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J Maurel

Publications and source records attributed to J Maurel.

At least 19 recordsLinked to original sources

Phase II study with the combination of gemcitabine and DTIC in patients with advanced soft tissue sarcomas.

PURPOSE: Based on the promising results of a Phase I study with a combination of gemcitabine and DTIC performed in advanced soft tissue sarcoma (ASTS) patients, and due to the limited efficacy of second or third line therapies in those patients, we designed a Phase II study to determine the activity of this new regimen. METHODS: Patients with ASTS, measurable disease, pretreated with chemotherapy, received gemcitabine 1,800 mg/m2 infused over 180 min followed by DTIC 500 mg/m2 (one cycle), every 2 weeks. The pharmacokinetics (PK) of gemcitabine and 2',2'-difluorodeoxyuridine (dFdU), and the accumulation of gemcitabine triphosphate (dFdCTP) by peripheral blood mononuclear cells were studied. The influence of the sequence of administration on those parameters was examined to exclude potential drug interactions. RESULTS: Twenty-six patients received a total of 158 cycles (mean four cycles, range 1-18). Grade 3-4 anemia (23% of patients), granulocytopenia (46%) or thrombocytopenia (12%), and grade 3 increase in AST (18%), ALT (21%), or gamma-glutamyl-transferase (9%) were noted. Response rate in 23 patients was 4% (95% CI: 0-24%), and in 8 of 11 patients stable disease lasted > 6 months. Progression-free rate (PFR) at 3 and 6 months was, respectively, 48 and 28%, and median overall survival 37 weeks. Pooled data from the Phase I and Phase II studies showed clinical benefit in patients with leiomyosarcomas (LMS) (57%) and malignant fibrous histiocytomas (MFH) (33%). The sequence of administration did not influence PK of gemcitabine or dFdU. There was a trend (P = 0.11) toward a lower accumulation of dFdCTP when DTIC preceded gemcitabine. CONCLUSIONS: Although the remission rate was low, PFR figures indicate that this regimen has activity in patients with ASTS. It should be compared with DTIC, or other gemcitabine-containing combinations, in patients with LMS or MFH, to determine whether this combination offers advantages in PFR or in overall activity.

Adult↗

Phase I/II trial of doxorubicin and fixed dose-rate infusion gemcitabine in advanced soft tissue sarcomas: a GEIS study.

The aim of the study was to determine the dose-limiting toxicity and maximum tolerated dose of a first-line combination of doxorubicin and gemcitabine in adult patients with advanced soft tissue sarcomas and to explore its activity and toxicity, and the presence of possible interactions between these agents. Patients with measurable disease were initially treated with doxorubicin 60 mg m(-2) by i.v. bolus on day 1 followed by gemcitabine at 800 mg m(-2) over 80 min on days 1 and 8, every 21 days. Concentrations of gemcitabine and 2',2'-difluorodeoxyuridine in plasma, and gemcitabine triphosphate levels in peripheral blood mononuclear cells were determined during 8 h after the start of gemcitabine infusion. Myelosuppression and stomatitis were limiting toxicities, and the initial dose level was applied for the Phase II trial, where grade 3-4 granulocytopenia occurred in 70% of patients, grade 3 stomatitis in 46% and febrile neutropenia in 20%. Objective activity in 36 patients was 22% (95% CI: 9-35%), and a 50% remission rate was noted in leiomyosarcomas. Administration of doxorubicin preceding gemcitabine significantly reduced the synthesis of gemcitabine triphosphate. Clinical activity, similar to that of single-agent doxorubicin, and the toxicity encountered do not justify further studies with this schedule of administration.

Adult↗

A population-based study of the incidence, management and prognosis of hepatic metastases from colorectal cancer.

BACKGROUND: The aim of this population-based study was to evaluate the incidence, management and prognosis of patients with hepatic metastases related to colorectal cancer using data from the Digestive Cancer Registry of Calvados, France. METHODS: Of 1325 patients with colorectal cancer registered between January 1994 and December 1999, 358 developed hepatic metastases. Logistic regression was used to analyse prognostic factors. Survival analysis was carried out with Cox's proportional hazards model. RESULTS: Some 18.8 per cent of patients had synchronous metastases, while 29.3 per cent developed metastases at 3 years. Of patients with hepatic metastases, 17.3 per cent had a surgical resection, 40.2 per cent were treated with palliative chemotherapy and 42.5 per cent had symptomatic treatment. Factors associated with receiving symptomatic treatment only were age over 75 years and more than one metastasis, but not place of treatment. Median survival after a diagnosis of hepatic metastases was 10.7 (range 4.6-23.1) months. Significant adverse prognostic factors were: age over 75 years (P = 0.001), lymph node invasion of primary tumour (P = 0.024), bilateral distribution of metastases (P = 0.001), other metastases (P = 0.004) and symptomatic treatment only (P = 0.041). CONCLUSION: Despite improvement in treatment for hepatic metastases, age and extent of disease remain limiting factors for surgical resection and palliative chemotherapy.

Adult↗

[Inflammatory bowel disease and pregnancy: report of 76 cases and review of the literature].

OBJECTIVE: Obstetrical prognosis for women suffering from Crohn's disease and from ulcerative colitis, and consequences of pregnancy on inflammatory bowel diseases (IBD). PATIENTS AND METHODS: Retrospective study, of 76 pregnancies, after the diagnosis of IBD among 77 women (33 ulcerative colitis, 44 Crohn's disease). RESULTS: Pregnancy did not modify the evolutive profile of IBD. No particular gravity of IBD revealed during pregnancy or post-partum was noticed. The outcome of the 54 pregnancies associated with quiescent IBD was the same as in the general population. Five of ten pregnancies started during an active period of Crohn's disease or ulcerative colitis ended in fetal loss (3 spontaneous abortions, 2 medical terminations). In women with a first acute episode or IBD reactivation during pregnancy (n=12), one-third of the newborns were low weight for gestational age, one-third were born preterm and only one-third were term babies with normal weight. Vaginal delivery did not trigger development or exacerbation of perianal Crohn's disease (n=20). Cesarean section was performed in 2 with an ileal pouch-anal anastomosis (n=4) and 1 patient with an ileo-rectal anastomosis (n=3) to avoid injury to the anal sphincter. Ileostomy (n=2) did not contraindicate delivery. CONCLUSION: Control of IBD is the main obstetrical factor for prognosis. Starting pregnancy can be advised if the disease is quiescent, with rapid and efficient management of possible flare-ups. Delivery route must be determined on a case-by-case basis, each considering pregestational anal continence and the clinical presentation of the perineum.

Chronic Disease↗

Consensus meeting for the management of gastrointestinal stromal tumors. Report of the GIST Consensus Conference of 20-21 March 2004, under the auspices of ESMO.

BACKGROUND: The management of gastrointestinal stromal tumors (GIST) has evolved very rapidly in the last 4 years. The objectives of this international consensus meeting were to describe the optimal management procedures for patients with GIST in localized and advanced stages, as well as research issues for the future. MATERIALS AND METHODS: A panel of experts from six specialties, including pathology, molecular biology, imaging, surgery, medical oncology and methodologists for clinical practice guidelines from different European and extra European sarcoma societies were invited to a 2-day workshop. Several questions were selected by the organizing committee prior to the conference. Selected panelists reviewed the current levels of evidence for each point, and presented their conclusions during the meeting. These proposals were discussed, and consensus points were identified and categorized according to the Standard Options Recommandations (SOR) of the French Federation of Cancer Centers and National Comprehensive Cancer Network (NCCN). RESULTS: Thirty-two consensus points were identified, most from categories 2A of the NCCN and B2 of the SOR. Among these, the standard histological examination with immunohistochemical analysis using CD117, CD34, PS100, desmin and smooth muscle actin is considered standard. Molecular biology for the identification of KIT and PDGFRA mutation is an optional diagnostic procedure for GIST with negative CD117 staining, and otherwise is considered a research procedure. Complete tumor resection with negative tumor margins is the standard surgical treatment. Adjuvant imatinib after optimal tumor resection as well as neo-adjuvant imatinib remain experimental approaches to be performed within prospective clinical studies. Imatinib should be started at the date of diagnosis of metastatic relapse and given until development of intolerance or progressive disease. The optimal criteria for tumor response to imatinib remain to be delineated, and should include not only tumor size reduction or disease stabilization, but also reduction of tumor density (Hounsfield Units) on computed tomography and metabolic activity (i.e. reduction of FDG uptake on positron emission tomography). In a substantial proportion of patients, stable disease and even increase in tumor size may be associated with pathologic response to imatinib therapy, and available survival data indicate that the survival of these patients is similar to that of patients with conventional tumor response. Metastasis resection is an experimental procedure. CONCLUSIONS: Consensus points in clinical management of GIST as well as questions for future clinical trials were identified during this consensus conference on GIST management.

Benzamides↗

[Hospital registry of pancreatic tumors. Experience of the Hospital Clínic in Barcelona (Spain)].

OBJECTIVE: To describe the characteristics of patients included in the pancreatic tumor registry of the Hospital Clínic of Barcelona. PATIENTS AND METHOD: All patients with pancreatic tumors attended between July 1990 and March 2003 were registered. Data collection included: age, gender, date of diagnosis, diagnosis, histology, size, location and tumor stage, and treatment. The correlation between tumor stage and age, date of diagnosis, and tumor location was also evaluated. RESULTS: Six hundred thirty patients with pancreatic tumors were included, representing an incidence of 60 patients/year. The mean age was 66 years and the male-to-female ratio was 1,18:1. The most frequent lesion was malignant tumor of the pancreas (92%), and the most frequent histological type was pancreatic ductal adenocarcinoma (73%). The most frequent location was the head of the pancreas (64%). In 28% of the patients, pancreatic cancer was diagnosed in stage I and II. Resection was performed in 31% of patients, whereas 48% of the patients received no treatment. The ratio between local (stage I)/disseminated (stage IV) disease was 0,34. The ratio between stage I/IV increased with age, diagnosis prior to 1994, and tumor location in the head of the pancreas. CONCLUSION: Hospital tumor registries can be used to define the profile of the attended population, which can help to delineate the best diagnostic-therapeutic strategy and can be useful in clinical research.

Adult↗

Is there a role for (99m)Tc-anti-CEA monoclonal antibody imaging in the diagnosis of recurrent colorectal carcinoma?

AIM: To evaluate the usefulness of immunoscintigraphy with an anti-CEA monoclonal antibody fragment labelled with (99m)Tc for early detection of colorectal recurrence in patients with rising serum CEA levels. METHODS: Fifty-one consecutive patients (27 women, 24 men) with colorectal cancer (mean age 68.9+/-10.2 years) and rising CEA levels (16.2+/-18.2 ng/ml) were prospectively studied. Two immunoscintigraphy studies were performed in 8 patients (n=59). Immunoscintigraphy was performed after i.v. injection of 925 MBq of anti-CEA monoclonal antibody. Planar images of the thorax, abdomen and pelvis, as well as SPECT of the abdomen and pelvis were obtained at 4 and 24 hours after injection. In all cases an abdominal CT scan was previously performed. Findings were validated by histopathological analysis (28 cases) or by imaging and clinical follow-up of at least 6 months following the immunoscintigraphy (31 cases). RESULTS: Forty-one patients did not show recurrence during follow-up. We found 18 cases with confirmed diagnosis of extrahepatic abdominal or pelvic diseases, 11 cases with liver metastases, 9 in the thorax and 2 in the bone. In patients with pelvic and extrahepatic abdominal disease, immunoscintigraphy was positive in 18 cases (14 true positive, 4 false positive). From the 14 true positive only 7 cases had been detected by CT. Immunoscintigraphy was negative in the remaining 41 cases (37 true negative, 4 false negative). Therefore, the sensitivity and specificity for immunoscintigraphy in extrahepatic abdominal and pelvic disease were 78% and 90%, respectively. CT results showed a lower sensitivity of 61% (p<0.05) and specificity of 83%. Liver metastases were detected by CT in 9 cases, but only 2 of these were identified using immunoscintigraphy. CONCLUSION: Scintigraphy with anti-CEA monoclonal antibody fragment labelled with (99m)Tc is superior to CT for the detection of pelvic and extrahepatic abdominal recurrence of colorectal cancer, while CT is more sensitive in the detection of liver and lung metastases. Immunoscintigraphy has a limited usefulness in the detection of distant metastases, but it may be helpful in the diagnosis of suspected colorectal recurrence in patients with non-conclusive CT findings, when FDG-PET is not available.

Aged↗

[Evaluation of the efficacy and efficiency of a multidisciplinary unit for the treatment of patients with colorectal cancer].

INTRODUCTION: Because of the increased complexity of the diagnostic-therapeutic approach to colorectal cancer (CRC), these patients should be managed in specialized multidisciplinary units. The aim of this study was to evaluate the efficacy and efficiency of a CRC unit (CRCU) in the diagnostic-therapeutic management of these patients. PATIENTS AND METHODS: Two groups of 50 patients with colon cancer treated in our center before and after the implementation of the CRCU were selected. Fulfillment with the protocol in terms of tumoral staging, surgical and adjuvant treatment, follow-up, interval until treatment, hospital stay, morbidity and early mortality, and the overall duration of the diagnostic-therapeutic process was analyzed. In addition, clinical workload was evaluated and a cost-minimization analysis was performed. RESULTS: The CRCU reduced the interval until surgery (20.3 12.0 vs 28.0 20.4 days; p = 0.05), hospital stay (9.8 7.7 vs 14.5 9.3 days: p = 0.01), the time to the start of adjuvant treatment (29.4 10.2 vs 39.7 19.8 days; p = 0.03) and the overall duration of the process (60.4 23,8 vs 82.1 46.1 days; p = 0.05), representing a saving of 978.85 E per patient. This improvement took place despite an increase in clinical workload (24% in 5 years in relation to the number of admissions) and had no effect on morbidity (26 vs 24%; NS) or immediate mortality (6 vs 4%; NS). CONCLUSION: Specialized multidisciplinary units increase the efficacy and efficiency of the management of patients with CRC.

Aged↗

[Late intestinal fistula following implantation of parietal abdominal prostheses].

STUDY AIM: The aim of this retrospective study was to describe an unusual complication of the nonabsorbable meshes used for repair of incisional hernia or inguinal hernia. PATIENTS AND METHODS: This study included eight observations of intestinal fistulas that occurred between 1 and 13 years after using Mersilène (Dacron) mesh for repair of an incisional hernia (7 cases) and an inguinal hernia (1 case). There were 6 men and 2 women (mean age: 58 years, range: 35-85 years) with an external intestinal fistula (n = 6) or an internal intestinal fistula (n = 2). All the patients required a reoperation for extraction of the mesh and treatment of the bowel injuries. RESULTS: There was one secondary death in a 85 years old woman in relation with a vascular complication after incomplete excision of the prosthesis. In five patients out of six, there was a recurrence of the incisional hernia. CONCLUSION: The intestinal fistulas associated with prosthetic repair of the abdominal wall are mostly observed with intraperitoneal mesh but this factor is not exclusive. Their frequency after repair of incisional or inguinal hernia with non absorbable mesh is estimated between 0.3 and 3.5%. The use of nonabsorbable mesh should be limited to the indications of strict necessity, without any septic context or emergency surgery. The contact of the mesh with the bowel should be formally avoided.

Adult↗

Phase I trial of weekly gemcitabine at 3-h infusion in refractory, heavily pretreated advanced solid tumors.

Gemcitabine (2',2'-difluorodeoxycytidine) is a nucleoside analog with antitumor activity against a variety of malignancies. The critical enzyme cytidine kinase is saturated at plasma concentrations achieved after a 30-min infusion at conventional doses. Prolonged infusion time may yield higher intracellular dFdCTP concentrations. A phase I study was designed to determine the maximum tolerated dose (MTD) of gemcitabine, given by infusion for 3 h, in heavily pretreated patients. Twenty-seven patients (13 head and neck cancer, seven sarcoma, three esophageal cancer, three non-small-cell lung cancer and one ovarian cancer) were enrolled. Twenty patients were defined as refractory at first- or second-line chemotherapy. Four different entry dose levels (300, 400, 450 and 500 mg/m(2)) were evaluated for gemcitabine administered on days 1, 8 and 15 of a 28-day cycle. The MTD was defined as 450 mg/m(2), with granulocytopenia, thrombocytopenia and asthenia being dose limiting. The maximum grade III/IV patient toxicities for hemoglobin, leukocytes, neutrophils and platelets for all doses were 7, 19, 19 and 11%, respectively. Non-hematological toxicities included asthenia, nausea/vomiting and diarrhea. Thus, gemcitabine administered at a fixed 3-h infusion was well tolerated up to 450 mg/m(2) in heavily pretreated patients. Myelosupression and asthenia were dose-limiting toxicities.

Adult↗

Prognostic impact of bulky mediastinal lymph nodes (N2>2.5 cm) in patients with locally advanced non-small-cell lung cancer (LA-NSCLC) treated with platinum-based induction chemotherapy.

A group of 70 patients with locally advanced non-small-cell lung cancer (LA-NSCLC), treated in different phase II-III trials with platinum-based chemotherapy in two institutions, have been evaluated to identify potential baseline prognostic factors predicting their survival. The eligibility criteria were patients with stage IIIA (N2)-IIIB, Eastern Cooperative Oncology Group performance status 0.1 and less than 5% weight loss. All 37 patients with stage IIIA(N2) were treated with platinum-based induction chemotherapy followed by surgery plus radiotherapy if no progression was observed. The other 33 patients with stage IIIB were treated with platinum-based induction chemotherapy followed by conventional fractionation radiotherapy if no progression was observed. The overall response rate to induction chemotherapy was 40%. Median survival of the 70 patients was 13 months, with a 4-year survival of 15%. At univariate analysis, two prognostic factors correlated with survival: partial or complete response to induction chemotherapy (P<0.00001) and bulky mediastinal lymph nodes (N2>2.5 cm) (P=0.03). At multivariate analysis, only the response to induction chemotherapy retained statistical significance (P=0.00001). Randomized well-balanced prospective trials considering initially mediastinal N2 node size are needed to clearly establish the role of chemotherapy, surgery and radiotherapy in LA-NSCLC.

Adult↗

Colorectal cancer after a negative Haemoccult II test and programme sensitivity after a first round of screening: the experience of the Department of Calvados (France).

Colorectal cancers emerging after a negative Haemoccult II are described in the context of a first round of mass screening in the Department of Calvados (France), from April 1991 to the end of December 1994. People with a cancer occurring after a negative test until 31 December 1995 were identified by a local cancer registry. Incidence was calculated and the programme sensitivity was estimated. The incidence of cancer emerging after a negative test was 57.7 per 100000, i.e. half of the calculated incidence in the reference group (141.6 per 100000). These cancers did not differ from those of either the non-responder or reference groups, in particular for the stage of extension. The programme sensitivity was globally higher than that estimated in European trials: 77.2, 66.3 and 55.9%, 1, 2 and 3 years after the test respectively. Programme sensitivity was higher for distal colon cancer 1 year after the test, which is probably due to the relatively slow growth of this subsite.

Aged↗

Recent time trends in cancer of the oesophagus and gastric cardia in the region of Calvados in France, 1978-1995: a population based study.

The incidence of oesophageal cancer differs from country to country, and even between areas of the same country. Many studies in recent years have shown an upward trend of a particular histologic type: adenocarcinoma of the oesophagus. It is difficult to precisely locate adenocarcinomas situated at the junction between the oesophagus and the gastric cardia. Clear criteria to define and classify such tumours are essential in order to analyse their evolution. The present study describes the changing incidence of cancers of the oesophagus and gastric cardia according to histologic type from 1978 to 1995 in Calvados, the highest-risk French region with two different topographic classifications of adenocarcinomas: one based on Misumi's criteria and the other based on local extension of cancer. In total, 1835 cancers of the oesophagus and gastric cardia were diagnosed in this period. Incidence rates for oesophageal and gastric cardia cancers standardized on the world population were 24.4/10(5) and 2.4/10(5) in men and 1.4/10(5) and 0.4/10(5) in women, respectively. The time trend in the incidence of squamous cell cancers was downward in men -0.74 (P < 10(-6)) and stable in women +0.04 (P = 0.65). Regarding adenocarcinomas, with the classification based on Misumi's categories, there was a slight but significant upward trend for oesophageal adenocarcinoma in men [mean annual variation of +0.09 (P < 10(-5))] while the tendency was downward and significant for gastric cardia adenocarcinoma [mean annual variation of -0.09 (P < 10(-4))]. When adenocarcinomas of the oesophagus and those of the gastric cardia with oesophageal involvement are taken together (second classification), there was an upward trend which was not significant in men and was significant in women. There was no such upward trend in adenocarcinomas limited to the gastric cardia and/or involving the stomach. Because of the difficulties in determining accurate localization routinely in population-based studies, it seems sensible to preclude classification biases in recommending the grouping together of gastric cardia adenocarcinomas with oesophageal adenocarcinomas, at least with those among the latter occurring in the lower third of the oesophagus.

Adenocarcinoma↗

Evidence of improving survival of patients with rectal cancer in france: a population based study.

BACKGROUND: Over the past 20 years there have been many changes in the management of rectal cancer. Their impact on the overall population is not well known. AIMS: To determine trends in management and prognosis of rectal cancer in two French regions. SUBJECTS: 1978 patients with a rectal carcinoma diagnosed between 1978 and 1993. METHODS: Time trends in treatment, stage at diagnosis, operative mortality, and survival were studied on a four year basis. A non-conditional logistic regression was performed to obtain an odds ratio for each period adjusted for the other variables. To estimate the independent effect of the period a multivariate relative survival analysis was performed. RESULTS: Over the 16 year period resection rates increased from 66.0% to 80.1%; the increase was particularly noticeable for sphincter saving procedures (+30.6% per four years, p=0.03). The percentage of patients receiving adjuvant radiotherapy increased from 24.0% to 40.0% (p=0.02). The proportion of patients with Dukes' type A cancer increased from 17. 7% to 30.6% with a corresponding decrease in those with more advanced disease. Operative mortality decreased by 31.1% per four years (p=0.03). All these improvements have resulted in a dramatic increase in relative survival (from 35.4% for the 1978-1981 period to 57.0% for the 1985-1989 period). CONCLUSIONS: Substantial advances in the management of rectal cancer have been achieved, but there is evidence that further improvements can be made in order to increase survival.

Adolescent↗

[Rectal resection for cancer in Lower-Normandy. Loco-regional recurrences and survival. Results of a regional survey (1988-1993)].

OBJECTIVES AND METHODS: A retrospective regional study was set up to identify the determinants of loco-regional recurrences and those of survival after rectal resection for cancer. The studied population was constituted of 505 patients with resection for carcinoma of the rectum in Lower-Normandy from 1988 to 1993. RESULTS: The actuarial rate of loco-regional recurrence was 17.3 +/- 4% at 3 years. The only significant predictive factor of survival free of loco-regional recurrence was the Dukes' stage. Actuarial survival rate was 52.0 +/- 4% at 5 years, the corresponding relative survival rate being 64.6 +/- 6%. The only two independent prognostic factors were the sphincter-saving procedure and adjuvant radiotherapy. COMMENTARIES: The loco-regional recurrence rate after resection for rectal cancer is still high. Sphincter-saving procedure and adjuvant radiotherapy increase over the time. Since the study was retrospective, no definitive conclusions could be drawn. Nevertheless, they incite us to set up larger prospective regional studies including quality control of surgical procedures, radiotherapy protocols and histopathological reports.

Actuarial Analysis↗

[Indications and results of mucosal proctectomy with colo-anal anastomosis in villous disease of the rectum].

The objective of this study was to define the indication for proctectomy and colo-anal anastomosis in large rectal villous adenomas. The study population consisted of 20 patients (12 men and 8 women; mean age 63.6) who underwent rectal excision and colo-anal anastomosis from 1990 to 1997. The average size of tumors was 59.8 mm; 18 tumors were located in the lower third of the rectal ampulla; 8 patients had prior treatment (surgical or medical) before proctectomy. There were 13 straight colo-anal anastomoses and 7 constructed with colonic J pouch. Eighty percent of the anastomoses were defunctioned by a temporary stoma. The overall morbidity included one case of pelvic sepsis, two anastomotic strictures and one colonic trans-anal prolapse. One patient experienced persistent mild fecal incontinence and two others developed urogenital. The mean hospital stay was 14.4 days and 8.5 days for stoma closure. 8 tumors contained malignancy: 3 Tis, 4 T1 and 1 T2. In our opinion the extension, natural history or potential of occult malignancy of large rectal villous adenomas may requires rectal excision with colo-anal anastomosis with low morbidity and good functional results.

Adenocarcinoma↗