Seafloor litter from the continental shelf and canyons in French Mediterranean Water: Distribution, typologies and trends.

Seafloor litter has been studied both on the continental shelves (by trawling during 24 years) and in canyons (by ROV) of the French Mediterranean sea Water (FMW). On the continental shelf, mean densities range from 49.63 to 289.01 items/km2. The most abundant categories were plastic, glass/ceramics, metals and textiles. Trend analysis shows a significant increase in plastic quantities during the study period. Plastics accumulate at all depths, with heavier items being found in deeper areas, while the continental slope-break appears as a clean area. The spatial distribution of litter revealed the influence of geomorphologic factors, anthropic activities, shipping route, river inputs. All the canyons are affected by debris but coastal canyons (Ligurian Sea and Corsica) were more impacted than offshore canyons in the Gulf of Lion. The FMW appears to be highly polluted with regard to values found in other areas, but lower than those observed in the Eastern Mediterranean.

Mercury in organisms from the Northwestern Mediterranean slope: importance of food sources.

Mercury (Hg) is a global threat for marine ecosystems, especially within the Mediterranean Sea. The concern is higher for deep-sea organisms, as the Hg concentration in their tissues is commonly high. To assess the influence of food supply at two trophic levels, total Hg concentrations and carbon and nitrogen stable isotope ratios were determined in 7 species (4 teleosts, 2 sharks, and 1 crustacean) sampled on the upper part of the continental slope of the Gulf of Lions (Northwestern Mediterranean Sea), at depths between 284 and 816 m. Mean Hg concentrations ranged from 1.30±0.61 to 7.13±7.09 µg g(-1) dry mass, with maximum values observed for small-spotted catshark Scyliorhinus canicula. For all species except blue whiting Micromesistius poutassou, Hg concentrations were above the health safety limits for human consumption defined by the European Commission, with a variable proportion of the individuals exceeding limits (from 23% for the Norway lobster Nephrops norvegicus to 82% for the blackbelly rosefish Helicolenus dactylopterus). Measured concentrations increased with increasing trophic levels. Carbon isotopic ratios measured for these organisms demonstrated that settling phytoplanktonic organic matter is not only the main source fueling trophic webs but also the carrier of Hg to this habitat. Inter- and intraspecific variations of Hg concentrations revealed the importance of feeding patterns in Hg bioaccumulation. In addition, biological parameters, such as growth rate or bathymetric range explain the observed contamination trends.

Deep-sea foraminifera from the Cassidaigne Canyon (NW Mediterranean): assessing the environmental impact of bauxite red mud disposal.

Benthic foraminiferal assemblages were investigated from two sites along the axis of the Cassidaigne Canyon (NW Mediterranean Sea). Both areas are contaminated by bauxite red mud enriched in iron, titanium, vanadium and chromium. These elemental enrichments are related to bauxite-derived minerals and various amorphous phases. At the shallowest station located very close to the pipe outlet, the benthic living foraminiferal community is characterised by a very low diversity and by an unusual dominance of Gyroidina umbonata and Bulimina marginata. The mechanical stress related to downslope transport of red mud is a likely source of hydro-sedimentary pollution precluding the settlement of diverse fauna. The living and dead foraminiferal faunas from the deepest site are typical of oligo-mesotrophic conditions prevailing in natural environments. There, bauxite residues have obviously no environmental impact on foraminiferal faunas. The bioavailability of trace metals is likely low as elemental enrichments were not observed in foraminiferal test chemistry.

Combination of folinic acid, 5-fluorouracil bolus and infusion, and cisplatin (LV5FU2-P regimen) in patients with advanced gastric or gastroesophageal junction carcinoma.

BACKGROUND: Combination chemotherapy with continuous 5-fluorouracil (5-FU) and cisplatin in a monthly regimen is one of the standard treatments for advanced gastric carcinoma. This study evaluated the new LV5FU2-P regimen, designed to improve efficacy and tolerance of the 5-FU plus cisplatin combination. PATIENTS AND METHODS: Forty-three patients with advanced or metastatic gastroesophageal junction or gastric carcinoma were prospectively included in the study. They were treated every 14 days with cisplatin 50 mg/m(2) on day 2 plus folinic acid 200 mg/m(2)/day as a 2-h intravenous (i.v.) infusion on days 1 and 2, plus bolus 5-FU 400 mg/m(2)/day on days 1 and 2, plus continuous 5-FU 600 mg/m(2)/day as a 22-h i.v. infusion on days 1 and 2. Ten patients received a simplified regimen (folinic acid 40 mg/m(2) day 1 + bolus 5-FU 400 mg/m(2) day 1 + continuous 5-FU 2400 mg/m(2) on days 1 and 2 with cisplatin 50 mg/m(2) on day 2). RESULTS: All the patients were assessable for response and 42 for toxicity. One patient achieved a complete response and 15 a partial response, for an overall response rate of 37.2% [95% confidence interval (CI) 22.1% to 52.3%]. The median progression-free survival was 7.2 months (95% CI 5.4-10.9) and the overall survival was 13.3 months (95% CI 10.1-16.4). There were no treatment-related deaths. Hematological and gastrointestinal toxicities were the most common severe toxicities. CONCLUSIONS: LV5FU2-P is an active and well tolerated regimen in the treatment of advanced gastroesophageal junction or gastric carcinomas. It warrants evaluation comparatively with other active regimens.

Optimization of 5-fluorouracil (5-FU)/cisplatin combination chemotherapy with a new schedule of leucovorin, 5-FU and cisplatin (LV5FU2-P regimen) in patients with biliary tract carcinoma.

BACKGROUND: Unresectable biliary tract carcinoma (BTC) is associated with a very poor prognosis. To improve efficacy and tolerance of the 5-fluorouracil (5-FU)/cisplatin combination in BTC, we designed a new therapeutic schedule, the LV5FU2-P regimen. PATIENTS AND METHODS: Twenty-nine patients with advanced or metastatic BTC were prospectively enrolled in the study. The treatment (LV5FU2-P regimen) consisted of a biweekly administration of a 2-h infusion of leucovorin 200 mg/m(2), a 400 mg/m(2) bolus of 5-FU followed by a 22-h continuous infusion of 600 mg/m(2) 5-FU on two consecutive days and cisplatin 50 mg/m(2) on day 2. Clinical symptoms, performance and weight changes were monitored. RESULTS: Objective responses were observed in 10 patients (34%) (95% confidence interval 23% to 45%) including one complete response and nine partial responses (stabilization 38%, progression 28%). Median progression-free survival and overall survival were 6.5 and 9.5 months, respectively. Weight gain was observed in 45% of patients and performance status improved in 60%. One patient had a grade 4 thrombocytopenia, and grade 3 toxicity occurred in 41% of patients. There were no treatment-related deaths. CONCLUSIONS: This study, one of the largest phase II trials performed for this disease, shows that the LV5FU2-P regimen is an active and well-tolerated chemotherapy for advanced and metastatic BTC.

[Established data and practical recommendations concerning pre- and postoperative chemotherapy of rectal cancer]. / Acquis et recommandations pratiques en matière de chimiothérapie pré- et post-opératoire des cancers du rectum.

Adjuvant chemotherapy appears to be active in stage II-III rectal cancers; the NSAPB R01 trial demonstrated a survival advantage for patients receiving chemotherapy using the MOF protocol and 3 meta-analyses are in favor of the efficacy of adjuvant chemotherapy in rectal cancer. Three randomized trials have also demonstrated that combinations of radiation and chemotherapy are superior to surgery alone or adjuvant radiotherapy and demonstrated the major role of systemic chemotherapy combined with radiotherapy. However this efficacy of adjuvant chemotherapy alone or combined with radiation therapy is still debated and specific trials must be conducted to test the value of chemotherapy using more active regimens than those previously tested and taking into account the quality of surgery and radiotherapy; such trials are in progress, especially the trial conducted by the EORTC and the FFCD. The efficacy of neoadjuvant chemotherapy has never been clearly demonstrated, although a combination of radiotherapy and chemotherapy as first-line treatment for locally advanced rectal cancer and in the case of synchronous metastasis seems to facilitate surgical resection. It is a reasonable and tolerable approach with manageable toxicity which gives substantial results in 2/3 of patients. This strategy also allows better selection of patients likely to benefit from surgical resection of their primary tumor and in some cases of their synchronous metastases. However, the efficacy of perioperative treatments should not decrease the quality of the surgical resection and especially mesorectal excision as well as the need for high quality pathological examination which must be very thorough with analysis of a sufficient number of lymph nodes. The efficacy of combined treatment in advanced rectal cancers is a major argument in favor of the multidisciplinary coordination required for optimal treatment of patients with rectal cancer.

[Importance of a multidisciplinary approach to metastatic cancer of the rectum]. / Intérêt d'une approache multidisciplinaire des cancers du rectum initialement métastatiques.

Management of rectal cancers with synchronous metastasis is difficult. We evaluated in 23 patients a combination of pelvic radiotherapy at the dose of 45 Gy in 5 weeks and 25 fractions with chemotherapy by 5-fluorouracil (350 mg/m2/day) and folinic acid (20 mg/m2/day) for 5 days at the time of the first and the fifth week of the irradiation. Surgery was indicated firstly in cases of stricture or secondarily for resection of the primary location and, when possible, of the metastasis. General state of health of the patients improved in 35%, symptomatology in 86% and comfort in 72% of the cases. Response rates for the primary tumor were 41% of partial response and 50% of stable disease. For the metastatic lesions, they were 9% and 59% respectively. Sixty-one per cent of patients were secondarily operated with resection of the primary tumor in 12 cases and of hepatic metastases in 2 cases. The median survival and the median survival without progression were respectively 13 and 9 months. Radiochemotherapy combination as the first treatment was beneficial in 4/5 of the patients presenting a rectal cancer with synchronous metastasis and allowed us to select those that would secondarily benefit from a surgical resection.

Effective treatment of advanced biliary tract carcinoma using 5-fluorouracil continuous infusion with cisplatin.

BACKGROUND: The combination of 5-fluorouracil (5-FU) and cisplatin has shown great activity in many different types of tumour with an in vitro synergistic effect between 5-FU and cisplatin. A phase II study of 5-FU plus cisplatin was performed in 25 previously untreated patients with inoperable locally advanced or metastatic biliary tract carcinoma. PATIENTS AND METHODS: Twenty-five patients, 10 of them men and 15 women with a median age of 58, were entered into the study. The chemotherapy regimen consisted of 5-FU: 1 g/m2/day in continuous intravenous (i.v.) infusion for five consecutive days, and cisplatin: 100 mg/m2/day on day 2 in a one-hour infusion with standard hyperhydration. Twenty-two patients had metastatic tumours and three had locally advanced disease. RESULTS: Of the 25 patients entered into the study, 24 were evaluable for response and 25 for toxicity. Nausea and vomiting was the main toxic side effect in 19 patients. Severe, WHO grade 3-4 thrombocytopenia or neutropenia were observed in three and seven patients, respectively. There were no toxic deaths. Of 25 patients, six had partial remissions (overall response 24%, 95% confidence interval 7%-41%). For three patients, tumour reduction permitted local radiotherapy and one of these patients with initially advanced disease is still alive six years after the beginning of treatment. CONCLUSIONS: This study, one of the largest phase II trials performed in this disease, shows interesting activity of the combination of 5-FU and cisplatin in advanced biliary tract carcinoma.

5-Fluorouracil (5-FU) continuous intravenous infusion compared with bolus administration. Final results of a randomised trial in metastatic colorectal cancer.

The aim of this Phase III, balanced randomised trial was to compare continuous intravenous infusion (CVI) of 5-FU with bolus (B) administration for metastatic colorectal cancer (CRC). One hundred and fifty-five non-pretreated patients were randomised to receive CVI 5-FU at a dose of 750 mg/m2/day (d), 7 d every 21 d (n = 77), or bolus 5-FU 500 mg/m2/d x 5 d every 28 d (n = 78). Incremental dose escalation at 50 mg per step was recommended in the absence of toxicity. All the patients had measurable metastatic disease (M), particularly, liver and a good performance status (WHO grade 0-1). Dose intensity was significantly higher in CVI than in the bolus group: 1369 mg/m2/week versus 558 mg/m2/week (P = 0.0001). Grade II-IV stomatitis was more frequent in the CVI group (31% versus 9%; P < 0.0001) as was hand and foot syndrome (14% versus 3%; P < 0.001). Diarrhoea (22% versus 12%) and grade III granulocytopenia (2% versus 6%) were comparable. Responses were more frequent in the CVI (26%) than in the bolus group (13%) (P < 0.04); progression-free survival was higher for the CVI group (P = 0.04), but there was no statistical difference in overall survival (median: 10 months (m) compared to 9 m), and 1 year survival (SD) 42% (6%) versus 40% (6%). In the multivariate analysis, survival was better for patients with a good PS, well-differentiated adenocarcinomas and a primary tumour without serosal extension. In conclusion, with a higher dose intensity, CVI 5-FU improved tumour control, but not overall survival.

Fotemustine in patients with advanced gastric cancer, a phase II trial from the EORTC-GITCCG (European Organization for Research and Treatment of Cancer, Gastrointestinal Tract Cancer Cooperative Group).

Fotemustine activity was evaluated in 26 patients, mostly pretreated, with advanced gastric cancer. Its main toxicity was haematological with grade 3-4 neutropenia in 32% and grade 3-4 thrombocytopenia in 50% of the patients, complicated by 2 toxicity-related deaths due to haemorrhage. No complete or partial responses were observed in the 26 eligible patients and median survival was only 11 weeks. Fotemustine therefore has no activity in advanced gastric cancer.

[Treatment of hepatocellular carcinoma in the presence of liver cirrhosis]. / Traitement du carcinome hépatocellulaire sur cirrhose.

Hepatocellular carcinoma accounts for 90% of the primary malignant liver tumours. Most cases occur in cirrhotic livers. Management decisions should not be based on the stage of the tumour extension but rather on the functional situation of the liver. The first therapeutic option which should be considered is surgical resection if the case presents with a single tumour (or less than 4 tumours for some teams) without detectable metastasis nor intraportal thrombosis and if the liver remaining after surgery will be sufficient for normal hepatic functions. The disadvantage of resection is the high risk of recurrence in the long term. Liver transplantation cannot be proposed if the hepatocellular carcinoma has produced clinical signs but it can be a possibility in case of a resectable tumour in the framework of a prospective protocol comparing transplantation and resection. Intra-arterial injection of 131-iodine linked lipiodol is the only effective treatment in case of portal thrombosis. Chemoembolization of nonresectable hepatocellular carcinoma has led to spectacular tumour response but its effect on survival has not been demonstrated by randomized studies. For tumours less than 3 cm in diameter, even multifocal alcoholization has proved encouraging results. Although a randomized study of questionable quality suggested tamoxifen could be effective, there is no current indication for this drug. External radiotherapy may be a possibility in the future, especially with proton irradiation. Thus the current management of hepatocellular carcinoma is in a difficult, even paradoxical, situation since there is a wide therapeutic choice (resection, alcoholization, transplantation) for the rare cases with small tumours but almost no possibilities for the more severe cases most frequently encountered.

Determination of the optimal dose of 5-fluorouracil when combined with low dose D,L-leucovorin and irradiation in rectal cancer: results of three consecutive phase II studies. EORTC Radiotherapy Group.

In three consecutive phase II trials, 5-fluorouracil (5FU)-low dose leucovorin (20 mg/m2/day) was delivered in two 5-day courses during the first (d1 to d5) and the last (d29 to d33) week of a limited pelvic irradiation (45 Gy, 5 weeks, 25 fractions) in patients with locally extended rectal cancer. The three trials differed only by the 5FU dose in the chemotherapy (CT) schemes. In trial 1 (first CT course 5FU dose 425 mg/m2/day, second CT course 370 mg/m2/day), 16 patients were included. 5 patients suffered a grade 3+ toxicity and the compliance was 63%. In trial 2 (first and second CT course 5FU dose 370 mg/m2/day), 53 patients were included. 5 patients suffered a grade 3+ toxicity. The compliance was 94%. In the trial 3 (first and second CT course 5FU dose 350 mg/m2/day), 16 patients were included. 1 patient suffered a grade 3 toxicity and the compliance was 100%. The overall response rate (complete and partial responses) of local disease and distant metastasis were 87 and 7%, respectively. 43 patients were operated on after a mean delay of 8 weeks. Among the 41 macroscopic complete resections, 6 (14.6%) were sterilised and 12 (29.3%) were classified Asler-Coller A/B1. Regression curve analysis using either grade 3+ toxicity or incomplete treatment as an end point against the 5FU dose indicates that a 350 mg/m2/day 5FU dose is advisable for a phase III adjuvant multicentre trial.

[Chemical mapping of normal and tumorous gastric mucosa by analytical ion microscopy]. / Imagerie chimique de la muqueuse gastrique normale et tumorale, obtenue par microscopie ionique analytique.

The analytical ion microscopy (AIM) makes possible quantitative mapping of chemical elements on tissue section this method was applied to the study of chlorine (Cl-) and sulfur (S-) distributions on chemically fixed stomach sections obtained by biopsy. The Cl- and S- images were correlated with the histological structure of the tissue obtained by the phosphorus distribution on the same field or by the photonic image of a serial section. In normal tissue, Cl- and S- were evidenced in cytoplasm with accumulation at the apical cell border while in gastric adenocarcinoma both elements were distributed without precise topography. The use of cryo-prepared specimens should offer the possibility to study the changes of chlorine and sulfur content in functional pathology of stomach.

[Hodgkin's disease disclosed by myelofibrosis of primary appearance. Apropos of 2 cases]. / Maladie de Hodgkin révélée par une myélofibrose en apparence primitive. A propos de deux observations.

Two male patients, aged 36 and 73 years respectively, gradually developed febrile pancytopenia with profound alteration of their general condition and major inflammatory repercussions. No superficial or deep lymph node enlargement was found initially. Patient n degree 2 had an enlarged spleen. In both cases histological examination of the bone marrow showed an extensive and apparently nonspecific myelofibrosis. The subsequent development of superficial lymphadenopathy provided a firm diagnosis of Hodgkin's disease with mixed cellularity. These two cases belong to the category of exceptional massive medullary forms of Hodgkin's disease described by Duhamel et al. in 1979.