day 4). TXB2 production was inhibited 98.4% by aspirin coadministered with either rofecoxib or placebo (day 10). Similarly, platelet aggregation induced by arachidonic acid was inhibited 93.7% and 93.5% by aspirin coadministered with either rofecoxib or placebo, respectively (day 10). The comparable values for inhibition of collagen-induced platelet aggregation were 86.8% and 90.8%, respectively. No important clinical or laboratory adverse experiences were observed. In conclusion, rofecoxib alone (50 mg QD for 4 days) did not inhibit serum TXB2 production or platelet aggregation. In addition, rofecoxib (50 mg QD for 10 days) did not alter the antiplatelet effects of low-dose aspirin (inhibition of platelet aggregation and TXB2 production). Rofecoxib was generally well tolerated when administered alone or in combination with low-dose aspirin.

Adolescent↗

Radiotherapy with high dose rate brachytherapy boost and concomitant chemotherapy for Stages IIB and III esophageal carcinoma: results of a pilot study.

PURPOSE: Radiotherapy (RT) and concomitant chemotherapy (CT) is the standard treatment for non resectable esophageal cancer. Usual total radiation dose is 50 Gy. In order to enhance local control rate a Phase II study was initiated to evaluate the feasibility of a combined treatment with an external radiation dose of 60 Gy and three cycles of concomitant CT, using the three main active drugs (CDDP, 5 FU and MMC), followed by a high dose rate (HDR) brachytherapy delivering 10 Gy. METHODS AND MATERIALS: Fifty-three patients, 48 men and 5 women, were entered in this study. Stages were evaluated with CT scan and with endoscopic sonography. Fifteen were Stage IIB, 38 Stage III. Treatment consisted of conventional fractionated RT to a total dose of 60 Gy delivered with 2 Gy per fraction, one fraction per day and five fractions per week. The CT regimen was a combination of Cisplatinum (CDDP) 20 mg/m2 and 5 Fluorouracil (5FU) 600 mg/m2 continuous infusion, from days 1-4 Mitomycin C (MMC) was given at 6 mg/m2 on day 1. Three cycles were administered on days 1, 22, and 43. Brachytherapy was delivered one week after the end of external radiation therapy. RESULTS: Full radiation therapy dose was delivered for 94% of the patients. CT compliance, evaluated on the mean relative dose-intensity was 85% for CDDP, 81% for 5FU and 51% for MMC. Overall grade 3 and 4 WHO toxicity rates were 23% and 7%, respectively. Haematologic toxicity was the most limiting factor. One patient died from treatment toxicity. Local control rate at one year was 74%. Three-year actuarial survival rate was 27%. Distant metastasis was the main cause of treatment failure. Swallowing score was good for 75% of the patients. Stage, performance status and weight loss were prognostic factors. CONCLUSION: This regimen with high dose RT, HDR brachytherapy and concomitant CT is feasible; however, a high level of haematologic toxicity was observed with the CDDP, 5FU and MMC regimen. Despite a poor compliance with CT, treatment results are very encouraging for patients with locally advanced disease.

Adult↗

Preoperative radiotherapy (RT) for rectal cancer: predictive factors of tumor downstaging and residual tumor cell density (RTCD): prognostic implications.

PURPOSE: To determine predictive factors and prognostic value of tumor downstaging and tumor sterilization after preoperative RT for rectal cancer. METHODS AND MATERIALS: Between 1977 and 1994, 167 patients with a histologically proven adenocarcinoma (70 T2, 65 T3, 29 T4, and 3 local recurrences) underwent preoperative RT. Median dose was 44 Gy (5-73 Gy). Surgery was performed in a mean time of 5 weeks after RT. Pathologic specimens have been reviewed by the same pathologist in order to specify the modified Astler Coller classification (MAC), and to quantify the residual tumor cell density (RTCD). RESULTS: According to the MAC, there was 9 stage 0 (5%), 10 stage A (6%), 103 stage B1-B3 (62%), and 45 stage C1-C3 (27%) tumors. Seventeen percent and 56% of the patients who received a dose > or = 44 Gy had respectively a 0-A and a B tumor, compared to 4 and 69% in those who received a dose < 44 Gy (p = 0.04). Tumor differentiation and a longer interval before surgery were significantly associated with a more frequent downstaging, and preoperative staging correlated well to the postoperative pathological findings. According to the RTCD, 62 tumors (37%) showed no or only rare foci of residual tumor cells (Group 1); 62 (37%) showed an intermediate RTCD (Group 2); and 43 (26%) a high RTCD (Group 3). No predictive factor of RTCD was statistically significant. In univariate analysis, postoperative staging was a significant prognostic factor, with corresponding 5-year overall survival rates in 0-A, B, and C stages of 92, 67, and 26% (p < 0.01). RTCD was not a prognostic factor. However, overall and disease-free survival rates for patients with complete pathologic response of 83% at 2 and 5 years suggested a better outcome in this subgroup of patients. CONCLUSION: The favorable influence of higher doses of preoperative RT on pathologic stage has been observed. Tumor differentiation, preoperative classification and time before surgery were the other predictive factors of tumor downstaging. However, there was no predictive factor of complete pathologic response. Even after preoperative RT, postoperative staging remained a prognostic factor.

Adenocarcinoma↗

[Effect radiotherapy on postoperative staging and residual tumor cell density in rectal cancers].

PURPOSE: To determine predictive factors and prognostic value of tumor downstaging and sterilization after preoperative radiotherapy for rectal cancer. PATIENTS AND METHODS: Between 1977 and 1994, 167 patients with a histologically proven adenocarcinoma underwent preoperative radiotherapy (median dose, 44 Gy; mean time before surgery, 5 weeks). Pathologic specimens were reviewed by the same pathologist in order to specify the modified Astler Coller classification (MAC) and to quantify residual tumor cell density (RTCD). RESULTS: According to the MAC, there were nine stage 0 (5%), 10 stage A (6%), 103 stage B1-B3 (62%) and 45 stage C1-C3 (27%) tumors. Seventeen per cent and 56% of the patients who received a dose > or = 44 Gy presented with stage 0-A and stage B1-B3 tumors, respectively, compared to 4 and 69% of those who received a dose < 44 Gy (P = 0.04). Tumor differentiation and a longer interval before surgery were significantly associated with more frequent downstaging. According to the RTCD, 62 tumors (37%) showed no or only rare foci of residual tumor cells; 62 (37%) showed an intermediate RTCD and 43 (26%) a high RTCD. No predictive factor of RTCD was statistically significant. Only post-operative staging was a significant prognostic factor (P < 0.01). CONCLUSION: The favourable influence of higher doses of preoperative radiotherapy on pathologic stage has been observed. Tumor differentiation and time before surgery were the other significant predictive factors of tumor downstaging. Even after preoperative radiotherapy, post-operative staging retained its prognostic value.

Adenocarcinoma↗

Erythromycin elicits opposite effects on antro-bulbar and duodenal motility: analysis in diabetics by cineradiography.

We have previously demonstrated by cineradiography analysis that erythromycin (Ery) increases antral contractility and antropyloric coordination in diabetics. The aim of this study was to further characterize antro-bulbar and duodenal motility after Ery i.v. administration. Fourteen diabetic patients (mean age 61.2 years) were randomly allocated to receive either 100 or 500 mg of Ery intravenously 4 hours after a standard solid liquid meal. After ingestion of a barium sulfate suspension, a series of 15 fluorographic plates (one every two seconds) was performed. the same procedure was repeated twice for each subject with a delay of 3 days once before and once after Ery. Antral, bulbar and duodenal areas and evolution diagrams were calculated in baseline conditions and after Ery administration using a graphic table connected to a microcomputer. No differences were found between the two doses of the drug. Ery significantly decreased antral (1284 +/- 268 mm2 vs 704 +/- 181 mm2; P < 0.01) and bulbar areas (127 +/- 26 mm2 vs 73 +/- 21 mm2; P < 0.01). In contrast, duodenal areas were significantly increased after Ery (875 +/- 112 mm2 vs 575 +/- 112 mm2; P < 0.01). This study suggests that the known prokinetic effect of Ery on gastric emptying seen in diabetic patients could be related to an increase of motility in the antrum and in the bulb simultaneously with a relaxation in the duodenum.

Adult↗

[Scintigraphic detection of gastrointestinal hemorrhage. Value and limitations].

A technetium-99m labelled red blood cell scintigraphy was performed in 51 patients with an unexplained gastro intestinal bleeding. Static images were acquired on the injection day then at 24 hours. Forty one patients had a positive scintigraphy. In 13 patients with a positive scintigraphy, on the injection day (5 cases) and later (8 cases), no intestinal bleeding was identified in spite of further investigations guided by scintigraphy. In 24 patients, with a positive scintigraphy on the injection day (20 cases) and later (4 cases), an intestinal lesion was identified and treated; data were confirmed in 19 cases: there were 15 colon lesions, localized on caecum in 10 cases and 4 small bowel lesions. Clinical value and limitations of the investigation are discussed. The scintigraphic localization is usually accurate if the abnormal focus activity is noticed on the injection day. It helps to guide further investigations of the bleeding site. This non invasive method should be performed more quickly to help to localize intestinal bleeding which poses a diagnostic problem.

Adolescent↗

[Obligatory surgery after endoscopic sphincterotomy for the treatment of stones in the common bile duct].

Endoscopic sphincterotomy is the treatment of choice for stones in the common bile duct in patients with a high operative risk. However, when this modality is insufficient or fails, these patients need to be operated. The authors have operated 14 patients under these conditions. In addition to the cholecystectomy performed in 9 patients who still retained their gallbladder, the common bile duct was cleared in 3 cases and drained by means of choledochoduodenal anastomoses in 10 cases. Three patients developed complications and one of them died. Endoscopy and surgery appear to be complementary in this indication. Sphincterotomy should be proposed as first-line treatment as, even in the case of incomplete disobstruction, it enables high-risk patients to be operated under better conditions.

Aged↗

Scintigraphy in duodeno-gastric reflux: a new method of quantification.

A prospective study is undertaken in order to demonstrate the ability of scintigraphy with a non compartmental analysis to quantitate the duodeno-gastric reflux. 24 patients have been examined, sitting in front of a gamma camera: 12 with an endoscopically proved reflux and 12 normal subjects or volunteers. About 15 min after an injection of 148 to 222 MBq 99Tcm-IDA they were given a meal labelled with 37 MBq 113Inm-DTPA. Images were recorded for 2 h. Equal size gastric and duodenal ROIs were selected over the duodenum and stomach, avoiding overlap with neighbouring organs. The reflux index based upon the occupancy principle is calculated from the gastric and duodenal curves. It is the ratio between the gastric and duodenal ROI IDA fluxes. The value of the reflux index is 3 +/- 1.8% in normal subjects and 45 +/- 33% in pathological cases. Our method, which does not require intubation, quantitatively evaluates biliary reflux independently of injected dose and hepatic or gallbladder function.

Adult↗

Paper stamp checklist tool enhances asthma guidelines knowledge and implementation by primary care physicians.

BACKGROUND: The Canadian Clinical Practice Guidelines (CPGs) for the management of asthmatic patients were last published in 1999, with updates in 2001 and June 2004. Large disparities exist in the implementation of these guidelines into clinical practice. OBJECTIVE: The present study evaluated the knowledge of Quebec-based primary care physicians regarding the CPGs, as well as patient outcomes before and after introducing physicians to a new clinical tool--a memory aid in the form of a self-inking paper stamp checklist summarizing CPG criteria and guidelines for assessing asthmatic patient control and therapy. The primary objective of the present study was to assess whether the stamp would improve physicians' knowledge of the CPGs, and as a secondary objective, to assess whether it would decrease patient emergency room visits and hospitalizations. METHODS: A prospective, randomized, controlled study of 104 primary care physicians located in four Quebec regions was conducted. Each physician initially responded to questions on their knowledge of the CPGs, and was then randomly assigned to one of four groups that received information about the CPGs while implementing an intervention (the stamp tool) aimed at supporting their decision-making process at the point of care. Six months later, the physicians were retested, and patient outcomes for approximately one year were obtained from the Régie de l'assurance maladie du Québec. RESULTS: The stamp significantly improved physicians' knowledge of the CPGs in all Quebec regions tested, and reduced emergency room visits and hospitalizations in patients who were followed for at least one year. CONCLUSION: A paper stamp summarizing CPGs for asthma can be used effectively to increase the knowledge of physicians and to positively affect patient outcomes.

Asthma↗

[Gastric stromal tumor with osteoclast-like multinucleated giant cells during Lynch II syndrome].

We report an unusual case of gastric tumor: a stromal tumor with osteoclast-like giant cells. This type of cells has been described in epithelial tumors, especially in adenocarcinoma of the pancreas, lung, thyroid and breast. It has also been reported in smooth cell tumors such as uterine leiomyosarcoma and malignant fibrous histiocytoma. In our patient, this gastric stromal tumor with osteoclast-like giant cells was diagnosed in a man with adenocarcinoma of the colon in the context of a familial cancer syndrome. This is the first report of stromal tumor with osteoclast-like giant cells associated with Lynch syndrome.

Adenocarcinoma↗