Microsatellite instability (MSI) has been associated with favourable survival in early stage colorectal cancer (CRC) compared to microsatellite stable (MSS) CRC. The BRAF V600E mutation has been associated with worse survival in MSS CRC. This mutation occurs in 40% of MSI CRC and it is unclear whether it confers worse survival in this setting. The prognostic value of KRAS mutations in both MSS and MSI CRC remains unclear. We examined the effect of BRAF and KRAS mutations on survival in stage II and III MSI colon cancer patients. BRAF exon 15 and KRAS exon 2–3 mutation status was assessed in 143 stage II (n = 85) and III (n = 58) MSI colon cancers by high resolution melting analysis and sequencing. The relation between mutation status and cancer‐specific (CSS) and overall survival (OS) was analyzed using Kaplan–Meier and Cox regression analysis. BRAF V600E mutations were observed in 51% (n = 73) and KRAS mutations in 16% of cases (n = 23). Patients with double wild‐type cancers (dWT; i.e., BRAF and KRAS wild‐type) had a highly favourable survival with 5‐year CSS of 93% (95% CI 84–100%), while patients with cancers harbouring mutations in either BRAF or KRAS, had 5‐year CSS of 76% (95% CI 67–85%). In the subgroup of stage II patients with dWT cancers no cancer‐specific deaths were observed. On multivariate analysis, mutation in either BRAF or KRAS vs. dWT remained significantly prognostic. Mutations in BRAF as well as KRAS should be analyzed when considering these genes as prognostic markers in MSI colon cancers.

Tangier disease is an extremely rare and severe form of high density lipoprotein deficiency. Even though there is no specific therapy for patients with Tangier disease, it is important to recognize the clinical presentation as patients are at an increased risk of developing atherosclerosis and subsequent CVD. The case discussed in this report, illustrates the importance of recognizing that orange discoloured tonsils are an indication that the patient could be suffering from Tangier's disease.

Background: Little is known about the factors that drive metastasis formation in colorectal cancer (CRC). Here, we set out to identify genes and proteins in patients with colorectal liver metastases that correlate with early disease recurrence. Such factors may predict a propensity for metastasis in earlier stages of CRC. Methods: Gene expression profiling and proteomics were used to identify differentially expressed genes/proteins in resected liver metastases that recurred within 6 months following liver surgery vs those that did not recur for >24 months. Expression of the identified genes/proteins in stage II ( n =243) and III ( n =176) tumours was analysed by immunohistochemistry on tissue microarrays. Correlation of protein levels with stage-specific outcome was assessed by uni- and multivariable analyses. Results: Both gene expression profiling and proteomics identified Maspin to be differentially expressed in colorectal liver metastases with early (<6 months) and prolonged (>24 months) time to recurrence. Immunohistochemical analysis of Maspin expression on tumour sections revealed that it was an independent predictor of time to recurrence (log-rank P =0.004) and CRC-specific survival ( P =0.000) in stage III CRC. High Maspin expression was also correlated with mucinous differentiation. In stage II CRC patients, high Maspin expression did not correlate with survival but was correlated with a right-sided tumour location. Conclusion: High Maspin expression correlates with poor outcome in CRC after spread to the local lymph nodes. Therefore, Maspin may have a stage-specific function possibly related to tumour cell dissemination and/or metastatic outgrowth.

The subwatershed studied drains a non-exploited area of the St-Yrieix-la-Perche gold mining district (French Massif Central) and it is located on an arsenic (As) geochemical anomaly. In this context, it is important to know the geochemical processes involved in the transfer of As from solid environmental compartments to the aquatic system. The stream showed a temporal variation of dissolved As (As(d)) content from 69.4 μg.L(-1) in the low flow period to 7.5 μg.L(-1) in the high flow period. Upstream, ground- and wetland waters had As(d) concentrations up to 215 and 169 μg.L(-1), respectively. The main representative As sources were determined at the subwatershed scale with in-situ monitoring of major and trace element contents in different waters and single extraction experiments. The As sources to stream water could be regrouped into two components: (i) one As-rich group (mainly in the low flow period) with groundwater, gallery exploration outlet waters and wetland waters, and (ii) one As-poor group (mainly in the high flow period) with rainwaters and soil solutions. In the soil profile, As(d) showed a significant decrease from 52.4 μg.L(-1) in the 0-5 cm superficial soil horizon to 14.4 μg.L(-1) in the 135-165 cm deep soil horizon. This decrease may be related to pedogenic processes and suggests an evolution of As-bearing phase stability through the soil profile. Quantification of As(d) fluxes at the subwatershed scale showed that groundwater was the major input (>80%) of As(d) to surface water. Moreover, natural weathering of the As-rich solid phases showed an impact on the As release, mainly from superficial soil horizons with runoff contributing about 5% to As input in surface water.

Arsenic-rich (similar to 140-1520 mg.kg(-1)) suspended particulate matter (SPM) was collected daily with an automatic sampler in the Upper Isle River (France) draining a former gold mining district in order to better understand the fate of arsenic during the suspended transport (particles smaller than 50 pm). Various techniques at a micrometric scale (EPMA, quantitative SEM-EDS with an automated particle counting including classification system and mu XRD) were used to directly characterize As-bearing phases. The most frequent ones were aggregates of fine clay particles. Their mineralogy varied with particle sources involved. These aggregates were formed by chlorite-phlogopite-kaolinite assemblages during the high flow and chlorite-illite-montmorillonite during the low flow. Among all the observed As-carriers in SPM, these clay assemblages were the least As-rich (0.10 up to 1.58 wt.% As) and their median As concentrations suggested that they were less concentrated during the high flow than during the low flow. Iron oxyhydroxides were evidenced by mu XRD in these clay aggregates, either as micro- to nano-sized particles and/or as coating.(Mn, Fe)oxyhydroxides were also present as discrete particles. Manganese oxides (0.14-1.26 wt.% As) transport significantly more arsenic during the low flow than during the high flow (0.16-0.79 wt.% As). The occurrence of Fe oxyhydroxide particles appeared more complex. During the low flow, observations on banks and in wetlands of freshly precipitated Fe hydroxides (ferrihydrite-type) presented the highest As concentrations (up to 6.5 wt.% As) but they were barely detected in SPM at a microscale. During the high flow, As-rich Fe-oxyhydroxides (0.10-2.80 wt.% As) were more frequent, reflecting mechanical erosion and transport when the surface water level increased.Arsenic transfers from SPM to corresponding aqueous fraction mostly depend on As-carrier stability. This study shows the temporal occurrence of each type of As-bearing phases in SPM, their As concentrations at a particle scale and abundance according to hydrological periods. (C) 2011 Elsevier B.V. All rights reserved.

AIM OF THE STUDY:Loss of the nuclear lamina protein lamin A/C (LMNA) has been observed in several human malignancies. The present study aimed to investigate associations between LMNA expression and clinical outcome in colon cancer patients.PATIENTS AND METHODS:Clinicopathological data and formalin-fixed paraffin embedded tissues were collected from 370 stage II and III colon cancer patients. Tissue microarrays were constructed, stained for lamin A/C and evaluated microscopically. Microsatellite instability status was determined for 318 tumours.RESULTS:Low levels of LMNA expression were observed in 17.8% of colon tumours, with disease recurrence occurring in 45.5% of stage II and III colon cancer patients with LMNA-low expressing tumours compared to 29.6% of patients with LMNA-high expressing tumours (p=0.01). For stage II patients, disease recurrence was observed for 35.7% of LMNA-low compared to 20.3% of LMNA-high expressing tumours (p=0.03). Microsatellite stable (MSS) tumours exhibited more frequently low LMNA expression than microsatellite instable (MSI) tumours (21% versus 9.8%; p=0.05). Interestingly, disease recurrence among LMNA-low and LMNA-high expressing MSS tumours varied significantly for stage III patients who had not received adjuvant chemotherapy (100% versus 37.8%; p<0.01) while no such difference was observed for patients who received adjuvant chemotherapy (46.7% versus 46.0%; p=0.96).CONCLUSION:These data indicate that low expression of LMNA is associated with an increased disease recurrence in stage II and III colon cancer patients, and suggest that these patients in particular may benefit from adjuvant chemotherapy.

Background Lymph node (LN) yield in colon cancer resection specimens is an important indicator of treatment quality and has especially in early-stage patients therapeutic implications. However, underlying disease mechanisms, such as microsatellite instability (MSI), may also influence LN yield, as MSI tumors are known to exhibit more prominent lymphocytic antitumor reactions. The aim of the present study was to investigate the association of LN yield, MSI status, and recurrence rate in colon cancer. Methods Clinicopathological data and tumor samples were collected from 332 stage II and III colon cancer patients. DNA was isolated and PCR-based MSI analysis performed. LN yield was defined as “high” when 10 or more LNs were retrieved and “low” in case of fewer than 10 LNs. Results Tumors with high LN yield were significantly associated with the MSI phenotype (high LN yield: 26.3% MSI tumors vs low LN yield: 15.1% MSI tumors; P = .01), mainly in stage III disease. Stage II patients with high LN yield had a lower recurrence rate compared with those with low LN yield. Patients with MSI tumors tended to develop fewer recurrences compared with those with MSS tumors, mainly in stage II disease. Conclusions In the present study, high LN yield was associated with MSI tumors, mainly in stage III patients. Besides adequate surgery and pathology, high LN yield is possibly a feature caused by biologic behavior of MSI tumors.

Background. The prognostic role of pericolic or perirectal isolated tumor deposits (ITDs) in node-negative colorectal cancer (CRC) patients is unclear. Rules to define ITDs as regional lymph node metastases changed in subsequent editions of the TNM staging without substantial evidence. Aim of this study was to investigate the correlation between ITDs and disease recurrence in stage II and III CRC patients. Materials and Methods. The medical files of 870 CRC patients were reviewed. Number, size, shape, and location pattern of all ITDs in node-negative patients were examined in relation to involvement of vascular structures and nerves. The correlation between ITDs and the development of recurrent disease was investigated. Results. Disease recurrence was observed in 50.0% of stage II patients with ITDs (13 of 26), compared with 24.4% of stage II patients without ITDs (66 of 270) (P \ .01). Disease-free survival of ITD-positive stage II patients was comparable with that of stage III patients. Also within stage III, more recurrences were observed in ITD-positive patients compared with ITD-negative patients (65.1 vs. 39.1%, respectively). No correlation was found between size of ITDs and disease recurrence. More recurrences were seen in patients with irregularly shaped ITDs compared with patients with 1 or more smooth ITDs present. Conclusions. Because of the high risk of disease recurrence, all node-negative stage II patients with ITDs, regardless of size and shape, should be classified as stage III, for whom adjuvant chemotherapy should be considered. With more than 600,000 deaths worldwide per year, colorectal cancer (CRC) is the third most common form of cancer and the second leading cause of cancer-related death in the Western world. Currently, the primary method for assessing prognostic differences among patients is the tumor-node-metastasis (TNM) staging system, developed by the American Joint Committee on Cancer and the International Union Against Cancer (UICC). Main therapeutic decisions are based on this classification. Isolated tumor deposits (ITDs) are defined as focal aggregates of adenocarcinoma located in the pericolic or perirectal fat discontinuous with the primary tumor and unassociated with a lymph node. Whether these ITDs should be considered as lymph node involvement when staging the disease has been the subject of discussion for many years, resulting in changes in classification of the disease in subsequent editions of the TNM staging system. Before TNM5, the 5th edition published in 1997, pericolic and perirectal isolated tumor deposits were not classified as positive lymph nodes, regardless of their size and shape, but were classified in the pT-category as pT3. In TNM5, the 3-mm rule was introduced, which states that any mesocolic or mesorectal tumor deposit of 3 mm in size or more should be considered as involved lymph node. In the absence of other evidence of lymph node involvement, this rule resulted in the reclassification of the disease from stage The Author(s) 2010. This article is published with open access at Springerlink.com First Received: 18 February 2010; Published Online: 13 July 2010 E. J. Th. Belt, MD e-mail: ericbelt@hotmail.com Ann Surg Oncol (2010) 17:3203–3211 DOI 10.1245/s10434-010-1152-7

At a watershed scale, sediments and soil weathering exerts a control on solid and dissolved transport of trace elements in surface waters and it can be considered as a source of pollution. The studied subwatershed (1.5 km(2)) was located on an As-geochemical anomaly. The studied soil profile showed a significant decrease of As content from 1500 mg kg(-1) in the 135-165 cm deepest soil layer to 385 mg kg(-1) in the upper 0-5 cm soil layer. Directly in the stream, suspended matter and the <63 mu m fraction of bed sediments had As concentrations greater than 400 mg kg(-1). In all these solid fractions, the main representative As-bearing phases were determined at two different observation scales: bulk analyses using X-ray absorption structure spectroscopy (XAS) and microanalyses using scanning electron microscope (SEM) and associated electron probe microanalyses (EPMA), as well as micro-Raman spectroscopy and synchrotron-based micro-scanning X-ray diffraction (mu SXRD) characterization. Three main As-bearing phases were identified: (i) arsenates (mostly pharmacosiderite), the most concentrated phases As in both the coherent weathered bedrock and the 135-165 cm soil layer but not observed in the river solid fraction, (ii) Fe-oxyhydroxides with in situ As content up to 15.4 wt.% in the deepest soil layer, and (iii) alumino-silicates, the least concentrated As carriers. The mineralogical evolution of As-bearing phases in the soil profile, coupled with the decrease of bulk As content, may be related to pedogenesis processes, suggesting an evolution of arsenates into As-rich Fe-oxyhydroxides. Therefore, weathering and mineralogical evolution of these As-rich phases may release As to surface waters. (C) 2010 Elsevier Ltd. All rights reserved.

The Upper Isle River (SW France) drains the second most productive gold-mining district of France. A high resolution survey during one hydrological year of As, Cl-, Cr, Fe, Mn, Mo, SO42-, Th and U dissolved concentrations in surface water aimed to better understand pathways of trace element export to the river system downstream from the mining district. Dissolved concentrations of As (up to 35 000 ng/L) and Mo (up to 292 ng/L) were about 3-fold higher than the regional dissolved background and showed a negative logarithmic relation with discharge. Dissolved concentrations of Cr (up to 483 ng/L), Th (up to 48 ng/L) and U (up to 184 ng/L) increased with discharge. Geochemical relationships between molar ratios in surface water, geochemical background as well as rain- and groundwater data were combined. The contrasting behavior of distinct element groups was explained by a scenario involving three seasonal components: (i) The high flow component is poorly concentrated in As and Mo but highly concentrated in Cr, Th, U. This has been attributed to diffuse sources such as water-soil interactions, atmospheric inputs, bedrock and bed sediment weathering. Although this component probably also includes a contribution by weathering of sulfide veins, this signal is masked by dilution. (ii) One low flow component presents high SO42-, Fe, As and Mo and moderate Cr, Th and U concentrations. This component has been attributed to point sources such as mine gallery effluents, mining waste weathering and groundwater inputs from natural and/or mining-induced sulfide oxidation in the ore deposit. (iii) A second low flow component showing high As plus Mo concentrations associated with very low SO42-, Fe, Cr, Th and U concentrations, probably reflects trace element scavenging by ferric oxyhydroxide formation in the adjacent aquifer. This is supported by the decrease of Fe, Cr, Th and U in surface waters. Flux estimates suggest contrasting element-specific impacts on annual dissolved fluxes. Runoff may account for the major part of annual dissolved As, Mo, Th and U fluxes in the Upper Isle River. Inputs related to sulfide oxidation respectively contributed similar to 30% and similar to 24% to annual As and Mo fluxes. The formation of ferric oxyhydroxides strongly retained Cr, Th and U during the low flow, limiting their dissolved concentrations in surface waters. If this process may eventually decrease As mobility, its impact on dissolved As concentrations in surface water may be limited or/and counterbalanced by As release during sulfide oxidation. (c) 2008 Elsevier B.V. All rights reserved.

The study area (Szklary Massif, SW Poland) comprises three sites of different soil provenance: (1) natural serpentine Cambisol, (2) anthroposol situated on waste dump and (3) cultivated Inceptisol developed on glacial tills next to the dump. Potentially toxic elements (PTE) have either lithogenic or anthropogenic origins in these sites. The chemical partitioning of Co, Cr, Cu, Ni, Pb and Zn among solid forms was determined by sequential extractions coupled with direct mineral identifications (SEM, electron microprobe analysis – EMPA, and XRD). Examination of solid residues after several extraction steps was conducted in order to discuss the indirect speciation obtained by the extraction method. Total concentrations of PTE having anthropogenic origin greatly exceed those of lithogenic origin. Mobility of studied PTE is variable in the different environments except for Cr which is always mostly found in residual fractions of extractions. Cu and Pb are more mobile than Cr and Co in all soils. Zn is more stable (Cu > Pb > Ni > Co > Zn >> Cr) in the serpentine soil and cultivated epipedon (Pb > Cu > Zn > Ni > Co >> Cr) than in the anthroposol (Zn > Cu ⩾ Pb > Ni > Co >> Cr). PTE of lithogenic origin are generally less mobile than those from anthropogenic origin except Ni which is more mobile in the serpentine soil. Nonetheless, mineral forms of metals better determine their mobility than metal origin. Identification by direct methods of the PTE mineral form was not possible for metals present at low concentrations (Cu, Pb). However, direct mineralogical examinations of the solid residues of several extractions steps improved the assessment of the PTE solid speciation and mobility, particularly for Cr, Ni and Zn.

Part of the soils occurring in the serpentinite Szklary Massif (SW Poland) have developed in Quaternary under temperate climate on the parent rock not affected by chemical weathering. In studied parent ultrabasite, Ni occurs in Cr-magnetite (up to 0.96 wt.% of NiO), forsterite (up to 0.55 wt.% of NiO), iddingsite (up to 0.99 wt.% of NiO), and serpentine (up to 0.55 wt.% of NiO), while Cr is bounded with Cr-magnetites (up to 21.77 wt.% of Cr2O3) and clinochlores (up to 1.68 wt.% of Cr2O3). Cr-magnetites are highly resistant to weathering while other primary minerals, more susceptible to weathering release parts of Ni and Cr which are trapped in authigenic phases. The latter, however, contain less Ni and Cr than corresponding primary minerals: clayous matrix 0.37 wt.% of NiO and 0.08 wt.% of Cr2O3, smectites 0.30 wt.% of NiO and 0.07 wt.% of Cr2O3 and mixture of oxy-hydroxides and clay minerals 0.36 wt.% of NiO and 0.14 wt.% of Cr2O3. At the mineral scale, smectite plays an important role in the trapping of Ni. At the profile scale, Ni and Cr are moderately diluted upwards the soil profile and Cr is generally less mobile than Ni. The soil formed in Szklary is chemically different than the analogous serpentine soils occurring more to the south in Europe (French Massif Central, Vosges Mountains and Ligurian Apennines, NW Italy). The difference is due to participation of fluvioglacial material produced by Quaternary continental glaciacion in Poland. However, similar vertical relative variations of Ni and Cr were found in all compared soils in spite of differences in parent rock composition, allogenic contaminations and degree of soil development. Comparison with other well-drained pedons located in similar uphill positions shows a climatic control of the Cr and Ni vertical distribution in serpentine soils. Humid mountainous variant of temperate climate induces leaching of Mg and subsequent lack in smectite neoformation which lead to the release of Ni. Ni is less mobile in the colder and dryer climate of Poland. Moreover, some primary minerals which are generally considered as not stable under soil conditions (olivine, serpentine and chlorite) are still present even in the A horizon of the studied Polish pedon. Their resistance is due to slower rates of weathering related to the climate but also due to former hydrothermal processes affecting the parent rock fabric. (C) 2007 Elsevier B.V. All rights reserved.

Arsenic-bearing stream sediments enter the Upper Isle River, an Au mining-influenced basin (France), by the discharge of mining sites, tailings runoff and weathering of mineralized veins in granites and gneiss. Some fresh ochreous As-rich deposits on the river banks and in floodplains are identified as additional As-rich point sources (As between 0.07 and 6.5wt.%). The <63μm fraction of stream sediments contains elevated As bulk concentrations, ranging from 160 to 890mg/kg, compared to the geochemical background (70mg/kg on average). It is also enriched in Cd, Hg and W. Spatial variations of these trace elements show 3 significant increases corresponding to the 3 drained mining districts. They decrease down river but are still enriched 30km downstream of the mining districts due to downstream transportation. Three types of trace element-bearing phases have been identified as: (i) detrital primary sulfides, with high in situ As percentages (up to 43.7wt.%). They also carry significant amounts of W according to the differences in chemical compositions of the total and light <63μm fractions. These sulfide particles do not show any sign of alteration in the oxygenated stream sediments; (ii) Secondary Fe–Mn oxyhydroxides,some with very high in situ As2O5 concentrations (up to 59.8wt.%) and with about 40% of the total Cd composition. They occur as fresh precipitates in the river banks and floodplains and as discrete particles in stream sediments and (iii) Al–Si fine-grained phases. Their major element composition is highly variable with in situ As2O5 concentrations ranging between 430 and 5020mg/kg. This type of solid phase is also the major carrier of Hg.

Either from natural or anthropic origin, be it normal or accidental (Tchernobyl), metallic elements are found everywhere in our environment. After a presentation of their repartition and mobility in water, sediments or soils, the mechanisms allowing their dispersion or their concentration are shown. Finally, transfers between environmental compartments are presented, before evoking the case of polluted sites: diagnostic, remediation and long-time management.

Bulk Cr, Cu, Ni, Pb and Zn contents were analyzed in a Cr–Ni rich basalt, derived andic soil and in grass subaerial and aerial components to assess natural trace metal mobility in soil. Phytoavailability and relative mobility of elements were quantified by three different approaches: selective extractions, calculation at mineral scale after XRD, SEM-EDS and EMP analyses and measurement of pools at profile scale. Pool variations from rock to soil horizons give a view of the long-term mobility, while selective extractions and comparisons of pools measured in plants and top soil provide estimations of the current mobility and bioavailability. Major amounts of trace metals were held in the solid constituents of the soil. Examination of the solid residues following extractions clarified the potential mobility of these metal containing solids. Water soluble and exchangeable fractions never exceed 3% of the total trace metal amounts, which is of similar magnitude to pools found in grass roots and shoots. Zinc is the most easily extracted element followed by Cu, Ni and Cr. Over the short term, Zn also occurs in greater amounts in grass. Its involvement in organic matter turnover explains its greater accumulation in the soil profile over the long term. Chromium and Ni which are predominantly held in stable minerals (spinels) are less available for plants in the short term. They are both relatively depleted in soil, compared to initial pools in rock, over the long term. From a methodological point of view, the results demonstrate the necessity of comparing selective extraction data with other quantitative methods for assessing both short-term and long-term trace metal mobility and bioavailability.

The objective of this study is to identify parameters influencing trace elements (TE) vertical distributions in an Andosol–Andic Cambisol climosequence. In order to understand processes involved in the current distribution of trace elements from basaltic rocks to associated soils, six pedons developed on Tertiary massive basaltic formations, located at similar position in the hill-slopes, submitted to the same wet mountainous climate but under various microclimatic conditions (altitude and annual rainfall), were considered. The six studied soils are andic and rich in organo–metallic complexes. Two different and quantitative methods were used to compare the geochemical distributions of major and trace elements, both being calculated with Ti as invariant element: isovolumetric mass balance and enrichment factors. Anthropogenic, pedogenetic, microclimatic, inherited factors were discriminated. Anthropogenic influences are pointed out for K in two pedons and for Pb in all studied sites. Distributions of other TE are affected by discontinuities between underlying rocks and soil horizons. Zinc and Cu distributions are controlled by organic matter whereas Cr and Ni distributions are influenced by pedogenetic processes. Results emphasize the relative trace element immobilization in andic soils under temperate climate.