Prognostic impact of epidermal growth factor receptor (EGFR) expression on loco-regional recurrence after preoperative radiotherapy in rectal cancer

BACKGROUND: Epidermal growth factor receptor (EGFR) represents a major target for current radiosensitizing strategies. We wished to ascertain whether a correlation exists between the expression of EGFR and treatment outcome in a group of patients with rectal adenocarcinoma who had undergone preoperative radiotherapy (RT). METHODS: Within a six-year period, 138 patients underwent preoperative radiotherapy and curative surgery for rectal cancer (UICC stages II-III) at our institute. Among them, 77 pretherapeutic tumor biopsies were available for semi-quantitative immunohistochemical investigation evaluating the intensity and the number (extent) of tumor stained cells. Statistical analyses included Cox regression for calculating risk ratios of survival endpoints and logistic regression for determining odds ratios for the development of loco-regional recurrences. RESULTS: Median age was 64 years (range: 30–88). Initial staging showed 75% and 25% stage II and III tumors, respectively. RT consisted of 44-Gy pelvic irradiation in 2-Gy fractions using 18-MV photons. In 25 very low-rectal-cancer patients the primary tumor received a boost dose of up to 16 Gy for a sphincter-preservation approach. Concomitant chemotherapy was used in 17% of the cases. All patients underwent complete total mesorectal resection. Positive staining (EGFR+) was observed in 43 patients (56%). Median follow-up was 36 months (range: 6–86). Locoregional recurrence rates were 7 and 20% for EGFR extent inferior and superior to 25%, respectively. The corresponding locoregional recurrence-free survival rate at two years was 94% (95% confidence interval, CI, 92–98%) and 84% (CI 95%, 58–95%), respectively (P = 0.06). Multivariate analyses showed a significant correlation between the rate of loco-regional recurrence and three parameters: EGFR extent superior to 25% (hazard ratio = 7.18, CI 95%, 1.17–46, P = 0.037), rectal resection with microscopic residue (hazard ratio = 6.92, CI 95%, 1.18–40.41, P = 0.032), and a total dose of 44 Gy (hazard ratio = 5.78, CI 95%, 1.04–32.05, P = 0.045). CONCLUSION: EGFR expression impacts on loco-regional recurrence. Knowledge of expression of EGFR in rectal cancer could contribute to the identification of patients with an increased risk of recurrences, and to the prediction of prognosis

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Impact of invasive alien plants on ecosystem functionning in Belgium

Les invasions biologiques sont une cause majeure de perte de biodiversité à l’échelle mondiale. L’impact direct des espèces exotiques envahissantes (EEE) sur la structure et la composition des communautés a été bien documenté. Par contre, leur impact sur le fonctionnement des écosystèmes a été comparativement moins étudié. Dans le présent travail, j’ai mesuré sur le terrain et en conditions expérimentales l’impact de 7 espèces de plantes exotiques particulièrement envahissantes en Europe sur les propriétés chimiques du sol, sur la productivité et sur le stock d’éléments minéraux dans la biomasse. Malgré la diversité des groupes fonctionnels considérés dans notre échantillon (des espèces annuelles aux arbres), des impacts récurrents ont pu être mis en évidence. Les EEE ont toujours une biomasse et une productivité supérieures à celles de la végétation qu’elles envahissent. Il en va de même pour le stock d’éléments minéraux dans la biomasse aérienne. En ce qui concerne le sol, les traits fonctionnels des espèces ne permettent pas de prédire la direction et l’amplitude des impacts. Par contre, ces impacts sur le sol se sont révélés partiellement prévisibles en fonction des conditions écologiques initiales (contexte pédologique). La disponibilité des cations et du P et la concentration en C et N organiques augmentent suite à l’invasion dans les sites initialement pauvres alors que ces mêmes paramètres baissent dans les sites plus eutrophes au départ. Les EEE entraînent, dans une certaine mesure, une homogénéisation des conditions écologiques dans les écosystèmes envahis. <p>Dans un deuxième temps, je me suis attaché à identifier les mécanismes de l’impact de Fallopia japonica sur le cycle de l’azote. Cette espèce, perenne rhizomateuse, adopte une gestion très conservatrice de l’azote en retransloquant jusqu’à 80 % de l’azote des tiges et des feuilles vers le système racinaire en automne avant l’abscission des feuilles. La litière restituée est, de ce fait, pauvre en azote. Ce paramètre, combiné à une teneur élevée en lignine, explique sa faible vitesse de décomposition par rapport à celle de la végétation non envahie. Une grande partie de l’azote de l’écosystème tourne donc en cycle quasi fermé entre les organes de réserve et les parties aériennes de la plante, tandis que l’azote restant est en grande partie bloqué dans la nécromasse de la plante et est donc non disponible pour les espèces concurrentes indigènes. Ce mécanisme explique, sans doute, en partie le succès invasif de l’espèce.<p><p>A l’avenir, les implications des impacts sur le sol en terme de restauration des communautés devront être étudiées. L’hypothèse d’une influence positive de ces impacts sur l’aptitude compétitive des espèces envahissantes devra être testée. Enfin, une étude plus fonctionnelle des impacts de ces espèces dans des sites contrastés devrait permettre d’identifier les mécanismes impliqués./Biological invasions are a major cause of biodiversity loss worldwide. The direct impact of alien invasive species (AIS) on community structure and composition has been well documented. On the other hand, their impact on ecosystem functioning has been comparatively less studied. In this work, I measured, on the field and in experimental conditions, the impact of 7 highly invasive alien plant species in Europe on soil chemical properties, biomass and aboveground nutrient stock. Despite the high diversity in considered functional groups (from annuals to trees), recurring impacts have been found. AIS had always higher biomass and aboveground nutrient stocks than invaded resident vegetation. Concerning soil, species functional traits did not allow us to predict impact direction and intensity. On the other hand, impacts on soil were partially predictable based on initial ecological conditions (pedologic context). Thus, cations and P availability and organic C and N concentrations increased in initially poor sites and decreased in eutrophic ones. AIS tend to homogenize soil properties across invaded landscapes.<p>In a second part, i tried to identify the mechanisms of the impacts of Fallopia japonica on N cycling. This perrennial rhizomatous species manage N in a very conservative way. About 80 % of aboveground N is translocated to rhizomes before leaves abscission. The litter is therefore poor in N. This parameter combined with a high lignin concentration explains its slow decomposition rate compared to that of uninvaded vegetation. A big part of the ecosystem N is engaged in a nearly closed cycle between above and belowground organs while the remaining N is blocked in the necromass and is thus not available for the indigenous competitors. This mechanism probably explains the invasive success of this species.<p><p>In the future, the implications of soil properties modifications in terms of community restoration should be studied. The hypothesis of a positive influence of these modifications on the competitive ability of AIS should be tested. At last, a functional study of these soil impacts in contrasted sites should allow us to identify the implied mechanisms.<p>Doctorat en Sciencesinfo:eu-repo/semantics/nonPublishe

Towards a KUBC homogenization for architected materials by experimental process

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Towards a KUBC homogenization for architected materials by experimental process

International audienc

Conception d'un dispositif d'homogénéisation expérimentale par KUBC

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