[Long-term outcome of neoadjuvant radiochemotherapy followed by surgery for esophageal cancer: a single institution retrospective study of 102 patients]. / Résultats à long terme de la chimioradiothérapie néoadjuvante des cancers de l'œsophage: étude rétrospective monocentrique sur 102 patients.

PURPOSE AND OBJECTIVES: To report survival and morbidity of a large homogeneous cohort of patients with a locally advanced esophageal or cardia carcinoma and put in evidence predictive factors of locoregional control and survival. PATIENTS AND METHODS: Hundred and two patients were treated at the university hospital of Tours between 1990 and 2010 and received neo-adjuvant chemoradiation therapy with external irradiation (40Gy-44Gy) and two courses of chemotherapy (5-fluoro-uracile and cisplatine). Esophagectomy associated with lymph node dissection was performed about ten weeks after the end of chemoradiation therapy. RESULTS: The median follow-up was 22.4 months [6-185 months]. The overall survival rates at 2 and 5years were 53% and 27%, respectively. The median overall survival was estimated at 27months. The overall 2-year survival between patients "responders" and patients "non-responders" was 67% vs 26%, respectively (P<0.0001). In case of histological response, there was a benefit in terms of overall survival (P<0.0001), locoregional control (P<0.0036) and disease-free survival (P<0.001). Overall survival at 2years was 64% for ypN0 group vs 32% for ypN1 group (P<0.0001). The median survival was estimated at 37months against 15months in the absence of lymph node involvement (P<0.0001). CONCLUSION: Our results in terms of survival, tolerance and morbidity and mortality were comparable to those in the literature. Complete histological response of lymph node was associated with an improvement of local control, disease-free survival and overall survival.

Changes in growth and maturation parameters of Pacific sardine Sardinops sagax collected off California during a period of stock recovery from 1994 to 2010.

Whether fluctuation in density influenced the growth and maturation variables of three aggregated cohorts (fish born during the 1986-1993, 1996-2003 and 2004-2008 periods) of Pacific sardine Sardinops sagax caeruleus collected off the Californian coast from 2004 to 2010 was investigated. Using a von Bertalanffy mixed-effects model with aggregated cohorts as covariates, estimated growth rate significantly covaried with aggregated cohorts. Growth rate (K) was modelled as a fixed effect and estimated to be 0.264 ± 0.015 (±s.e). Statistical contrasts among aggregated cohorts showed that the 1996-2003 cohorts had a significantly lower growth rate than the other two aggregated cohorts. The theoretical age at length zero (t0) and the standard length at infinity (L(S∞)) were modelled as random effects, and were estimated to be -2.885 ± 0.259 (±s.e) and 273.13 ± 6.533 mm (±s.e). The relation of ovary-free mass at length was significantly different among the three aggregated cohorts, with the allometric coefficient estimated to be 2.850 ± 0.013 (±s.e) for the S. sagax population. The age-at-length trajectory of S. sagax born between 1986 and 2008 showed strong density dependence effects on somatic growth rates. In contrast to the density-dependent nature of growth, the probability to be mature at-size or at-age was not significantly affected by aggregated cohort density. The size and the age-at-50% maturity were estimated to be 150.92 mm and 0.56 years, respectively. Stock migration, natural fluctuations in biomass and removal of older and larger S. sagax by fishing might have been interplaying factors controlling growth parameters during 1986-2010.

Comparison between a guaiac and three immunochemical faecal occult blood tests in screening for colorectal cancer.

BACKGROUND: The aim of this study was to compare the performance of the guaiac-based faecal occult blood test (G-FOBT), with that of three immunochemical faecal occult blood tests (I-FOBT) which allow automatic interpretation. PATIENTS AND METHODS: Under the French organised screening programme, 85,149 average-risk individuals aged 50-74 participating in the third screening round, performed both the G-FOBT (Hemoccult-II test) and one of the I-FOBTs: FOB-Gold, Magstream and OC-Sensor. RESULTS: Given the chosen threshold, the positivity ratio between the different I-FOBTs and the G-FOBT was 2.4 for FOB-Gold, 2.0 for Magstream and 2.2 for OC-Sensor (P=0.17). The three I-FOBTs were superior to the G-FOBT for colorectal cancer (CRC) detection. The ratios for detection rates were 1.6 (FOB-Gold), 1.7 (Magstream) and 2.1 (OC-Sensor) (P=0.74). For non-invasive CRC they were, respectively, 2.5, 3.0 and 4.0 (P=0.83) and for advanced adenomas 3.6, 3.1 and 4.0 (P=0.39). CONCLUSIONS: This study provides further evidence that I-FOBT is superior to G-FOBT. None of the three I-FOBTs studied appeared to be significantly better than the others.

Efficacy of irinotecan in combination with 5-fluorouracil (FOLFIRI) for metastatic gastric or gastroesophageal junction adenocarcinomas (MGA) treatment.

OBJECTIVES: The most commonly used schedules are 5-FU in combination with CDDP with or without epirubicin (ECF) or docetaxel (TCF) in treatment of MGA patients (pts), independently of HER status. We evaluated the efficacy of FOLFIRI regimen in a large retrospective series of MGA pts. METHODS: Two hundred and twelve pts from 13 French centers were treated with at least one cycle of FOLFIRI (irinotecan 180 mg/m2 intravenous (i.v.) over 90 minutes on day 1 with folinic acid (FA) 400mg/m2 i.v. over two hours followed by 5-FU 400mg/m2 i.v. bolus then 5- FU 2400 mg/m2 continuous infusion over 46 hours on day 1, repeated every 14 days). Primary tumour sites were 120 (58%) stomach and 92 (42%) gastroesophageal junction. FOLFIRI was administered as first-line in 137 (65%) pts and as later-line in 75 (35%) pts for MGA. RESULTS: There was no difference between chemonaive and not chemonaive pts treated as firstline in terms of response rate 37% (95% CI: 25-50) vs 44% (95% CI: 21-69), median PFS, 6.7 (95% CI: 5.5-9.9) vs 5.3 months (95% CI: 3.6-6.9) (P = 0.25), and OS, 13.1 (95% CI: 11.7-18.7) vs 8.8 months (95% CI: 7.3­15.6) (P = 0.19), respectively. There was no difference between pts treated as second or later-line in terms of response rate 20% (95% CI: 8-39) vs 22% (95% CI: 6-48), median PFS, four months (95% CI: 2.8-5.4) vs 3.5 months (95% CI: 2.3-4.5) (P = 0.56), and OS, 10.4 months (95% CI: 5.4-14.4) vs 5.3 months (95% CI: 3.5-11.3) (P = 0.58), respectively. The global grade 3-4 toxicities were: diarrhea 11%, vomiting 9%, neutropenia 18%, febril neutropenia 4% (one toxic death). CONCLUSIONS: This retrospective study confirms the activity and good tolerance of FOLFIRI regimen in MGA as first-line as well as later-line.

Pre-treatment lymphopenia as a prognostic biomarker in colorectal cancer patients receiving chemotherapy.

BACKGROUND: Lymphopenia is a predictor of the efficacy and hematological toxicity of chemotherapy in various advanced cancers. There is little data about this relationship in colorectal cancer. In this retrospective study, the influence of pretreatment lymphopenia on hematological toxicity and the efficacy of chemotherapy was investigated in colorectal cancer patients. PATIENTS AND METHODS: In total, 260 patients were included in the study. Correlations between pre-treatment lymphopenia (lymphocyte count < 1,000/µl) and the occurrence of hematological toxicity and efficacy of first-line palliative chemotherapy were investigated. RESULTS: Lymphopenia was found in 49/260 (19%) patients. Ten of these patients with lymphopenia (20.4%) experienced severe hematological toxicity compared with 17 of the remaining 211 (8%) patients (P = 0.01). Lymphopenia was identified as an independent factor for hematological toxicity. Among patients who received palliative chemotherapy, the objective response rate was significantly lower in lymphopenic patients than in the other patients (12.5% vs. 40.2%; P = 0.004). Lymphopenia was strongly associated with shorter progression-free survival (median 4 vs. 7 months; P = 0.033) and shorter overall survival (median 16 vs. 24 months, P = 0.024). Multivariate analysis revealed that lymphopenia had an independent effect on survival. CONCLUSIONS: Our findings show that lymphopenia is an independent predictive factor for both hematological toxicity and efficacy of chemotherapy in colorectal cancer. Pre-treatment lymphocyte count may represent a simple and new predictive biomarker of chemotherapy effects in colorectal cancer patients.

Circulating free tumor DNA and colorectal cancer.

Cancer is characterized by multiple somatic genetic and epigenetic alterations that could be useful as molecular markers for detecting tumor DNA in different bodily fluids. In patients with various diseases as well as in healthy subjects, circulating plasma and serum carry small amounts of non-cell-bound DNA. In this free circulating DNA, tumor-associated molecular alterations can be detected in patients who have cancer. In many instances, the alterations identified are the same as those found in the primary tumor tissue, thereby suggesting tumor origin from a fraction of the circulating free DNA. In fact, various types of DNA alterations described in colorectal cancer have been detected in the circulating free DNA of patients with colorectal cancer. These alterations include KRAS2, APC and TP53 mutations, DNA hypermethylation, microsatellite instability (MSI) and loss of heterozygosity (LOH). Also, advances in polymerase chain reaction (PCR)-based technology now allow the detection and quantification of extremely small amounts of tumor-derived circulating free DNA in colorectal cancer patients. The present report summarizes the literature available so far on the mechanisms of circulating free DNA, and on the studies aimed at assessing the clinical and biological significance of tumor-derived circulating free DNA in colorectal cancer patients. Thus, tumor-derived circulating free DNA could serve as a marker for the diagnosis, prognosis and early detection of recurrence, thereby significantly improving the monitoring of colorectal cancer patients.

[Decision process in oncology: the importance of multidisciplinary meeting]. / La réunion de concertation pluridisciplinaire : quelle place dans la décision médicale en cancérologie ?

Multidisciplinary meeting (MDM) in oncology has been institutionalised in France by the Cancer Plan. This study aims to determine the place of MDM in the decision process. From November 2004 to July 2005, we observed 29 meetings at the Tours Hospital and 324 case presentations, 80 in orthopaedics, 151 in gastroenterology and 93 in chest medicine. Forty physicians attending the meetings answered a questionnaire exploring their opinions on MDM and the collegial decision. We found that MDM is mostly the place for technical discussions and that patients' wishes are rarely addressed. The different medical specialities are well represented but we observed that only physicians attend MDM. Decisions for straightforward cases are rapidly validated. For more complex clinical situations (25 to 40% of case presentations), the multidisciplinary approach allows to adapt guidelines or to choose alternative treatments. All the physicians interviewed express that MDM legitimates the medical decision. It occurs that they disagree with the RCP decision. We discuss how MDM impacts on the medical decision as well as the shift from the individual decision to the collective one, particularly in term of responsibility.

Towards Excellence in Asthma Management: final report of an eight-year program aimed at reducing care gaps in asthma management in Quebec.

BACKGROUND AND OBJECTIVES: Asthma care in Canada and around the world persistently falls short of optimal treatment. To optimize care, a systematic approach to identifying such shortfalls or 'care gaps', in which all stakeholders of the health care system (including patients) are involved, was proposed. METHODS: Several projects of a multipartner, multidisciplinary disease management program, developed to optimize asthma care in Quebec, was conducted in a period of eight years. First, two population maps were produced to identify regional variations in asthma-related morbidity and to prioritize interventions for improving treatment. Second, current care was evaluated in a physician-patient cohort, confirming the many care gaps in asthma management. Third, two series of peer-reviewed outcome studies, targeting high-risk populations and specific asthma care gaps, were conducted. Finally, a process to integrate the best interventions into the health care system and an agenda for further research on optimal asthma management were proposed. RESULTS: Key observations from these studies included the identification of specific patterns of noncompliance in using inhaled corticosteroids, the failure of increased access to spirometry in asthma education centres to increase the number of education referrals, the transient improvement in educational abilities of nurses involved with an asthma hotline telephone service, and the beneficial effects of practice tools aimed at facilitating the assessment of asthma control and treatment needs by general practitioners. CONCLUSIONS: Disease management programs such as Towards Excellence in Asthma Management can provide valuable information on optimal strategies for improving treatment of asthma and other chronic diseases by identifying care gaps, improving guidelines implementation and optimizing care.

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.

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.

'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.

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.

Acute acalculous cholecystitis associated with Q fever: report of seven cases and review of the literature.

Q fever is a worldwide-occurring zoonosis caused by Coxiella burnetii. There are various clinical manifestations of acute Q fever, of which acute cholecystitis is a very rare clinical presentation. This study reports seven cases of acute cholecystitis associated with Coxiella burnetii and reviews two other cases from the literature. All patients were admitted to hospital for fever and abdominal pain in the right upper quadrant. Abdominal echography showed a distended gallbladder with biliary sludge without concrements in eight cases and with a single stone in one case. Diagnosis was made by specific serological investigation (microimmunofluorescence assay) for Coxiella burnetii. All nine patients were cured, six after laparoscopic cholecystectomy and three with antibiotics only. Histological examination of the gallbladders showed inflammation in five cases, although Coxiella burnetii was not detected by immunohistochemistry. The results show that laboratory investigations in patients admitted to hospital for symptoms consistent with acute acalculous cholecystitis should include a systematic search for Coxiella burnetii.

[Morbidity and mortality of acute pancreatitis. Prospective study in a French university hospital]. / Morbidité et mortalité de la pancréatite aiguë. Evaluation prospective dans un centre hospitalier universitaire français.

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.

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.

[Gastric stromal tumor with osteoclast-like multinucleated giant cells during Lynch II syndrome]. / Tumeur stromale gastrique à cellules géantes multinucléées de type ostéoclastique au cours d'un syndrome de Lynch II.

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.

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.

[Gastric granulocytic sarcoma revealed by a massive digestive hemorrhage]. / Sarcome granulocytaire gastrique révélé par une hémorragie digestive massive.

We report the case of a 37-year-old-man having a chronic myelogenous leukemia, who presented, one month after a splenic acutization, massive gastrointestinal bleeding from ulcerated nodules of the gastric fundus. The histologic examination of one of these nodules showed granulocytic sarcoma. In spite of an endoscopic treatment by sclerotherapy with adrenalined serum, the death occurred during a hemorrhagic recurrence. This observation, which is the third case reported of gastric granulocytic sarcoma during the acutization of a myelogenous chronic leukemia, and the first revealed by fatal gastrointestinal bleeding, shows the particular gravity of gastrointestinal bleeding complicating granulocytic sarcoma.