Differences in survival and recurrence of colorectal cancer by stage across population-based European registries.

Recurrence after colorectal cancer resection is rarely documented in the general population while a key clinical determinant for patient survival. We identified 8785 patients with colorectal cancer diagnosed between 2010 and 2013 and clinically followed up to 2020 in 15 cancer registries from seven European countries (Bulgaria, Switzerland, Germany, Estonia, France, Italy, and Spain). We estimated world age-standardized net survival using a flexible cumulative excess hazard model. Recurrence rates were calculated for patients with initially resected stage I, II, or III cancer in six countries, using the actuarial survival method. The proportion of nonmetastatic resected colorectal cancers varied from 58.6% to 78.5% according to countries. The overall 5-year net survival by country ranged between 60.8% and 74.5%. The absolute difference between the 5-year survival extremes was 12.8 points for stage II (Bulgaria vs Switzerland), 19.7 points for stage III (Bulgaria vs. Switzerland) and 14.8 points for Stage IV and unresected cases (Bulgaria vs. Switzerland or France). Five-year cumulative rate of recurrence among resected patients with stage I-III was 17.7%. As compared to the mean of the whole cohort, the risk of developing a recurrence did not differ between countries except a lower risk in Italy for both stage I/II and stage III cancers and a higher risk in Spain for stage III. Survival after colorectal cancer differed across the concerned European countries while there were slight differences in recurrence rates. Population-based collection of cancer recurrence information is crucial to enhance efforts for evidence-based management of colorectal cancer follow up.

Access to primary care and mortality in excess for patients with cancer in France: Results from 21 French Cancer Registries.

BACKGROUND: The impact of geographical accessibility on cancer survival has been investigated in few studies, with most research focusing on access to reference care centers, using overall mortality and limited to specific cancer sites. This study aims to examine the association of access to primary care with mortality in excess of patients with the 10 most frequent cancers in France, while controlling for socioeconomic deprivation. METHODS: This study included a total of 151,984 cases diagnosed with the 10 most common cancer sites in 21 French cancer registries between 2013 and 2015. Access to primary care was estimated using two indexes: the Accessibilité Potentielle Localisée index (access to general practitioners) and the Scale index (access to a range of primary care clinicians). Mortality in excess was modelized using an additive framework based on expected mortality based on lifetables and observed mortality. FINDINGS: Patients living in areas with less access to primary care had a greater mortality in excess for some very common cancer sites like breast (women), lung (men), liver (men and women), and colorectal cancer (men), representing 46% of patients diagnosed in our sample. The maximum effect was found for breast cancer; the excess hazard ratio was estimated to be 1.69 (95% CI, 1.20-2.38) 1 year after diagnosis and 2.26 (95% CI, 1.07-4.80) 5 years after diagnosis. INTERPRETATION: This study revealed that this differential access to primary care was associated with mortality in excess for patients with cancer and should become a priority for health policymakers to reduce these inequalities in health care accessibility.

Prognostic impact of DDX41 germline mutations in intensively treated acute myeloid leukemia patients: an ALFA-FILO study.

DDX41 germline mutations (DDX41MutGL) are the most common genetic predisposition to myelodysplastic syndrome and acute myeloid leukemia (AML). Recent reports suggest that DDX41MutGL myeloid malignancies could be considered as a distinct entity, even if their specific presentation and outcome remain to be defined. We describe here the clinical and biological features of 191 patients with DDX41MutGL AML. Baseline characteristics and outcome of 86 of these patients, treated with intensive chemotherapy in 5 prospective Acute Leukemia French Association/French Innovative Leukemia Organization trials, were compared with those of 1604 patients with DDX41 wild-type (DDX41WT) AML, representing a prevalence of 5%. Patients with DDX41MutGL AML were mostly male (75%), in their seventh decade, and with low leukocyte count (median, 2 × 109/L), low bone marrow blast infiltration (median, 33%), normal cytogenetics (75%), and few additional somatic mutations (median, 2). A second somatic DDX41 mutation (DDX41MutSom) was found in 82% of patients, and clonal architecture inference suggested that it could be the main driver for AML progression. DDX41MutGL patients displayed higher complete remission rates (94% vs 69%; P < .0001) and longer restricted mean overall survival censored at hematopoietic stem cell transplantation (HSCT) than 2017 European LeukemiaNet intermediate/adverse (Int/Adv) DDX41WT patients (5-year difference in restricted mean survival times, 13.6 months; P < .001). Relapse rates censored at HSCT were lower at 1 year in DDX41MutGL patients (15% vs 44%) but later increased to be similar to Int/Adv DDX41WT patients at 3 years (82% vs 75%). HSCT in first complete remission was associated with prolonged relapse-free survival (hazard ratio, 0.43; 95% confidence interval, 0.21-0.88; P = .02) but not with longer overall survival (hazard ratio, 0.77; 95% confidence interval, 0.35-1.68; P = .5).

Impact of socio-economic environment on incidence of primary liver cancer in France between 2006 and 2016.

BACKGROUND AND AIMS: To measure the impact of socio-economic environment on the incidence of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). METHOD: The study used data from the French Network of Cancer Registries (FRANCIM) between 2006 and 2016. Classification of patients into HCC and iCCA was performed according to the topographical and morphological codes of the 3rd edition of the International Classification of Diseases for Oncology. Patient addresses were geolocalized and assigned to an IRIS, the smallest French geographic unit. Socio-economic environment was assessed by the European Deprivation Index (EDI). Sex- and age-standardized incidence rates with 95% confidence intervals (CI) were estimated per 100 000 inhabitants, by national quintiles, for each IRIS, sex and age group. Quintile 1 (Q1) characterized the most affluent areas. A Poisson regression was performed to model the impact of deprivation. RESULTS: We included 22 249 cases (79.64% HCC, 16.97% iCCA). Incidence rates were 11.46 and 2.39 per 100 000 person-years for HCC and iCCA, respectively. There was an over-incidence of HCC in quintiles 2, 3, 4 and 5 compared to quintile 1: Q1 10.28 [9.9-10.66] per 100 000 person-years, Q2 11.43 [10.48-12.47] (p < .0001), Q3 11.81 [10.82-12.89] (p < .0001), Q4 12.26 [11.25-13.37] (p < .001) and Q5 11.53 [10.57-12.57] (p < .0001). By contrast, there was no difference for iCCa. Deprivation was significantly associated with HCC in men (p = .0018) and women (p = .0009), but not with iCCA (p = .7407). CONCLUSION: The incidence of HCC is related to socio-economic environment, unlike iCCA. HCC and iCCA should be studied separately in epidemiological studies.

A modern scleractinian coral with a two-component calcite-aragonite skeleton.

One of the most conserved traits in the evolution of biomineralizing organisms is the taxon-specific selection of skeletal minerals. All modern scleractinian corals are thought to produce skeletons exclusively of the calcium-carbonate polymorph aragonite. Despite strong fluctuations in ocean chemistry (notably the Mg/Ca ratio), this feature is believed to be conserved throughout the coral fossil record, spanning more than 240 million years. Only one example, the Cretaceous scleractinian coral Coelosmilia (ca. 70 to 65 Ma), is thought to have produced a calcitic skeleton. Here, we report that the modern asymbiotic scleractinian coral Paraconotrochus antarcticus living in the Southern Ocean forms a two-component carbonate skeleton, with an inner structure made of high-Mg calcite and an outer structure composed of aragonite. P. antarcticus and Cretaceous Coelosmilia skeletons share a unique microstructure indicating a close phylogenetic relationship, consistent with the early divergence of P. antarcticus within the Vacatina (i.e., Robusta) clade, estimated to have occurred in the Mesozoic (ca. 116 Mya). Scleractinian corals thus join the group of marine organisms capable of forming bimineralic structures, which requires a highly controlled biomineralization mechanism; this capability dates back at least 100 My. Due to its relatively prolonged isolation, the Southern Ocean stands out as a repository for extant marine organisms with ancient traits.

Relationship between comorbidities, mutational profile, and outcome after intensive chemotherapy in patients older than 60 years with acute myeloid leukemia: Assessment of different risk scores.

The aim of this study was to evaluate how comorbidities and molecular landscape relate to outcome in patients with acute myeloid leukemia (AML) aged 60 years or older who received intensive induction therapy. In 91 patients, 323 mutations were identified in 77 genes by next-generation sequencing, with a median of four mutations per patient, with NPM1, FLT3, TET2, and DNMT3A being the most frequently mutated genes. A multistate model identified FLT3, IDH2, RUNX1, and TET2 mutations as associated with a higher likelihood of achieving complete remission while STAG2 mutations were associated with primary refractory disease, and DNMT3A, FLT3, IDH2, and TP53 mutations with mortality after relapse. Ferrara unfitness criteria and performance status were the best predictors of short-term outcome (area under the curve = 82 for 2-month survival for both parameters), whereas genomic classifications better predicted long-term outcome, with the Patel risk stratification performing the best over the 5-year follow-up period (C-index = 0.63 for event-free and overall survival). We show that most genomic prognostic classifications, mainly used in younger patients, are useful for classifying older patients, but to a lesser extent, because of different mutational profiles. Specific prognostic classifications, incorporating performance status, comorbidities, and cytogenetic/molecular data, should be specifically designed for patients over 60 years.

First estimates of diffuse gastric cancer risks for carriers of CTNNA1 germline pathogenic variants.

BACKGROUND: Pathogenic variants (PV) of CTNNA1 are found in families fulfilling criteria for hereditary diffuse gastric cancer (HDGC) but no risk estimates were available until now. The aim of this study is to evaluate diffuse gastric cancer (DGC) risks for carriers of germline CTNNA1 PV. METHODS: Data from published CTNNA1 families were updated and new families were identified through international collaborations. The cumulative risk of DGC by age for PV carriers was estimated with the genotype restricted likelihood (GRL) method, taking into account non-genotyped individuals and conditioning on all observed phenotypes and genotypes of the index case to obtain unbiased estimates. A non-parametric (NP) and the Weibull functions were used to model the shape of penetrance function with the GRL. Kaplan-Meier incidence curve and standardised incidence ratios were also computed. A 'leave-one-out' strategy was used to evaluate estimate uncertainty. RESULTS: Thirteen families with 46 carriers of PV were included. The cumulative risks of DGC at 80 years for carriers of CTNNA1 PV are 49% and 57%, respectively with the Weibull GRL and NP GRL methods. Risk ratios to population incidence reach particularly high values at early ages and decrease with age. At 40 years, they are equal to 65 and 833, respectively with the Weibull GRL and NP GRL. CONCLUSION: This is the largest series of CTNNA1 families that provides the first risk estimates of GC. These data will help to improve management and surveillance for these patients and support inclusion of CTNNA1 in germline testing panels.

Biliary tract cancers have distinct epidemiological patterns and clinical characteristics according to tumour site.

BACKGROUND: Little is known about the epidemiology of biliary tract cancers over the last decade. We investigated trends in incidence, treatment and prognosis of biliary tract cancers according to anatomic site. METHODS: 714 biliary tract cancers recorded between 2012 and 2019 in the French population-based cancer registry of Burgundy were included. Trends in world age-standardized incidence were depicted using Poisson regression. RESULTS: Intrahepatic cholangiocarcinoma accounted for 40% of biliary tract cancer. Half of the patients were older than 75 years at diagnosis. Incidence of biliary tract cancer did not vary over time, except a slight increase in intrahepatic cholangiocarcinoma in men and a decrease in the ampulla in both sexes. Among non-metastatic patients, the proportion who underwent R0 resection ranged from 15% for intrahepatic cholangiocarcinoma to 58% for ampulla cancer (p < 0.001). Age, performance status and hospital type were associated with resection. Among unresected patients, 45% received chemotherapy. Older age, jaundice, increasing performance status and comorbidities index negatively affected chemotherapy administration. Net survival was higher for ampulla than for other sites, regardless of patient and treatment characteristics. CONCLUSION: Biliary tract cancers present different patterns in incidence. The ampulla site should be considered separately in clinical trials due to its better outcomes.

Health status of prevalent cancer cases as measured by mortality dynamics (cancer vs. noncancer): Application to five major cancers sites.

BACKGROUND: Cancer prevalence is heterogeneous because it includes individuals who are undergoing initial treatment and those who are in remission, experiencing relapse, or cured. The proposed statistical approach describes the health status of this group by estimating the probabilities of death among prevalent cases. The application concerns colorectal, lung, breast, and prostate cancers and melanoma in France in 2017. METHODS: Excess mortality was used to estimate the probabilities of death from cancer and other causes. RESULTS: For the studied cancers, most deaths from cancer occurred during the first 5 years after diagnosis. The probability of death from cancer decreased with increasing time since diagnosis except for breast cancer, for which it remained relatively stable. The time beyond which the probability of death from cancer became lower than that from other causes depended on age and cancer site: for colorectal cancer, it was 6 years after diagnosis for women (7 years for men) aged 75-84 and 20 years for women (18 years for men) aged 45-54 years, whereas cancer was the major cause of death for women younger than 75 years whatever the time since diagnosis for breast and for all patients younger than 75 years for lung cancer. In contrast, deaths from other causes were more frequent in all the patients older than 75 years. Apart from breast cancer in women younger than 55 years and lung cancer in women older than 55 years and men older than 65 years, the probability of death from cancer among prevalent cases fell below 1%, with varying times since diagnosis. CONCLUSIONS: The authors' approach can be used to better describe the burden of cancer by estimating outcomes in prevalent cases.

Overall and net survival of patients with sarcoma between 2005 and 2010: Results from the French Network of Cancer Registries (FRANCIM).

BACKGROUND: Sarcomas are rare, heterogeneous, ubiquitously localized malignancies with many histologic subtypes and genomic patterns. The survival of patients with sarcoma has rarely been described based on this heterogeneity; therefore, the authors' objective was to estimate survival outcomes in patients who had sarcomas using the 2020 version of the World Health Organization classification of soft tissue and bone tumors. METHODS: Patients older than 15 years who had incident sarcoma diagnosed between 2005 and 2010 were extracted from 14 French population-based cancer registries covering 18% of the French metropolitan population. Vital status for each patient was actively followed up to June 30, 2013. Net survival (NS) was estimated using the unbiased Pohar-Perme method. RESULTS: Overall, 4202 patients were included. NS declined with increasing age at diagnosis. According to topographic groups, large 5-year NS disparities were observed, ranging from 47% among women with gynecologic sarcomas to 89% among patients with skin sarcomas. Patients with soft tissue, bone, and gastrointestinal sarcomas had 5-year NS rates of 53%, 61%, and 70%, respectively. Similar heterogeneity was observed according to histologic subtypes, with 5-year NS ranging from 19% for patients with angiosarcomas to 96% for patients with dermatofibrosarcomas. Patients with sarcoma who displayed missense mutations had a better 5-year NS (74%); those with MDM2-amplified sarcomas had the worst NS (45%). CONCLUSIONS: NS rates in patients with sarcoma are presented here for the first time based on the 2020 World Health Organization classification applied to population-based registry data. Large prognostic heterogeneity was observed based on age, topographic and histologic groups, and genomic alteration profiles, constituting a benchmark for future studies and clinical trials.

Surface Analysis by Secondary Ion Mass Spectrometry (SIMS): Principles and Applications from Swiss laboratories.

Secondary Ion Mass Spectrometry (SIMS) extracts chemical, elemental, or isotopic information about a localized area of a solid target by performing mass spectrometry on secondary ions sputtered from its surface by the impact of a beam of charged particles. This primary beam sputters ionized atoms and small molecules (as well as many neutral particles) from the upper few nanometers of the sample surface. The physical basis of SIMS has been applied to a large range of applications utilizing instruments optimized with different types of mass analyzer, either dynamic SIMS with a double focusing mass spectrometer or static SIMS with a Time of Flight (TOF) analyzer. Here, we present a short review of the principles and major applications of three different SIMS instruments located in Switzerland.

Colorectal cancer incidence, mortality, and stage distribution in European countries in the colorectal cancer screening era: an international population-based study.

BACKGROUND: Colorectal cancer screening programmes and uptake vary substantially across Europe. We aimed to compare changes over time in colorectal cancer incidence, mortality, and stage distribution in relation to colorectal cancer screening implementation in European countries. METHODS: Data from nearly 3·1 million patients with colorectal cancer diagnosed from 2000 onwards (up to 2016 for most countries) were obtained from 21 European countries, and were used to analyse changes over time in age-standardised colorectal cancer incidence and stage distribution. The WHO mortality database was used to analyse changes over time in age-standardised colorectal cancer mortality over the same period for the 16 countries with nationwide data. Incidence rates were calculated for all sites of the colon and rectum combined, as well as the subsites proximal colon, distal colon, and rectum. Average annual percentage changes (AAPCs) in incidence and mortality were estimated and relevant patterns were descriptively analysed. FINDINGS: In countries with long-standing programmes of screening colonoscopy and faecal tests (ie, Austria, the Czech Republic, and Germany), colorectal cancer incidence decreased substantially over time, with AAPCs ranging from -2·5% (95% CI -2·8 to -2·2) to -1·6% (-2·0 to -1·2) in men and from -2·4% (-2·7 to -2·1) to -1·3% (-1·7 to -0·9) in women. In countries where screening programmes were implemented during the study period, age-standardised colorectal cancer incidence either remained stable or increased up to the year screening was implemented. AAPCs for these countries ranged from -0·2% (95% CI -1·4 to 1·0) to 1·5% (1·1 to 1·8) in men and from -0·5% (-1·7 to 0·6) to 1·2% (0·8 to 1·5) in women. Where high screening coverage and uptake were rapidly achieved (ie, Denmark, the Netherlands, and Slovenia), age-standardised incidence rates initially increased but then subsequently decreased. Conversely, colorectal cancer incidence increased in most countries where no large-scale screening programmes were available (eg, Bulgaria, Estonia, Norway, and Ukraine), with AAPCs ranging from 0·3% (95% CI 0·1 to 0·5) to 1·9% (1·2 to 2·6) in men and from 0·6% (0·4 to 0·8) to 1·1% (0·8 to 1·4) in women. The largest decreases in colorectal cancer mortality were seen in countries with long-standing screening programmes. INTERPRETATION: We observed divergent trends in colorectal cancer incidence, mortality, and stage distribution across European countries, which appear to be largely explained by different levels of colorectal cancer screening implementation. FUNDING: German Cancer Aid (Deutsche Krebshilfe) and the German Federal Ministry of Education and Research.

Molecular classification and prognosis in younger adults with acute myeloid leukemia and intermediate-risk cytogenetics treated or not by gemtuzumab ozogamycin: Final results of the GOELAMS/FILO acute myeloid leukemia 2006-intermediate-risk trial.

In this randomized phase 3 study, the FILO group tested whether the addition of 6 mg/m2 of gemtuzumab ozogamycin (GO) to standard chemotherapy could improve outcome of younger patients with de novo acute myeloid leukemia (AML) and intermediate-risk cytogenetics. GO arm was prematurely closed after 254 inclusions because of toxicity. A similar complete remission rate was observed in both arms. Neither event-free survival nor overall survival were improved by GO in younger AML patients (<60 years) ineligible for allogeneic stem-cell transplantation. (P = .086; P = .149, respectively). Using unsupervised hierarchical clustering based on mutational analysis of seven genes (NPM1, FLT3-ITD, CEBPA, DNMT3A, IDH1, IDH2, and ASXL1), six clusters of patients with significant different outcome were identified. Five clusters were based on FLT3-ITD, NPM1, and CEBPA mutations as well as epigenetic modifiers (DNMT3A, IDH1/2, ASXL1), whereas the last cluster, representing 25% of patients, had no mutation and intermediate risk. One cluster isolated FLT3-ITD mutations with higher allelic ratio and a very poor outcome. The addition of GO had no impact in these molecular clusters. Although not conclusive for GO impact in AML patients <60 years, this study provides a molecular classification that distinguishes six AML clusters influencing prognosis in younger AML patients with intermediate-risk cytogenetic.

High-spatial-resolution measurements of iron isotopes in pyrites by secondary ion mass spectrometry using the new Hyperion-II radio-frequency plasma source.

RATIONALE: Iron isotopic signatures in pyrites are considered as a good proxy for reconstructing paleoenvironmental and local redox conditions. However, the investigation of micro-pyrites less than 20 µm in size has been limited by the available analytical techniques. The development of a new brighter radio-frequency plasma ion source (Hyperion-II source) enhances the spatial resolution by increasing the beam density 10 times compared with the Duoplasmatron source. METHODS: Here we present high-spatial-resolution measurements of iron isotopes in pyrites using a 3 nA-3 µm primary 16 O- beam on two Cameca IMS 1280-HR2 ion microprobe instruments equipped with Hyperion sources at CRPG-IPNT (France) and at SwissSIMS (Switzerland). We tested analytical effects, such as topography and crystal orientation, that could induce analytical biases perceptible through variations of the instrumental mass fractionation (IMF). RESULTS: The δ56 Fe reproducibility for the Balmat pyrite standard is ±0.25‰ (2 standard deviations) and the typical individual internal error is ±0.10‰ (2 standard errors). The sensitivity on 56 Fe+ was 1.2 × 107 cps/nA/ppm or better. Tests on Balmat pyrites revealed that neither the crystal orientation nor channeling effects seem to significantly influence the IMF. Different pyrite standards (Balmat and SpainCR) were used to test the accuracy of the measurements. Indium mounts must be carefully prepared with a sample topography less than 2 µm, which was checked using an interferometric microscope. Such a topography is negligible for introducing change in the IMF. This new source increases the spatial resolution while maintaining the high precision of analyses and the overall stability of the measurements compared with the previous Duoplasmatron source. CONCLUSIONS: A reliable method was developed for performing accurate and high-resolution measurements of micrometric pyrites. The investigation of sedimentary micro-pyrites will improve our understanding of the processes and environmental conditions during pyrite precipitation, including the contribution of primary (microbial activities or abiotic reactions) and secondary (diagenesis and/or hydrothermal fluid circulation) signatures.

Incidence and time trends of sarcoma (2000-2013): results from the French network of cancer registries (FRANCIM).

BACKGROUND: The exhaustive collection of new sarcoma cases and their second histologic review offer a unique opportunity to study their incidence and time trends in France according to the major subtypes. METHODS: Data were collected from population-based cancer registries covering 22% of the French population. Crude and world age-standardized incidence rates (ASR) were estimated according to anatomic, histological and genetic groups, age and sex over the 2010-2013 period. RESULTS: Time trends in incidence were calculated by the annual percent change over the 2000-2013 period. During the most recent period (2010-2013), 3942 patients with sarcoma were included. The ASR of soft-tissue and bone sarcomas, and gastro-intestinal stromal tumors (GIST) were 2.1, 1.0 and 0.6, respectively. For the four most frequent histological subtypes (unclassified, leiomyosarcoma, GIST and liposarcoma), the ASR ranged from 0.4 to 0.7. ASRs were 1.9 for complex genomic and 1.3 for recurrent translocation sarcomas. The time-trend analysis showed a significant increase of sarcoma incidence rate between 2000 and 2005, which stabilized thereafter. Incidence rates increased for four histological subtypes (GIST, chondrosarcoma, myxofibrosarcoma, solitary fibrous tumors) and decreased for three (leiomyosarcomas, Kaposi sarcoma and fibrosarcoma). CONCLUSION: To our knowledge, this study is the first to investigate sarcoma incidence based on a systematic pathological review of these cancers and on the updated sarcoma classifications. Due to the paucity of literature on sarcomas, future studies using data from population-based cancer registries should consider a standardized inclusion criterion presented in our study to better describe and compare data between countries.

Outcomes following polypectomy for malignant colorectal polyps are similar to those following surgery in the general population.

OBJECTIVE: Population-based studies on colorectal malignant polyps (MPs) are scarce. The aim of this study was to describe time trends in the incidence of colorectal MPs before and after the introduction of a colorectal mass-screening programmein 2003 and to assess outcomes (survival and recurrence) after endoscopic or surgical resection in patients with MPs. DESIGN: We included 411 patients with MPs diagnosed between 1982 and 2011 in a well-defined population. Age-standardised incidence rates were calculated. Univariate and multivariate 5-year recurrence and net survival analyses were performed according to gross morphology. RESULTS: Age-standardised incidence of MPs in patients aged 50-74 years doubled from 5.4 in 1982-2002 to 10.9 per 100 000 in 2003-2011. Pedunculated MPs were more frequently resected endoscopically (38.2%) than were sessile MPs (19.1%; p<0.001). For patients with pedunculated MPs and a pathological margin ≥1 mm, the 5 -year cumulative recurrence rate did not differ significantly between surgical and endoscopic resection (8.2% and 2.4%, respectively). For patients with sessile MPs, it was 3.0% after first-line or second-line surgical resection, 8.6% after endoscopic resection and 17.9% after transanal resection (p=0.016). The recurrence rate decreased dramatically for patients with sessile MPs from 11.3% (1982-2002) to 1.2% (2003-2009) (p=0.010) and remained stable for pedunculated MPs at 4.6% and 6.7%, respectively. Five-year net survival was 81.0% when pathological margins were <1 mm and 95.6% when ≥1 mm (p=0.024). CONCLUSION: Outcomes following polypectomy in patients with a pathological margin ≥1 mm are similar to those following surgery in the general population. Endoscopic resection needs to be completed by surgery if pathological margins are less than 1 mm.

WT1 gene is overexpressed in myeloproliferative neoplasms, especially in myelofibrosis.

Classical Philadelphia-negative myeloproliferative neoplasms include Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF). They are characterized by the presence of driver mutations of JAK2, CALR or MPL genes. Overexpression of WT1 is used as a marker of minimal residual disease in acute myeloid leukemia, especially after allogeneic stem cell transplantation (SCT). We investigated WT1 expression at diagnosis in 152 MPN patients and showed that the WT1 transcript was overexpressed in PMFs and PVs compared to controls. In particular, WT1 transcript levels were higher in PMF than in ET and PV. WT1 transcript levels were significantly increased during myelofibrotic transformation of ET or PV. Using multivariate linear regression, high WT1 transcript levels in PMF were associated with age over 65, splenomegaly and thrombocytopenia. The ROC curve analysis showed that a level of WT1 transcript >10 WT1 copies/104ABL1 enabled the diagnosis of PMF with a specificity of 95.8% (PMF vs ET; ROC AUC = 0.91). In myelofibrosis, studying follow-ups of WT1 transcript showed that this marker is of interest after allogeneic SCT. These results demonstrate that WT1 overexpression is a simple marker of myelofibrosis in MPN and could be used during patient follow-up.

Warm storage for arc magmas.

Felsic magmatic systems represent the vast majority of volcanic activity that poses a threat to human life. The tempo and magnitude of these eruptions depends on the physical conditions under which magmas are retained within the crust. Recently the case has been made that volcanic reservoirs are rarely molten and only capable of eruption for durations as brief as 1,000 years following magma recharge. If the "cold storage" model is generally applicable, then geophysical detection of melt beneath volcanoes is likely a sign of imminent eruption. However, some arc volcanic centers have been active for tens of thousands of years and show evidence for the continual presence of melt. To address this seeming paradox, zircon geochronology and geochemistry from both the frozen lava and the cogenetic enclaves they host from the Soufrière Volcanic Center (SVC), a long-lived volcanic complex in the Lesser Antilles arc, were integrated to track the preeruptive thermal and chemical history of the magma reservoir. Our results show that the SVC reservoir was likely eruptible for periods of several tens of thousands of years or more with punctuated eruptions during these periods. These conclusions are consistent with results from other arc volcanic reservoirs and suggest that arc magmas are generally stored warm. Thus, the presence of intracrustal melt alone is insufficient as an indicator of imminent eruption, but instead represents the normal state of magma storage underneath dormant volcanoes.