Anthropogenic eutrophication of Lake Titicaca (Bolivia) revealed by carbon and nitrogen stable isotopes fingerprinting.

Cultural eutrophication is the leading cause of water quality degradation worldwide. The traditional monitoring of eutrophication is time-consuming and not integrative in space and time. Here, we examined the use of carbon (δ13C) and nitrogen (δ15N) isotopic composition to track the degree of eutrophication in a bay of Lake Titicaca impacted by anthropogenic (urban, industrial and agricultural wastewater) discharges. Our results show increasing δ13C and decreasing δ15N signatures in macrophytes and suspended particulate matter with distance to the wastewater source. In contrast to δ15N and δ13C signatures, in-between aquatic plants distributed along the slope were not only affected by anthropogenic discharges but also by the pathway of carbon uptake, i.e., atmospheric (emerged) vs aquatic (submerged). A binary mixing model elaborated from pristine and anthropogenic isotope end-members allowed the assessment of anthropogenically derived C and N incorporation in macrophytes with distance to the source. Higher anthropogenic contribution was observed during the wet season, attributed to enhanced wastewater discharges and leaching of agricultural areas. For both seasons, eutrophication was however found naturally attenuated within 6 to 8 km from the wastewater source. Here, we confirm that carbon and nitrogen stable isotopes are simple, integrative and time-saving tools to evaluate the degree of eutrophication (seasonally or annually) in anthropogenically impacted aquatic ecosystems.

Diagenetic production, accumulation and sediment-water exchanges of methylmercury in contrasted sediment facies of Lake Titicaca (Bolivia).

Monomethylmercury (MMHg) concentrations in aquatic biota from Lake Titicaca are elevated although the mercury (Hg) contamination level of the lake is low. The contribution of sediments to the lake MMHg pool remained however unclear. In this work, seven cores representative of the contrasted sediments and aquatic ecotopes of Lake Titicaca were sliced and analyzed for Hg and redox-sensitive elements (Mn, Fe, N and S) speciation in pore-water (PW) and sediment to document early diagenetic processes responsible for MMHg production and accumulation in PW during organic matter (OM) oxidation. The highest MMHg concentrations (up to 12.2 ng L-1 and 90% of THg) were found in subsurface PWs of the carbonate-rich sediments which cover 75% of the small basin and 20% of the large one. In other sediment facies, the larger content of OM restricted MMHg production and accumulation in PW by sequestering Hg in the solid phase and potentially also by decreasing its bioavailability in the PW. Diagenetically reduced S and Fe played a dual role either favoring or restricting the availability of Hg for biomethylation. The calculation of theoretical diffusive fluxes suggests that Lake Titicaca bottom sediments are a net source of MMHg, accounting for more than one third of the daily MMHg accumulated in the water column of the Lago Menor. We suggest that in the context of rising anthropogenic pressure, the enhancement of eutrophication in high altitude Altiplano lakes may increase these MMHg effluxes into the water column and favor its accumulation in water and biota.

Mercury contamination level and speciation inventory in Lakes Titicaca & Uru-Uru (Bolivia): Current status and future trends.

Aquatic ecosystems of the Bolivian Altiplano (∼3800 m a.s.l.) are characterized by extreme hydro-climatic constrains (e.g., high UV-radiations and low oxygen) and are under the pressure of increasing anthropogenic activities, unregulated mining, agricultural and urban development. We report here a complete inventory of mercury (Hg) levels and speciation in the water column, atmosphere, sediment and key sentinel organisms (i.e., plankton, fish and birds) of two endorheic Lakes of the same watershed differing with respect to their size, eutrophication and contamination levels. Total Hg (THg) and monomethylmercury (MMHg) concentrations in filtered water and sediment of Lake Titicaca are in the lowest range of reported levels in other large lakes worldwide. Downstream, Hg levels are 3-10 times higher in the shallow eutrophic Lake Uru-Uru than in Lake Titicaca due to high Hg inputs from the surrounding mining region. High percentages of MMHg were found in the filtered and unfiltered water rising up from <1 to ∼50% THg from the oligo/hetero-trophic Lake Titicaca to the eutrophic Lake Uru-Uru. Such high %MMHg is explained by a high in situ MMHg production in relation to the sulfate rich substrate, the low oxygen levels of the water column, and the stabilization of MMHg due to abundant ligands present in these alkaline waters. Differences in MMHg concentrations in water and sediments compartments between Lake Titicaca and Uru-Uru were found to mirror the offset in MMHg levels that also exist in their respective food webs. This suggests that in situ MMHg baseline production is likely the main factor controlling MMHg levels in fish species consumed by the local population. Finally, the increase of anthropogenic pressure in Lake Titicaca may probably enhance eutrophication processes which favor MMHg production and thus accumulation in water and biota.

Synergistic effects of mining and urban effluents on the level and distribution of methylmercury in a shallow aquatic ecosystem of the Bolivian Altiplano.

Lake Uru Uru (3686 m a.s.l.) located in the Bolivian Altiplano region receives both mining effluents and urban wastewater discharges originating from the surrounding local cities which are under rapid development. We followed the spatiotemporal distribution of different mercury (Hg) compounds and other metal(oid)s (e.g., Fe, Mn, Sb, Ti and W) in both water and sediments during the wet and dry seasons along a north-south transect of this shallow lake system. Along the transect, the highest Hg and metal(oid) concentrations in both water and sediments were found downstream of the confluences with mining effluents. Although a dilution effect was found for major elements during the wet season, mean Hg and metal(oid) concentrations did not significantly differ from the dry season due to the increase in acid mine drainage (AMD) inputs into the lake from upstream mining areas. In particular, high filtered (<0.45 µm) mono-methylmercury (MMHg) concentrations (0.69 ± 0.47 ng L-1) were measured in surface water representing 49 ± 11% of the total filtered Hg concentrations (THgF) for both seasons. Enhanced MMHg lability in relation with the water alkalinity, coupled with abundant organic ligands and colloids (especially for downstream mining effluents), are likely factors favoring Hg methylation and MMHg preservation while inhibiting MMHg photodegradation. Lake sediments were identified as the major source of MMHg for the shallow water column. During the dry season, diffusive fluxes were estimated to be 227 ng m-2 d-1 for MMHg. This contribution was found to be negligible during the wet season due to a probable shift of the redox front downwards in the sediments. During the wet season, the results obtained suggest that various sources such as mining effluents and benthic or macrophytic biofilms significantly contribute to MMHg inputs in the water column. This work demonstrates the seasonally dependent synergistic effect of AMD and urban effluents on the shallow, productive and evaporative high altitude lake ecosystems which promotes the formation of natural organometallic toxins such as MMHg in the water column.

Diurnal variability and biogeochemical reactivity of mercury species in an extreme high-altitude lake ecosystem of the Bolivian Altiplano.

Methylation and demethylation represent major transformation pathways regulating the net production of methylmercury (MMHg). Very few studies have documented Hg reactivity and transformation in extreme high-altitude lake ecosystems. Mercury (Hg) species concentrations (IHg, MMHg, Hg°, and DMHg) and in situ Hg methylation (M) and MMHg demethylation (D) potentials were determined in water, sediment, floating organic aggregates, and periphyton compartments of a shallow productive Lake of the Bolivian Altiplano (Uru Uru Lake, 3686 m). Samples were collected during late dry season (October 2010) and late wet season (May 2011) at a north (NS) and a south (SS) site of the lake, respectively. Mercury species concentrations exhibited significant diurnal variability as influenced by the strong diurnal biogeochemical gradients. Particularly high methylated mercury concentrations (0.2 to 4.5 ng L(-1) for MMHgT) were determined in the water column evidencing important Hg methylation in this ecosystem. Methylation and D potentials range were, respectively, <0.1-16.5 and <0.2-68.3 % day(-1) and were highly variable among compartments of the lake, but always higher during the dry season. Net Hg M indicates that the influence of urban and mining effluent (NS) promotes MMHg production in both water (up to 0.45 ng MMHg L(-1) day(-1)) and sediment compartments (2.0 to 19.7 ng MMHg g(-1) day(-1)). While the sediment compartment appears to represent a major source of MMHg in this shallow ecosystem, floating organic aggregates (dry season, SS) and Totora's periphyton (wet season, NS) were found to act as a significant source (5.8 ng MMHg g(-1) day(-1)) and a sink (-2.1 ng MMHg g(-1) day(-1)) of MMHg, respectively. This work demonstrates that high-altitude productive lake ecosystems can promote MMHg formation in various compartments supporting recent observations of high Hg contents in fish and water birds.

Induction chemotherapy in advanced head and neck tumors: results of two randomized trials.

From March 1983 to December 1989, 208 patients with locally advanced squamous cell carcinoma of the head and neck were successively included into two randomized induction chemotherapy trials. The chemotherapy regimen of the first trial, which included 100 patients, consisted of two cycles of a combination of cisplatin, bleomycin, vindesine and mitomycin C; while that of the second trial, which included 108 patients, consisted of three cycles of a combination cisplatin, 5-fluorouracil by continuous infusion and vindesine. Local treatment was the same in the two trials: primary radiotherapy in all patients. The response was then evaluated; in the case of a poor response at 55 Grays surgery was performed; otherwise, radiotherapy was continued to full doses (possibly followed by salvage surgery). The tumor and lymph node responses to chemotherapy (complete and partial response) were higher in the second trial than in the first: 70% versus 50% for primary lesions, 47% versus 25% for lymph nodes. The toxicity of the two chemotherapy regimens was minimal. In the two trials, an initial major response to chemotherapy predicted subsequent efficacy of irradiation in 80% of the patients. The significance of the complete response at the end of the irradiation varies with the previous response to the chemotherapy. With a median follow-up of 60 months with the first chemotherapy regimen and 30 months with the second, overall survival and disease-free interval were very similar in the two groups. The incidence of distant metastasis was significantly reduced (p less than 0.03) with chemotherapy. This trial suggests the need to test new chemotherapy protocols according to new schemes of treatment, with chemotherapy given concurrently with or following the completion of standard treatment by means of multicenter randomized trials.

Prognostic value of tumor regression during radiotherapy for head and neck cancer: a prospective study.

OBJECTIVE: Prospective evaluation of tumor regression during external irradiation for head and neck squamous cell carcinomas and its association with long-term local control. METHODS AND MATERIALS: Two hundred twenty-eight patients with histologically confirmed squamous cell carcinoma [oral cavity: 59 (26%), oropharynx: 65 (29%), hypopharynx: 37 (16%), larynx: 67 (29%)] were included between January 1986 and December 1990. Curative intent external irradiation delivered 65-70 Gy over a period of 7 weeks (five 2 Gy fractions per week). Tumor regression was evaluated clinically and endoscopically every week. RESULTS: Tumor regression, assessed at 2 weeks, was as follows: no response: 62 (30%), 25% response: 121 (59%); 50% response: 23 (11%). At 5 weeks, 9 (4%) patients showed 0-25% regression, 75 (33%) showed 50% regression, 115 (50%) showed 75% regression, and 29 (13%) showed complete regression. Median follow-up was 79 months (range: 6-96 months). The local control probability was 68% (62-74%) at 2 years, 65% (59-70%) at 5 years. Univariate analysis showed that, at 2 weeks, local control was significantly different between the nonresponders and the patients with 25% or greater response (p < 0.025) and that, at the fifth week, local control was very different between the major responders (75 and 100%) and the minor responders (0-50%) (p < 0.0001). Multivariate analysis (Cox Proportional Hazards Model) showed that the probability of local relapse was significantly and independently increased for minor regression at 5 weeks [Relative risk (RR) of failure was 2.3 (1.4-3.7)], for nonlaryngeal tumors [RR: 2.4 (1.3-4.5)], and for Stage T3-T4 [RR:2.4 (1.4-4)]. Three prognostic groups can, therefore, be proposed: 1) low risk of recurrence when regression > or = 75% and laryngeal tumor or T1-T2 tumors in other sites: 106 (46.5%) patients, 2-year local control probability: 84% (77-92%); 2) high risk of recurrence: regression < or = 50% and T3-T4 nonlaryngeal tumors: 44 (19%) patients, 2-year local control probability: 27% (13-41%); 3) intermediate risk of recurrence: 78 (34.5%) patients, 2-year local control probability: 69% (58-80%). CONCLUSION: The present study suggests that tumor regression during external radiotherapy is an independent predictive factor of local control in head and neck carcinomas.

Alcohol and tobacco consumption in cancer of the mouth, pharynx, and larynx: a study of 316 female patients.

Three hundred sixteen female patients with cancer of the larynx, pharynx, and mouth were examined and the following cancer sites were compared with respect to alcohol and tobacco consumption: oropharynx, hypopharynx, larynx, epilarynx, lip, and mouth. The mean daily tobacco consumption of smokers and ex-smokers was not significantly different between cancer locations; however, significant differences between cancer sites were observed with regard to the proportion of nonsmokers. The percentage of nonsmokers was the highest for cancer of the lips and the lowest for cancer of the epilarynx. Cancer locations differed significantly depending on daily alcohol consumption. Consumption was the lowest for patients with cancer of the lips. The percentage of nondrinkers was high for cancers of the lips and larynx and low for cancer of the epilarynx. Examination of the nonsmoking/nondrinking females (27.2%) did not reveal any features specific to this group, except that the patients were older.

[Development of pharyngo-laryngeal surgery after radiotherapy]. / Evolution de la chirurgie pharyngo-laryngée après radiothérapie.

Myo-cutaneous pedicled flap (MCF) had transformed technics and indications for salvage procedures after high doses of radiotherapy in laryngeal and hypopharyngeal carcinomas. Wide field total laryngectomies extended to oropharynx, skin, circular pharyngectomies extended to cervical oesophagus are possible with 3 times less carotid blow-up and rare fistulas. Radical neck dissection is currently performed in the same procedure without major healing problems. The feeding tube is often removed within a month. Systematic use of MCF in patients irradiated over 70 Gy may reduce the post-operative mortality and yield better survival rates, which at present 2 years after salvage surgery, are 36% in hypopharyngeal carcinomas (38/106) and 50% in laryngeal cancers (106/210).

[Role of neoadjuvant chemotherapy in the treatment of advanced head and neck tumors. Results of two randomized therapeutical trials conducted at the Institut Curie on 208 patients]. / Place de la chimiothérapie néoadjuvante dans le traitement des tumeurs avancées de la tête et du cou. Résultats de deux essais thérapeutiques randomisés effectués à l'Institut Curie sur 208 patients.

From March 1983 to December 1989, 208 patients with locally advanced squamous cell carcinoma of the head and neck were successively included into two trials randomizing induction chemotherapy versus no pre-irradiation treatment. The chemotherapy regimen of the first trial, which included 100 patients, consisted of two cycles of a combination of cisplatin, bleomycin, vindesine, mitomycin C; while that of the second trial, which included 108 patients, consisted of three cycles of a combination cisplatin, 5-fluorouracil (continuous infusion) and vindesine. Local treatment was the same in two trials: 'primary' radiotherapy in all patients. The response was then evaluated at 55 Gy; in the case of poor response, surgery was performed, otherwise radiotherapy was continued to full doses (possibly followed by salvage surgery). The tumor and lymph node responses to chemotherapy (complete and partial response) were higher in the second trial and in the first one: 70% versus 50% for primary lesions, 47% versus 25% for lymph nodes. The toxicity of the two chemotherapy regimens was minimal. In the two trials, an initial major response to chemotherapy predicted subsequent efficacy of irradiation in 80% of the patients. Complete response rate at the end of irradiation correlates with the previous response to the chemotherapy. With a median follow-up of 60 months with the first chemotherapy regimen and 30 months with the second, overall survival and disease-free interval did not significantly differ in the two groups of patients, with or without chemotherapy. The incidence of distant metastasis was significantly reduced (P < 0.03) in the chemotherapy arms. This negative trial encourages the design of new chemotherapy protocols according to new schemes of treatment. For advanced stages of head and neck cancers (T3, T4, N2, N3), we recently launched a pilot study combining platinum and irradiation, but according to a concomitant schedule.

Antioxidant activity of some ascorbic and cinnamic acids derivatives.

Some 4-benzoyl 3-hydroxy furan-2 (5H) ones (3a-d) and 2-amino 3-hydroxymethyl 4-aryl 4-oxo 2-butenoic acids (4a-h) have been synthesized. Compound 3c with an isobutyl substituent in the 5-position of the furan ring was the most effective (IC50 = 8.69 x 10(-4) M) in scavenging the superoxide anion. In vivo, 3c was also protective against reperfusion injury.

[Total glossectomy without laryngectomy for recurrence after initial irradiation (2 year follow-up)]. / Glossectomies totales sans laryngectomie pour récidive après irradiation première (bilan de deux années).

In our experience of 171 glossectomies for recurrence, salvage partial glossectomy yields 50% of local control. Myo-cutaneous flap allows wide total glossectomy without total laryngectomy. This procedure may improve the local control. Of 25 patients treated by this technique, 2 deceased before the 45th post-operative day, 15 swallow correctly and 11 have a good speech. The survival rate is 10/21 at 6 months, 7/16 at 12 and 6/13 at 18. A local failure was observed in 7 and 6 have a second primary in the upper respiratory and digestive tract. Total glossectomy without total laryngectomy is only indicated for patients with bulky tumor, without spread of the vallecula and with no palpable cervical node.

[Cancers of the soft palate. Results of repeat surgery]. / Cancers du voile du palais. Résultats de la chirurgie de rattrapage.

Between 1960 and 1983, 270 patients were treated at the CURIE Institute for a carcinoma of the soft palate, including 260 by radiotherapy (mean dose: 69 Gy). Most of these tumours were T1 T2 (201 cases, 76%). There was a high frequency of a past history of carcinoma (38 cases, 14%) as well as of simultaneous carcinomas (44 cases, 16%). Two months after radiotherapy, a velar tumor persisted in 29 patients whilst 1 patient had deep necrosis. 15 of these 30 patients underwent secondary surgical excision. This surgical series included 25 of 27 recurrences seen secondarily and 6 patients operated on for second velar carcinoma appearing in the irradiated zone (mean dose: 68 Gy). 45 of the 46 excisions were carried out by a buccal approach. Overall survival after surgery was 32% at 3 years. The 11 patients operated on for an extensive T3 T4 tumour died before 12 months. These poor results were related to the frequency of local recurrences (12 loco-regional failures amongst 36 deaths) as well as the number of deaths due to second carcinomas (11 deaths amongst the surgical patients). Later carcinomas were particularly frequent during the course of tumours of this site (69 cases out of 270), the problem of multiple malignant tumours finally affecting 122 patients out of 270, i.e. 45%.

[Results of operations of salvage laryngectomy]. / Résultats des interventions de laryngectomie de rattrapage.

The surgery of the larynx in an irradiated neck changed since 30 years by an evolution of the radiotherapeutic technics and the surgical procedures. At the Curie Institute, from 1960 to 1986, 230 patients were operated with laryngectomy for failure of the first treatment (average doses: 70 Gy). 29 had partial laryngectomy. The feeding tube was removed before 6 weeks in 78% of the patients. 19 patients (8%) died in the 3 months after surgery (8 carotid blow-up). The crude survival rates are 70% at 1 yr, 42% at 3 tr, 37% at 5 yr. These rates are identical in patients with persistent disease two months after irradiation (90), in patients with recurrence (110) and for those with second primary in the larynx (21). 54% of T1 and T2 patients are NED at 3 yr and 47% at 5 yr. For T3 and T4 rates are only 22% and 17%. Best results are in glottic cancers (74% at 3 yr); poorest in advanced supra-glottic (17%). Salvage procedure is effective in larynx and neck in 62% of the patients. Early detection of a failure after irradiation is a major condition for the application of a protocol of definitive radiotherapy in laryngeal cancer.

[Cancers of the hypopharynx. Course of surgical salvage]. / Cancers de l'hypopharynx. Evolution du rattrapage chirurgical.

Recovery surgery on irradiated hypopharyngeal zones, and the indications for this operation, have been transformed by currently available possibilities for pharyngeal reconstruction and protection of carotid axis by musculocutaneous pedicle flaps. Of 117 patients operated upon in the Curie Institute between 1960 and 1986 for hypopharyngeal cancer, after radiotherapy (mean dose 70 Gy), deglutition was restored in 100 cases (85%) after a mean healing period of 30 days. Fatal postoperative complications occurred in 23 patients (19%), including 12 carotid hemorrhages, but since 1980 the percentage of mortal bleeding has dropped from 15 to 5%. Postoperative survival was 50% at 1 year, 29% at 3 years and 15% at 5 years, results being similar whatever the indication (46 patients operated upon at end of radiotherapy, 36 local recurrences and 37 second cancers in irradiated zone). Local and regional recovery surgery was effective in only one patient out of two. The musculocutaneous flap allows wider and more certain surgery and improved functional results, but in no way affects the particularly serious nature of cancer of this localization.

[Reconstruction surgery and repair using a musculocutaneous flap. Apropos of 124 cases]. / Chirurgie de rattrapage et réparation par lambeau myo-cutané. A propos de 124 cas.

Between 1981 and 1983, 116 patients (109 men and 7 women) underwent reconstructive surgery with musculocutaneous flaps following major surgical excision of a cervicofacial tumor recurring after curative radiotherapy. Mean age of patients was 54 years. The most frequently used flap (110/124) was from the pectoralis major. Advantages of the use of a musculocutaneous flap for repair appear to be: first intention healing in most cases; notable reduction in hospital stay; possibility of wider tumoral excision and also of combining lymph node excision, and improved functional results. Follow-up surveillance has been for a mean of only one year, too short a period for assessing carcinologic results.

[Management of laryngeal cancers]. / Particularités des cancers du larynx.

With 5,000 cases yearly, laryngeal carcinomas account in France for the third of squamous cell cancers of the upper digestive and respiratory tract. The crude survival rate is 50% at 5 years. Carcinomas of vocal cords are often diagnosed as early stages if dysphonia leads the patients to the ENT specialist within 2 weeks. Cure of the primary is achieved in 90% of the early stages by radiotherapy with narrow fields or partial surgery, with a 80% 5 years survival rate. Advanced tumors are often treated by total laryngectomy and postoperative radiotherapy. Supra-glottic cancers (epiglottis) are more serious. Unilateral dysphagia or upper cervical neck node often delay early diagnosis. A total laryngectomy is the commonest treatment. The 5 years survival rate of 40% is due to local and/or regional failures and metachronous cancers in head and neck, and radiotherapy remains the two major treatments. Primary prevention is based upon suppression of tobacco and reduction of alcoholic consumption, secondary prevention on resection of leucoplakia and close follow-up of patients with chronic laryngitis.