[Intracranial ependymomas in adult patients. Diagnosis and histological prognostic factors]. / Ependymomes intracrâniens de l'adulte. Diagnostic histologique et facteurs histopronostiques.

BACKGROUND: Intracranial ependymomas are rare in adults and histopathological prognostic factors are poorly determined. PURPOSE: A retrospective multicentric study was conducted in France in order to assess the prognostic value of histology. MATERIAL: Between 1990 and 2004, 216 adult patients with newly diagnosed ependymomas were treated in 19 French centers. Eligibility required institutional histopathological confirmation of an ependymoma and available clinical history and MRI features (see comparison paper). METHODS: Histological preparations and one paraffin embedded block from each patient were sent to Pr D. Figarella-Branger in Marseille. Central review by four neuropathologists (D. Figarella-Branger, A. Maues de Paula, C. Fernandez and A. Jouvet) was performed. Specimens for which all pathologists agreed with the histological diagnosis of ependymomas were included, whereas cases for which all disagree were excluded and reclassified. In the event of doubt and/or discrepancies between pathologists immunostaining was performed in order to reach a consensus diagnosis. Diagnostic of ependymomas was confirmed in 121 cases (56%). In theses cases, ependymomas were classified according to the WHO system (subtype and grade). The potential prognostic value (overall survival OS and disease free survival DFS) of the following histological parameters was examined: perivascular pseudorosettes, ependymal rosettes, hyalinized vessels, mitotic index, microvascular proliferation, necrosis, area of increased cellularity, nuclear atypia, brain invasion and Mib-1 labelling index. RESULTS: Among the 121 ependymomas, 88 were grade II (47 classic, 17 cellular, 2 papillar, 6 clear cells and 16 tanicytic) and 33 grade III. WHO grading, occurrence of microvascular proliferation, necrosis, nuclear atypia and high proliferative index were correlated with both OS and DFS. Moreover, quantification of certain parameters enabled a reproducible grading system correlated with both OS and DFS.

Polysialylated-neural cell adhesion molecule expression in rat pituitary transplantable tumors (spontaneous mammotropic transplantable tumor in Wistar-Furth rats) is related to growth rate and malignancy.

Pituitary adenomas are usually benign neuroendocrine tumors. However, some of those that are histopathologically undistinguishable behave aggressively and metastasize. The polysialylated neural cell adhesion molecule (PSA-NCAM), which is highly expressed during the development of the brain and pituitary, is detected in some neuroendocrine tumors and might be relevant as a prognostic marker in pituitary tumors. In the present study, we have searched for PSA-NCAM expression in four lineages of rat pituitary transplantable tumors (SMtTW). Each lineage, maintained by serial tumor grafts under the kidney capsule and skin, differed in its GH/Prl secretion, growth rate, and malignant behavior. PSA-NCAM expression, detected by immunohistochemistry and Western blotting and quantified by ELISA, varied according to the SMtTW lineage. The benign tumors, SMtTW2, with a low growth rate never expressed PSA-NCAM. Another benign lineage, SMtTW3, with a high growth rate expressed a low amount of PSA-NCAM. The highest PSA-NCAM expression was seen in tumors that grew beneath the skin, invaded the kidney, and metastasized (SMtTW4). Tumors of the SMtTW10 lineage, which behaved as either benign or malignant tumors, were heterogeneous in terms of PSA-NCAM expression. In this rat transplantable pituitary tumor model, PSA-NCAM expression correlated in decreasing order with: (a) invasiveness (P < 0.0001), (b) metastases (P = 0.004), (c) ability to grow under the skin (P = 0.006), and (d) growth rate under the kidney capsule (P < 0.01), but not with hormone secretion (r = 0.207). This model, which is very similar to the human pathology, suggests that PSA-NCAM evaluation is of interest in the diagnosis of malignancy and the prognosis of human pituitary tumors. In addition, the SMtTW tumors could be instrumental in evaluating the effects of new therapeutic agents modulating PSA-NCAM expression.

Echocardiography predicts embolic events in infective endocarditis.

OBJECTIVES: The aim of our study was to assess the value of transesophageal echocardiography (TEE) in predicting embolic events (EEs) in a large group of patients with definite endocarditis according to the Duke criteria, including silent embolism. BACKGROUND: The value of echocardiography in predicting embolism in patients with endocarditis remains controversial. Some studies reported an increased risk of embolism in patients with large and mobile vegetations, whereas other studies failed to demonstrate such a relationship. METHODS: Multiplane transesophageal echocardiograms of 178 consecutive patients with definite infective endocarditis (IE) were analyzed. The incidence of embolism was compared with the echocardiographic characteristics (localization, size and mobility) of the vegetations. To detect silent embolism, cerebral and thoraco-abdominal scans were performed in 95% of patients. RESULTS: Among 178 patients, 66 (37%) had one or more EEs. There was no difference between patients with and without embolism in terms of age, gender and left valve involved. On univariate analysis, Staphylococcus infection, right-side valve endocarditis and vegetation length and mobility were significantly related to EEs. A significant higher incidence of embolism was present in patients with vegetation length >10 mm (60%, p < 0.001) and in patients with mobile vegetations (62%, p < 0.001). Embolism was particularly frequent among 30 patients with both severely mobile and large vegetations (> 15 mm) (83%, p < 0.001). On multivariate analysis, the only predictors of embolism were vegetation length (p = 0.03) and mobility (p = 0.01). CONCLUSIONS: Our study shows that the presence of vegetations on TEE is predictive of embolism and that the morphologic characteristics of vegetations are helpful in predicting EEs in both mitral and aortic valve IE. It also suggests that early operation may be recommended in patients with vegetations > 15 mm and high mobility, irrespective of the degree of valve destruction, heart failure and response to antibiotic therapy.

Thrombin-activatable fibrinolysis inhibitor antigen levels and cardiovascular risk factors.

Thrombin-activatable fibrinolysis inhibitor (TAFI) is a recently described fibrinolysis inhibitor that circulates in plasma as a procarboxypeptidase and is converted into an active form during coagulation. The physiological relevance of TAFI is not known, but it might be involved in pathways regulating fibrin deposition. Our aim was to determine the interindividual variability of plasma TAFI antigen values and their associations with conventional cardiovascular risk factors. Six hundred twenty-six consecutive patients (277 men) attending a metabolic ward for primary prevention were studied. TAFI antigen presented a large range of values, with a 2- to 3-fold increase between the 10th and 90th percentiles. No difference was observed between the 2 sexes. A significant correlation was observed between age and TAFI levels in women only. After adjustment for age, TAFI antigen was positively correlated in men for the waist-to-hip circumference ratio and blood pressure, whereas no significant correlation was observed in women. Stepwise multiple linear regression analysis indicated a low contribution of the parameters studied to the variability of TAFI antigen levels; the waist-to-hip circumference ratio accounted for only 2% in men, and age accounted for only 3% in women. Results were compared with those of fibrinogen and plasminogen activator inhibitor-1; cardiovascular risk factors in men and women accounted for 16% and 9. 5%, respectively, of the fibrinogen variance and 36% and 32%, respectively, of the plasminogen activator inhibitor-1 variance. These observations did not attribute an important role to lifestyle characteristics in the control of TAFI antigen concentration in plasma. Because of the large interindividual variability of TAFI levels in plasma, genetic control may be involved.

The cyclothymic temperament in healthy controls and familially at risk individuals for mood disorder: endophenotype for genetic studies?

BACKGROUND: The modern concept of affective disorders focuses increasingly on the study of subthreshold conditions on the border of manic or depressive episodes. Indeed, a spectrum of affective conditions spanning from temperament to clinical episodes has been proposed by the senior author. As bipolar disorder is a familial illness, an examination of cyclothymic temperament (CT) in controls and relatives of bipolar patients is of major relevance. METHODS: We recruited a total sample of 177 healthy symptom-free volunteers. These controls were divided into three groups. The first one is comprised of 100 normal subjects with a negative familial affective history (NFH); the second of 37 individuals, with positive affective family history (PFH); and a third of 40 subjects, with at least one sib or first-degree kin with bipolar disorder type I according to the DSM-IV (BPR). The last two groups defined at risk individuals. We interviewed all subjects with CT, as described by the senior author. RESULTS: We found a statistically significant difference in the rates of CT between the subjects in BPR versus others. CT was also more prevalent in the PFH compared with NFH. Additionally, the simple numeration of the CT traits exhibited gradation in the distribution of individuals inside the NFH, PFH and BPR. Finally, categorically defined CT and CT traits predominated in females. LIMITATION and CONCLUSION: Although not all relatives of bipolar probands were studied, our results exhibit an aggregation of CT in families with affective disorder-and more specifically those with bipolar background. These results allow us to propose the importance of including CT for phenotypic characterization of bipolar disorder. Furthermore, our results support a spectrum concept of bipolar disorder, whereby CT is distributed in ascending order in the well-relatives of those with depressive and bipolar disorders. We submit that this temperament represents a behavioral endophenotype, serving as a link between molecular and behavioral genetics.

[Regression models for crude and relative survival: a comparative review]. / Revue comparative des modèles régressifs de survie brute et de survie relative.

BACKGROUND: Statistical analysis of lifetime data is frequently used in the biomedical area. Our objective was to present a comparative review of the different regression models according to the survival concept (crude survival or relative survival) in order to express guidelines. METHODS: From a methodological point of view, we compared a regressive crude survival model (Cox model) and regressive relative survival models for grouped data (Hakulinen and Tenkanen) and for individuals data (Esteve et al.). We illustrated our work with an analysis of survival data of 3,355 incident cases of breast cancer identified by a hospital registry. Comportment of the models was studied in situation where censors rates ranged from 31.7 to 96.5%. RESULTS: Because relative survival analysis takes into account natural mortality, the risk of death was smaller for women older than 50 years than for women aged from 35 to 49; this was not demonstrated in the crude survival analysis (Cox). Estimations obtained from Cox model were more accurate than those obtained from both studied regressive relative survival models. Estimations obtained from Esteve et al. model were not very different from those obtained from Hakulinen and Tenkanen model and they were more accurate. CONCLUSION: By definition, analysis of relative survival is more appropriate to estimate survival to a specific cause of death. It is preferable to use models based on individual estimation when data set is small or when the number of individual per strata is small.

[Pediatric supratentorial oligodendrogliomas: Marseilles and Lyons experiences]. / Les oligodendrogliomes supratentoriels de l'enfant. A propos des séries arseillaises et lyonnaises.

BACKGROUND AND PURPOSE: The goal of this study was to analyze the main aspects of oligodendrogliomas observed in children. METHOD: The records of 35 children aged 15 years or younger (23 from Marseilles and 12 from Lyons) were reviewed. Clinical signs and symptoms, imaging findings (CT scan and pre- and post-operative MRI), extent of surgical resection, histology according to the WHO and Ste-Anne grading and survival were analysed. Considering all these factors, a statistical analyzis was undertaken in order to identify prognostic factors. DISCUSSION AND CONCLUSION: Oligodendrogliomas are rare tumors in children. The most important differential diagnosis to discuss is dysembryoplastic neuroepithelial tumor. Our study allowed us to distinguish several subgroups of patients with a different prognosis: thalamic tumors with a dismal prognosis versus hemispheric tumors. A group of cortical tumors we called "DNT-like" (hemispheric cortical tumor, isolated epilepsy, without neurological deficit and reased ICP, without edema and mass effect on MRI) with an excellent prognosis like the group with epilepsy. Histological grading (grade A/grade B and grade II/grade III) is also a prognostic factor.

Q fever 1985-1998. Clinical and epidemiologic features of 1,383 infections.

In order to describe the clinical features and the epidemiologic findings of 1,383 patients hospitalized in France for acute or chronic Q fever, we conducted a retrospective analysis based on 74,702 sera tested in our diagnostic center, National Reference Center and World Health Organization Collaborative Center for Rickettsial Diseases. The physicians in charge of all patients with evidence of acute Q fever (seroconversion and/or presence of IgM) or chronic Q fever (prolonged disease and/or IgG antibody titer to phase I of Coxiella burnetii > or = 800) were asked to complete a questionnaire, which was computerized. A total of 1,070 cases of acute Q fever was recorded. Males were more frequently diagnosed, and most cases were identified in the spring. Cases were observed more frequently in patients between the ages of 30 and 69 years. We classified patients according to the different clinical forms of acute Q fever, hepatitis (40%), pneumonia and hepatitis (20%), pneumonia (17%), isolated fever (17%), meningoencephalitis (1%), myocarditis (1%), pericarditis (1%), and meningitis (0.7%). We showed for the first time, to our knowledge, that different clinical forms of acute Q fever are associated with significantly different patient status. Hepatitis occurred in younger patients, pneumonia in older and more immunocompromised patients, and isolated fever was more common in female patients. Risk factors were not specifically associated with a clinical form except meningoencephalitis and contact with animals. The prognosis was usually good except for those with myocarditis or meningoencephalitis as 13 patients died who were significantly older than others. For chronic Q fever, antibody titers to C. burnetii phase I above 800 and IgA above 50 were predictive in 94% of cases. Among 313 patients with chronic Q fever, 259 had endocarditis, mainly patients with previous valvulopathy; 25 had an infection of vascular aneurysm or prosthesis. Patients with endocarditis or vascular infection were more frequently immunocompromised and older than those with acute Q fever. Fifteen women were infected during pregnancy; they were significantly more exposed to animals and gave birth to only 5 babies, only 2 with a normal birth weight. More rare manifestations observed were chronic hepatitis (8 cases), osteoarticular infection (7 cases), and chronic pericarditis (3 cases). Nineteen patients were observed who experienced first a documented acute infection, then, due to underlying conditions, a chronic infection. To our knowledge, we report the largest series of Q fever to date. Our results indicate that Q fever is a protean disease, grossly underestimated, with some of the clinical manifestations being only recently reported, such as Q fever during pregnancy, chronic vascular infection, osteomyelitis, pericarditis, and myocarditis. Our data confirm that chronic Q fever is mainly determined by host factors and demonstrate for the first time that host factors may also play a role in the clinical expression of acute Q fever.

Prolonged QT interval and altered QT/RR relation early after radiofrequency ablation of the atrioventricular junction.

This study evaluated the paced QT interval in the days after radiofrequency ablation of the atrioventricular junction in patients with chronic rapid atrial fibrillation. There is an abnormality in the dynamics of the paced QT interval until the second day after ablation, resulting in an increased duration when the paced heart rate is <75 beats/min.

GENTIC: a computerized medical genetic case record system.

Gentic is a computerized system for the storage, recall, and analysis of data collected by the Medical Genetics Center in Marseille, France. It is based on a standard case report file that includes a full clinical description of all patients, results of cytogenetic investigations, and details of the genetic counseling provided. GENTIC has been used since 1975, and data on more than 5,000 families are accessible for study. This system has improved the quality of consultations, follow-up, and research. It provides data for epidemiological studies and for syndrome identification. This system is maintained at an annual cost of $3,000, salary costs not included, after an initial investment of $40,000.

MSH2 and MLH1 immunodetection and the prognosis of colon cancer.

MSH2 and MLH1 are proteins involved in DNA reparation. They are mutated in some forms of colon cancer, i.e. hereditary non-polyposis carcinomas and a subset of sporadic carcinomas. We have studied the expression of MSH2 and MLH1 in a retrospective series of 225 colorectal carcinomas by immunohistochemistry. The results were compared to molecular tests of microsatellite instability using amplification by PCR of BAT-25 and BAT-26 repeated sequences and to histoclinical data. Positivity of both proteins was never associated with MSI phenotype. MSH2 and/or MLH1 negative tumors were frequently tumors of the proximal colon; in this subpopulation or proximal tumors, MSH2 and/or MLH1 negativity was associated with a longer disease-free survival.

Simplification of the SAPS by selecting independent variables.

A series of 950 consecutive admissions to a multidisciplinary ICU were divided into 2 groups (group I = 450 and group II = 500). In the first group, 351 admissions were used to retrospectively create two scores: SAPS.R derived from the 14 original SAPS variables and SAPS.E derived from 22 variables (14 of SAPS plus 8 additional biological variables). Using a multiple logistic regression analysis only 5 variables were retained for SAPS.R and 7 for SAPS.E. In the second group, 446 patients were used to assess prospectively the discriminating power of SAPS, SAPS.R, SAPS.E by comparing the areas under the receiver operating characteristic (ROC) curves. There were no significant differences between the overall accuracies of these 3 scores. Adding biological variables did not improve the accuracy but the number of variables in the original SAPS could be greatly reduced.

Role of sun exposure on nevus. First study in age-sex phenotype-controlled populations.

BACKGROUND: These studies were designed to assess the influence of sun exposure on nevi in white people. To eliminate the confounding effect of age, sex, and phenotype, two parallel studies were conducted on people of the same age (17 to 24 years; median, 20 years old), sex (male), and phenotype: one in people with "red" phenotype (red or red-blond hair, white complexion on the inner part of the arm, and inability to tan) and one in people with "dark" phenotype (brown or black hair, dark complexion on the inner part of the arm, absence of freckles, and easy tanning without burning). RESULTS: In both groups, comparison of nevus counts on the inner and outer side of the upper extremities and comparison of mean density of nevi (number per square meter) in always-exposed and never-exposed skin show that the number of nevi is higher in sun-exposed areas. The density of large and atypical nevi was maximal on intermittently sun-exposed skin while the density of small nevi was maximal on always-exposed skin. The number of large nevi on intermittently exposed skin correlated with cumulative intensive exposure during beach recreation in the red phenotype group. The number of large nevi was significantly higher in red phenotypes who repeatedly experienced severe sunburns in their first 20 years of life. CONCLUSIONS: The number of nevi at the end of the second decade is influenced by cumulative sun exposure from birth. "Traumatizing" sun exposure, which is more frequent in the red phenotype than in the dark phenotype, has an influence on the number of large nevi and is therefore likely to make small nevi grow.

Relationship between neuropathy, hypertension and red blood cell Na/K ATPase in patients with insulin-dependent diabetes mellitus.

Hypertension has been proposed as an independent risk factor for diabetic neuropathy. In insulin-dependent diabetic (IDDM) patients suffering from neuropathy, red blood cell (RBC) Na/K ATPase is decreased. Such a decrease might be involved in the physiopathology of hypertension and therefore be the link between hypertension and neuropathy. To confirm this hypothesis, we studied 104 IDDM patients with a long duration of disease by looking at the association between neuropathy and hypertension and by comparing RBC Na/K ATPase activity in subgroups. The independent risk factors associated with neuropathy were hypertension, triglyceride level, diabetes duration and low RBC Na/K ATPase activity. Contrary to our expectations, Na/K ATPase was not decreased in hypertensive patients (294 +/- 16 nmol Pi/mg prot/h vs 303 +/- 9), but those treated with angiotensin converting enzyme (ACE) inhibitor had higher RBC Na/K ATPase activity than those treated with calcium blockers (355 +/- 15 nmol Pi/mg prot/h vs 216 +/- 10). These results confirm the association between neuropathy and hypertension, on the one hand, and neuropathy and decreased Na/K ATPase, on the other, and show that hypertension in IDDM patients was not associated with decreased RBC Na/K ATPase. Moreover, ACE inhibitor treatment in IDDM patients, whether hypertensive or not, was associated with higher levels of RBC Na/K ATPase, which could account for its beneficial effect on diabetic neuropathy.

Prognostic factors in intracranial ependymomas in children.

OBJECT: The occurrence of intracranial ependymomas in children is relatively infrequent, and their prognostic factors are still controversial, especially regarding histological composition. METHODS: A retrospective study was conducted of 37 children treated during the last 20 years for intracranial ependymomas at the Hôpital de la Timone. Both univariate and multivariate statistical analyses were performed to assess the prognostic relevance of patient age and sex, extent of tumor removal, location of the tumor (supratentorial compared with infratentorial, median compared with lateral), tumor histological composition, and adjuvant therapies in affecting the 5-year progression-free survival (PFS) rate and overall survival (OS) rate. The following histopathological features, either alone or in combination, were analyzed: endothelial proliferation, necrosis, loss of differentiating structures (present compared with absent), the number of mitotic figures per 10 hpf, and cellularity (number of nuclei/5 hpf). In addition, immunohistochemical detection of Ki-67 antigen was performed and the Ki-67 labeling index (LI) evaluated in all cases. The 5-year OS and PFS rates were 45% and 25%, respectively (median follow up 34 months). Four patients died of disease without remission (median 163 days) and disease in 21 patients relapsed: 18 in situ and three both in situ and distantly. On univariate analysis total surgical resection and median infratentorial location were associated with a better outcome (p < 0.002) for both OS and PFS. Loss of differentiating structures was associated with poor prognosis (p < 0.008) and the combination of necrosis, endothelial proliferation, and mitotic index greater than 5 was also a negative predictive factor for both OS (p < 0.002) and PFS (p = 0.02). The PFS time was shorter in patients younger than 4 years of age and in patients in whom a Ki-67 LI greater than 1 was found (p = 0.03 and 0.006, respectively). Adjuvant radiotherapy and chemotherapy were not relevant to prognosis. Moreover, among the 15 patients in whom total excision was achieved, OS was better in those who did not receive adjuvant therapies. In contrast, adjuvant therapies significantly enhanced PFS time in patients in whom tumor excision was incomplete. CONCLUSIONS: This study and analysis of the literature further highlight that total tumor removal is the treatment of choice for ependymomas in children. Postoperative measurement of residual tumor is required, especially because a subgroup of patients might be treated by surgery alone. Median infratentorial ependymomas have to be distinguished from the lateral type. Appropriate and reproducible histological parameters and Ki-67 LI are of interest as predictors of outcome.

Hydroxyapatite in experimental laryngotracheal reconstruction.

Current concepts in laryngotracheal reconstruction include lumen augmentation with interposition of autogenous costal cartilage. In an effort to reduce potential increased morbidity at the donor site, the use of porous hydroxyapatite was compared with autogenous costal cartilage in an experimental study. Ninety-nine New Zealand rabbits were randomly operated on to receive autogenous costal cartilage (n = 32), hydroxyapatite covered by a perichondrium graft (n = 33), or hydroxyapatite alone (n = 34). Rabbits were killed at 3 months after the surgery. Clinically (n = 85), no difference was found among the groups. Histologically (n = 81), grafts (n = 54) in the group receiving autogenous costal cartilage were greater than in those receiving the hydroxyapatite. Concerning the value of epithelial layer covering the graft, the rate of inflammation, the cricoid-graft interface, and the graft viability, no difference was noted among the groups. In the group in which no graft was found (n = 27), a fibrous bridge maintaining a cricoid distraction was noted in 23 cases. This study shows the possible value of hydroxyapatite in the animal model, but before clinical application, the natural course of the fibrous bridge must be documented.

Medical decision support systems: old dilemmas and new paradigms?

OBJECTIVES: The purpose of this paper is to examine past and present medical decision support systems and the environment in which they operate and to propose specific research tracks that improve integration and adoption of these systems in today's health care systems. METHODS: In preamble, we examine the objectives, decision models, and performances of past decision support systems. RESULTS: Medical decision support tools were essentially formulated from a technical capability perspective and this view has met limited adoption and slowed down new development as well as integration of these important systems into patient management work flows and clinical information systems. The science base of these systems needs to include evidence-based medicine and clinical practice guidelines and the paradigms need to be extended to include a collaborative provider model, the users and the organization perspectives. The availability of patient record and medical terminology standards is essential to the dissemination of decision support systems and so is their integration into the care process. CONCLUSION: To build new decision support systems based on practice guidelines and taking into account users preferences, we do not so much advocate new technological solutions but rather suggest that technology is not enough to ensure successful adoption by the users, the integration into practice workflow, and consequently, the realisation of improved health care outcomes.

Elaboration and formalization of current scientific knowledge of risks and preventive measures illustrated by colorectal cancer.

OBJECTIVES: Present the method used to elaborate and formalize current scientific knowledge to provide physicians with tools available on the Internet, that enable them to evaluate individual patient risk, give personalized preventive recommendations or early screening measures. METHODS: The approach suggested in this article is in line with medical procedures based on levels of evidence (Evidence-based Medicine). A cyclical process for developing recommendations allows us to quickly incorporate current scientific information. At each phase, the analysis is reevaluated by experts in the field collaborating on the project. The information is formalized through the use of levels of evidence and grades of recommendations. GLIF model is used to implement recommendations for clinical practice guidelines. RESULTS: The most current scientific evidence incorporated in a cyclical process includes several steps: critical analysis according to the Evidence-based Medicine method; identification of predictive factors; setting-up risk levels; identification of prevention measures; elaboration of personalized recommendation. The information technology implementation of the clinical practice guideline enables physicians to quickly obtain personalized information for their patients. Cases of colorectal prevention illustrate our approach. CONCLUSIONS: Integration of current scientific knowledge is an important process. The delay between the moment new information arrives and the moment the practitioner applies it, is thus reduced.

[5-fluorouracil, high dose folinic acid and mitomycin C in the treatment of advanced digestive cancers]. / Association 5-fluorouracile, acide folinique à haute dose et mitomycine C dans le traitement des cancers digestifs avancés.

Thirty five patients presenting with advanced unresectable digestive tract cancers were treated with high-dose folinic acid (200 mg/m2/d, i.v. bolus) followed by 5-fluorouracil (400 mg/m2 i.v. bolus) on day 2 of uneven courses (day 2, day 58, day 114...). There were 20 colorectal cancers, nine gastric cancers, two oesophageal cancers, two cholangiocarcinomas, one islet cell pancreatic carcinoma and one adenocarcinoma of unknown origin. An objective response was noted in 11/27 evaluable patients (40.7 +/- 19%): four complete and seven partial responses including three of the seven patients who previously failed to respond to 5FU-containing regimen, and eight of the 20 patients who received no prior chemotherapy. Objective responses were encountered in three of the five gastric cancers, five of the 17 colorectal cancers, one oesophageal cancer, one islet cell pancreatic carcinoma and one cholangiocarcinoma. The median duration of response was 6 months and overall median survival was 12 months (range: 1-48). There was one toxic death (non reversible medullar aplasia after the 1st course). This study confirms that this combination is an active regimen both for patients previously resistant to 5FU or untreated patients. It warrants further evaluation (perhaps with continuous 5FU infusions).

[Multivariate analysis of the prognostic and predictive factors of response to concomitant radiochemotherapy in epidermoid cancers of the esophagus. Value of immunodetection of protein p53]. / Analyse multifactorielle des facteurs pronostiques et prédictifs de réponse à la radiochimiothérapie concomitante dans les cancers épidermoïdes de l'oesophage. Intérêt de l'immunodétection de la protéine p53.

OBJECTIVE: The purpose of this study was to determine the prognostic value of the expression of protein p53, EGF receptors (EGR-R), cell proliferation antigen (Ki67) and DNA analysis by flow cytometry on per-endoscopic biopsies as well as the ability of these factors to predict response to concomitant chemoradiation in patients with squamous cell oesophageal carcinoma. METHODS: Sixty-two patients with squamous cell oesophageal carcinoma were prospectively included in this study. For 58 patients (51 men, 7 women; mean age: 59.1 +/- 9.3 years), clinical response to chemoradiation was correlated with the findings of flow cytometry (ploidy, % of cells in S-phase) and immunohistochemistry (p53, EGF-R, Ki67). There were 4 patients in stage I, 14 in stage II, 27 in stage III, and 13 in stage IV. Chemoradiation (2 cycles associating continuous 5FU 800 mg/m2/24 h from D1 to 5 and from D22 to 26, Cisplatyl 70 mg/m2 on D1 and D22; 15 Gy/5d from D1 to 5 and from D22 to 26), was performed prior to surgery in 19 patients (group I) and as the only treatment in 39 patients (group II), with a third cycle from D43. Clinical response was defined as complete or incomplete, ascertained by endoscopy and biopsy, 2 to 3 weeks after the end of chemoradiation. RESULTS: Mean survival in all 58 patients was 13.0 months. Survival was significantly longer in responders than in non responders (14.7 vs 9.6 months; P = 0.03). Among M0 patients, survival was not different in case of exclusive chemoradiation therapy or chemoradiation therapy followed by surgical excision (17.6 vs 13.0 months; NS). Monofactorial analysis showed that, in addition to response, the variables related to survival were stage, non-metastatic status, and absence of p53 surexpression. After multifactorial analysis according to the Cox model, the remaining variables were non-metastatic status, and absence of p53 surexpression. A complete response with negative biopsies was observed in 39 out of 58 patients, i.e. 67.3 +/- 12.1 % (group I: 12 out of 19; group II: 27 out of 39; NS). According to monofactorial analysis, 3 factors were predictive of complete response, i.e. non surexpression of p53 (P < 0.05) and tumour diameter (P = 0.04). After step-by-step logistic regression, non surexpression of p53 and tumour diameter continued to be predictive. The relative risk of a non-complete response was 5.46 if p53 was detected and 1.84 for each cm of added tumour diameter. These two factors were independent. CONCLUSIONS: In this study the predictors of complete response were absence of p53 surexpression and tumour diameter ascertained by CT-scan. Flow cytometry and Ki67 antigen had no prognostic value and were not predictors of response.