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.

Multielemental speciation of trace elements in estuarine waters with automated on-site UV photolysis and resin chelation coupled to inductively coupled plasma mass spectrometry.

An integrated approach for the accurate determination of total, labile and organically bound dissolved trace metal concentration in the field is presented. Two independent automated platforms consisting of an ultraviolet (UV) on-line unit and a chelation/preconcentration/matrix elimination module were specifically developed to process samples on-site to avoid sample storage prior to inductively coupled plasma mass spectrometry (ICP-MS) analysis. The speciation scheme allowed simultaneous discrimination between labile and organic stable dissolved species of seven trace elements including Cd, Cu, Mn, Ni, Pb, U and Zn, using only 5ml of sample with detection limits ranging between 0.6ngl(-1) for Cd and 33ngl(-1) for Ni. The influence of UV photolysis on organic matter and its associated metal complexes was investigated by fluorescence spectroscopy and validated against natural samples spiked with humic substances standards. The chelation/preconcentration/matrix elimination procedure was validated against an artificial seawater spiked sample and two certified reference materials (SLRS-4 and CASS-4) to ensure homogenous performance across freshwater, estuarine and seawater samples. The speciation scheme was applied to two natural freshwater and seawater samples collected in the Adour Estuary (Southwestern, France) and processed in the field. The results indicated that the organic complexation levels were high and unchanged for Cu in both samples, whereas different signatures were observed for Cd, Mn, Ni, Pb, U and Zn, suggesting organic ligands of different origin and/or their transformation/alteration along estuarine water mixing.

Cancer of the base of the tongue: past and future.

BACKGROUND: Squamous cell carcinomas of the base of the tongue often are diagnosed at advanced stages, in a context of undernutrition with a history of smoking and alcoholism. The local treatment of these tumours is based on external irradiation, either alone or combined with brachytherapy, followed by salvage surgery in the case of failure. Surgery was rarely performed as first-line treatment in our institution until 1992. METHODS: From 1960 to 1992, 216 patients were treated, without prior selection, according to the same protocol comprising external irradiation and salvage surgery in the case of failure. The tumour classification (UICC 88) was as follows: 14% of T1, 26% of T2, 44% of T3; 16% of T4; the median age was 58 years; tumour regression was evaluated during and at the end of irradiation. RESULTS: The locoregional control rates were 45% at 5 years, 37% at 10 years: 82% at 5 and 10 years for stage I, 65% and 54% for stage II, 51% and 45% for stage III, 35% and 32% for stage IV. Overall survival rates were 27% at 5 years and 14% at 10 years; 53% and 27% for stage I, 34% and 17% for stages II and III, 18% and 12% for stage IV. Causes of death were primarily local failures (58%), intercurrent disease (15%), metastases (10%), and second cancers (8%). Multivariate analysis demonstrated three predictive factors of locoregional control and survival: tumour regression at the end of irradiation (p = 0.0001), age (p = 0.04), and tumour stage (p = 0.06). CONCLUSION: The results of this retrospective series confirm the poor prognosis of tumours of the base of the tongue. Irradiation and surgery remain the standard treatments; possibilities of improvement are currently under evaluation, such as acceleration of irradiation, and concomitant radiochemotherapy combinations, which currently appear to be the most promising approaches.

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.

Soluble interleukin-2 receptor serum level as a predictor of locoregional control and survival for patients with head and neck carcinoma: results of a multivariate prospective study.

BACKGROUND: The diagnosis and follow-up of head and neck carcinoma patients are based exclusively on clinical staging, which cannot always predict clinical outcome accurately. Because oral squamous cell carcinomas produce interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha and express IL-2 receptors, the authors assessed the prognostic value of the serum levels of these markers. METHODS: Serum levels of IL-6, TNF-alpha, soluble IL-2 receptors (s-IL-2-R), and acute phase proteins were measured at the time of diagnosis in a prospective study of 85 patients with primary squamous cell carcinoma of the head and neck. The influence of each clinical and laboratory parameter on locoregional control and survival was analyzed. RESULTS: At presentation, a relationship was observed between advanced tumor (T) classification and high serum levels of CRP (P = 0.0015) and s-IL-2-R (P < 0.05). A high lymph node (N) classification was significantly associated with elevated serum IL-6 (P = 0.01) and CRP levels (P = 0.0002). In the univariate analysis, T classification, N classification, performance status, Prognostic Inflammatory and Nutritional Index, and serum s-IL-2-R level were significantly correlated with both locoregional control and survival. Multivariate analysis showed that the only significant prognostic factors related independently to locoregional control were N classification (P = 0.02) and serum s-IL-2-R level (P = 0.02). In a Cox multivariate analysis, serum s-IL-2-R level was found to be the most predictive factor of survival (P = 0.0001). CONCLUSIONS: This study shows that serum s-IL-2-R level at the time of diagnosis represents a new independent prognostic variable for predicting the risk of locoregional recurrence and survival for patients with head and neck squamous cell carcinoma.

Anemia is associated with lower local-regional control and survival after radiation therapy for head and neck cancer: a prospective study.

PURPOSE: To evaluate the prognostic value of anemia in squamous cell carcinomas in the head and neck treated with curative radiation therapy alone. MATERIALS AND METHODS: In a prospective study, the hemoglobin level was measured prior to radiation therapy in 217 patients (188 [87%] men and 29 [13%] women) with cancer of the oral cavity (n = 61 [28%]), oropharynx (n = 53 [24%]), hypopharynx (n = 21 [10%]), and larynx (n = 82 [38%]). Anemia, defined as hemoglobin level below 13.5 g/dL in men and below 12.0 g/dL in women, was diagnosed in 58 (31%) of the men and five (17%) of the women. Median follow-up was 29 months (range, 2-63 months). RESULTS: The 2-year actuarial probability of local-regional control was 69% (95% confidence interval, 63%, 76%). Multivariate analysis showed the relative risk of failure of local-regional control to increase for stage T3 and T4 tumors (1.8 [95% confidence interval, 1.1, 3.1]), stage N3 nodes (3.6 [95% confidence interval, 1.8, 7.1]), weight loss (2.2 [95% confidence interval, 1.3, 4.0]), and anemia (1.6 [95% confidence interval, 1.0-2.7]). The relative risk of death increased for stage T3 and T4 tumors (2.5 [95% confidence interval, 1.4, 4.3]), N3 nodes (4.0 [95% confidence interval, 1.0, 7.9]), oral cavity tumors (2.0 [95% confidence interval, 1.2, 3.2]), male sex (4.1 [95% confidence interval, 1.3, 13.1]), weight loss (2.2 [95% confidence interval, 1.3, 3.7]), and anemia (1.7 [95% confidence interval, 1.03, 2.7]). CONCLUSION: Moderate anemia appeared to be an independent prognostic factor in squamous cell carcinoma of the head and neck treated with radiation therapy alone.

[Surgery of the oropharynx after radiotherapy]. / Chirurgie de l'oropharynx après radiothérapie.

Over 40 years after the first commando procedures performed by M Dargent, surgical techniques such as mandibulotomy and myocutaneous flaps yield important changes in oropharyngeal surgery after definitive radiotherapy. Wide resections and simultaneous neck dissection are possible with good functional results. From 1970 to 1990, 250 patients with a carcinoma of the oropharynx were operated on after radiotherapy, 163 because of failure or complication of irradiation, 87 for a metachronous carcinoma occurred in an previously irradiated field. The postoperative mortality rate was 6%. The risk of carotid blow-up did not increase with the extension of the resection. Survival rates at 1, 3 and 5 years are 55%, 22%, 16% in salvage surgery and 69%, 36% and 24% in patients with metachronous cancer. Postoperative complications and failures in the primary and/or the neck account for 60% of causes of death. These results suggest that prior surgery of deeply ulcerative carcinoma of the oropharynx followed by radiotherapy is a better strategy than definitive radiotherapy with salvage surgery in reserve.

[Surgery of the hypopharynx after radiotherapy]. / Chirurgie de l'hypopharynx après radiothérapie.

Changes in surgical procedures for hypopharynx cancer after definitive radiotherapy are important since the use of pedicled myocutanous flaps and free digestive transplants. Postoperative course is improved and salvage surgery more frequent. From 1970 to 1990, 160 hypopharyngeal carcinomas were operated on after radiotherapy, 103 due to failures or complications after definitive irradiation and 57 metachronous cancers. During this period, the rate of lethal postoperative complications decreased from 25% to 8%. Crude survival rates are 51% at 1 year, 22% at 3 years and 15% at 5 years. Poor prognostic features are local extension, positive margins and extracapsular nodal spread. Postoperative deaths and failures in primary or neck account for 60% of the causes of death. Results of salvage surgery are unsatisfactory: the choice of definitive radiotherapy with surgery in reserve must be restricted to selected cases.

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.

[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.

[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.

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.

Risk factors for simultaneous carcinoma of the head and neck.

The upper aerodigestive tract is a preferential site for multiple primary cancer. The purpose of this study was to determine the characteristics of patients presenting with at least two simultaneous cancers of the upper aerodigestive tract compared with patients with a single location. Men patients (2,738) with squamous cell carcinoma were enrolled in the study. Of these, 120 (4.4%) presented with at least 2 simultaneous cancers (cancers detected within a 6-month period). The group of patients with simultaneous cancers was compared with a group presenting with a single location. Two factors (the mean daily alcohol consumption and employment as a "blue-collar" worker at any time during the working life) seem to be related to the occurrence of simultaneous cancers.

Induction chemotherapy in advanced head and neck cancer. Preliminary results of a randomized study.

From March 1983 to June 1986, 100 patients with locally advanced squamous cell carcinoma of the head and neck were randomized to receive either two courses of chemotherapy prior to local therapy (group A), or local therapy alone (group B). Local treatment consisted of primary radiotherapy in all patients. When a poor response was observed after 55 Gy, surgery was performed. The chemotherapy regimen was a combination of cisplatinum, bleomycin, vindesine, and mitomycin C. The response rate to induction chemotherapy (group A) was 50% for the primary tumor (CR: 10% and PR: 40%). At the end of radiotherapy, the overall tumor response rates in the two groups A and B, were 77% and 79% respectively. Complete disappearance of the primary tumor occurred more often than that of the lymph node metastases. The response rate to induction chemotherapy for lymph node metastases was 27.1% (CR: 9% and PR: 18.1%). An initial major response to chemotherapy predicted subsequent efficacy of irradiation on 90% of the cases, while a failure of chemotherapy had no predictive value in this respect. The survival rates in groups A and B were 66.5% vs. 65.1% at 1 year and 35% vs. 46.2% at 2 years. Local disease-free and disease-free intervals were similar in both groups. A Cox's multi-step regression analysis revealed two significant independant prognostic factors: size of primary tumor and nodal status. After adjustment for these factors, the chemotherapy did not seem to improve the effectiveness of the local treatment in terms of loco-regional control and survival.