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Le cancer de la prostate est le plus fréquent chez l'homme et, au stade localisé, les schémas d'hypofractionnement de la radiothérapie sont devenus des standards, mais l'absence de risque aggravé de toxicité aiguë et tardive génito-urinaire et gastro-intestinale de l'escalade de dose reste à prouver. La population étudiée comprenait tous les patients pris en charge à l'institut Curie de février 2016 à mars 2018 pour un adénocarcinome prostatique localisé traité par irradiation externe délivrée par un accélérateur linéaire en technique conformationnelle avec modulation d'intensité guidée par l'image à la dose totale de 75 Gy en 30 fractions de 2,5 Gy dans le volume cible prévisionnel comprenant la prostate et les vésicules séminales proximales, et pouvait associer une radiothérapie prophylactique ganglionnaire de 46 Gy en 23 fractions avec la technique de boost intégré. En tout, 166 patients ont été inclus, dont 114 étaient atteints de cancer de risque au moins intermédiaire défavorable (soit 68,7 %). L'âge et le suivi médians étaient de 71,4 ans et 3,96 ans. Cent quarante-neuf patients ont reçu une radiothérapie ganglionnaire (soit 89,8 %). Cent trente et un patients ont reçu une hormonothérapie (soit 78,9 %). Une toxicité génito-urinaire de grade 2 ou plus a été notée en cours de radiothérapie, à 6 mois, 1 an et 5 ans respectivement dans 36,7 %, 8,8 %, 3,1 % et 4,7 % des cas. Deux patients ont souffert à 5 ans d'une toxicité de grade 4 (soit 1,6 %). Une toxicité gastro-intestinale de grade 2 ou plus a été notée en cours de radiothérapie, à 6 mois, 1 an et 5 ans dans respectivement 15,1 %, 1,9 %, 14,6 % et 9,3 % des cas. Parmi ces derniers, huit patients ont souffert d'une toxicité de grade 3 (soit 6,2 %). Il n'y a eu aucune toxicité de grade 4. Les analyses n'ont pas mis en évidence de facteur prédictif de toxicité. Les taux de survie globale, sans progression et spécifique à 5 ans étaient respectivement de 82,4 %, 85,7 % et 93,3 %. La concentration sérique d'antigène spécifique de la prostate et les facteurs de risque cardiovasculaires ont été retrouvés comme facteurs prédictifs d'une dégradation de la survie globale (p = 0,0028 pour les deux). La radiothérapie externe pour un cancer prostatique localisé avec notre schéma modérément hypofractionné avec escalade de dose est bien tolérée. En l'absence de toxicité tardive majorée, l'analyse des modes de rechutes à long terme sera intéressante pour déterminer l'intérêt de cette escalade de dose sur les rechutes locales et à distance. Prostate cancer is the most frequent cancer among men and radiotherapy hypofractionation regimens have become standard treatments for the localized stages, but the absence of increased risk of acute and late genitourinary or gastrointestinal toxicity of the dose escalation still must be demonstrated. The study population included all patients with localized prostatic adenocarcinoma treated at the institut Curie from February 2016 to March 2018 by external radiation delivered by a linear accelerator using an image-guided conformal intensity modulation technique at a total dose of 75 Gy in 30 fractions of 2.5 Gy in the planning target volume that included the prostate and the proximal seminal vesicles, and could be paired with a prophylactic lymph node radiotherapy at 46 Gy in 23 fractions with simultaneous integrated boost. A total of 166 patients were included. Among them, 68.6% were unfavourable intermediate or (very) high risk. The median age and follow-up were 71.4 years and 3.96 years. One hundred and forty-nine patients received prophylactic lymph node radiotherapy (89.8%). One hundred and thirty-one patients received hormonotherapy (78.9%). Genito-urinary toxicity events of grades 2 or above during radiotherapy, at 6 months, 1 year and 5 years were respectively 36.7%, 8.8%, 3.1% and 4.7%. Two patients had late grade 4 toxicity at 5 years (1.6%). Grade 2 gastrointestinal toxicity events during radiotherapy, 6 months, 1 year and 5 years were respectively 15.1%, 1.9%, 14.6% and 9.3%. Of these, eight patients had grade 3 toxicity (6.2%). There was no grade 4 toxicity. Analyses did not reveal any predictive factor for toxicity. The 5-year overall, progression-free, and specific survival rates were respectively 82.4%, 85.7%, and 93.3%. Serum prostate specific antigen concentration and cardiovascular risk factors were found to be predictive factors of deterioration in overall survival (P = 0.0028 for both). External radiotherapy for localized prostatic cancer with our moderately hypofractionated dose escalation regimen is well tolerated. In the absence of increased late toxicity, the analysis of the modes of long-term relapses will be interesting to determine the benefit of this dose escalation on local and distant relapses. [ABSTRACT FROM AUTHOR]

In Belgium, the use of IHC testing has grown in the last decade. However, there is a lack of information on the specific indications for which it is reimbursed. The aim of the study is to offer an overview on the use of diagnostic inmunohistochemistry (IHC) testing and its recent trends. Our analysis is limited to reimbursed use, which in Belgium is restricted to a maximum of 4 different IHC stains per sampling session for diagnostic IHC. Consulted sources included data from the compulsory health insurance, and data extracted from a sample of pathology reports gathered from Belgian laboratories for the year 2019. Over the last 10 years, the use of IHC in Belgium grew from 729 030 stains in 2012 to 1,194,331 in 2019, an increase of 63.8 % while the increase in the number of histological or cytological examinations was 13.3 %. The main stains used in 2019 were H. pylori , Ki-67 and broad spectrum CK, which were used in multiple body sites, reflecting the difficulties to identify specific indications. The gastro-intestinal tract is the body site with the highest number of IHC stains (38.2 % of all stains performed), and the most frequently used stain in gastro intestinal biopsies were H. pylori (43.1 %), and CD3 (6.8 %). This study offers an overview of the most frequent indications for which diagnostic IHC staining is used in Belgium, and reflects the evolving nature of this field, highlighting the importance to increase clarity and improve data collection. • The use of IHC in Belgium increased by 63.8% from 2012 to 2019. • The main stain used in 2019 was Helicobacter Pylori. • The highest number of IHC stains are performed on samples from the gastro-intestinal tract. • This study highlights the importance to increase clarity and improve data collection in the use of IHC staining. [ABSTRACT FROM AUTHOR]

• What is the key question? Which are the most common cancers in the UK cystic fibrosis population and what factors are associated with the incidence of all cancers and in particular gastrointestinal malignancies? • What is the bottom line? The types of cancer in people with CF are varied but reflect those found in the general population. Any cancer and particularly GI cancer appear to be peaking at a younger age, while CFRD is confirmed as a risk factor alongside transplantation. • Why read on? This is the largest study conducted in the UK CF population exploring patterns of cancer incidence and factors associated with it. We observed a high incidence of GI cancers, skin and breast cancers compared to other cancer types. Screening for gastrointestinal cancers could benefit patients at higher risk. To assess cancer incidence in the UK cystic fibrosis (CF) population and determine the associated risk factors, we undertook a nested case-control study of patients with CF, registered with the UK CF Registry. Each case with a first reported cancer between 1999 and 2017 was matched with up to 4 controls: by age (±2-years) and year of cancer diagnosis. Conditional logistic regressions were adjusted for sex, lung function (FEV 1 %), CF related diabetes (CFRD), F508del status, transplant status, DIOS, gastro-oesophageal reflux disease, meconium ileus, Pseudomonas aeruginosa infection, pancreatic insufficiency, proton pump inhibitor (PPI) use, IV antibiotic days and BMI. Results : From 12,886 registered patients, 146 (1.1%) cases of malignancy were identified with 14.3% of cases occurring post solid organ transplant. Site of primary cancer was available for 98 patients: 22% were gastro-intestinal in origin (77% lower, 23% upper GI), 13% skin, 13% breast and 11% lymphomas/leukaemia. In univariable analysis, transplantation increased the odds of reporting any cancer by 2.46 times (95%CI: 1.3-4.6). CFRD also increased the odds of reporting any cancer (OR 2.35; CI: 1.37-4.0) and PPI use (OR 2.0; CI 1.28-3.19). In the multivariable models significant associations with CFRD and transplant remained, while PA infection, PPI use and being overweight showed increased, but statistically insignificant risks. The incidence of GI cancer was strongly associated with CFRD (OR=4.04; 1.47-11.1). Conclusions : We observed a high incidence of lower GI cancers in our cohort which was significantly affected by the presence of CFRD. Screening for gastrointestinal cancers could benefit patients at higher risk. [ABSTRACT FROM AUTHOR]

Pullulan was used as the wall material for microencapsulation of L. plantarum CRD7 by spray drying, while isomalto-oligosaccharides (IMO) was used as prebiotic. Also, the effect of different thermal protectants on survival rate during microencapsulation was evaluated. Taguchi orthogonal array design showed that pullulan at 14 % concentration, IMO at 30 % concentration and whey protein isolate at 20 % rate were the optimized wall material, prebiotic and thermal protectant, respectively for microencapsulation of L. plantarum. FESEM images revealed that the spray-dried encapsulates were fibrous similar to those produce by electrospinning, while fluorescence microscopy ascertained that most of the probiotic cells were alive and intact after microencapsulation. The adsorption-desorption isotherm was of Type II and the encapsulate had specific surface area of 1.92 m2/g and mean pore diameter of 15.12 nm. The typical amide II and III bands of the bacterial proteins were absent in the FTIR spectra, suggestive of adequate encapsulation. DSC thermogram showed shifting of melting peaks to wider temperature range due to interactions between the probiotic and wall materials. IMO at 30 % (w /w) along with WPI at 20 % concentration provided the highest storage stability and the lowest rate of cell death of L. plantarum after microencapsulation. Acid and bile salt tolerance results confirmed that microencapsulated L. plantarum could sustain the harsh GI conditions with >7.5 log CFU/g viability. After microencapsulation, L. plantarum also possessed the ability to ferment milk into curd with pH of 4.62. [ABSTRACT FROM AUTHOR]

Gastrointestinal nematodes (GIN) have enormous global impacts in humans, wildlife and grazing livestock. Within grazing livestock, sheep are of particular global importance and the economics and sustainability of sheep production are greatly constrained by GIN infections. Natural infections are composed of co-infections with multiple species, and while some past work suggests species can interact negatively with one another within the same host, there is wide variation in reported patterns. Here, we undertook a systematic literature search and meta-analysis of experimental GIN co-infections of sheep to determine whether these experimental studies support the hypothesis of antagonistic interactions between different co-infecting GIN, and test whether aspects of parasite biology or experimental design influence the observed effects. A systematic search of the literature yielded 4848 studies, within which, we identified 19 experimental sheep studies comparing post-mortem worm counts across two co-infecting GIN species. Meta-analysis of 67 effects obtained from these studies provides strong evidence for interactions between GIN species. There was wide variation in the strength and direction of these interactions, but the global effect was significantly antagonistic. On average, there was a decrease in the number of worms of one species when a co-infecting species was also present, relative to a mono-infection with that species alone. This effect was dependent on the infectious dose and was rapidly lost after anthelmintic treatment, suggesting that live worms are required for the effect to occur. Individual parasite species varied in the extent to which they both exerted, and were subject to, these interspecies interactions, and these differences are more complex than simply co-localisation within the gastrointestinal tract. Antagonistic interactions between co-infecting GIN may feedback into their epidemiology as well as potentially affecting the clinical impacts of infection. Furthermore, the consequences of these interactions may be heightened when clinical interventions affect only one species within the co-infecting network. Whilst it was not possible to identify the causes of variation between GIN species in the impact of co-infection, these findings point to new avenues for epidemiological, clinical and mechanistic research on GIN co-infections. [Display omitted] • Co-infecting gastrointestinal nematodes interact antagonistically. • This competition between co-infecting helminths is parasite dose dependent. • Interactions are lost after anthelmintics, suggesting live parasites are required. • Parasite species vary in how strongly they influence a concomitant infection. • Parasite species vary in how susceptible they are to co-infecting parasites. [ABSTRACT FROM AUTHOR]

The latest WHO classification of the female genital tract tumors introduces a new type of carcinoma: the primary gastric-type (or gastro-intestinal type) carcinoma of the endometrium. This type of neoplasm tends to have a poor outcome, making its correct diagnostic important. As little is known about this entity and given its quite challenging diagnosis, we aim to review existing data about it and propose a practical diagnostic approach. There are currently 11 cases published in 8 articles fitting the precise definition of a primary gastric-type carcinoma of the endometrium. Three main differential diagnoses must be excluded before considering this tumor: endometrioid adenocarcinoma with mucinous (Müllerian-type) differentiation, endocervical primary, and gastro-intestinal primary. Morphological aspects of this tumor can be heterogeneous and confusing; in this context, immunochemistry can be helpful to highlight the gastric or intestinal differentiation, but also to eliminate a mucinous endometrioid adenocarcinoma of Müllerian-type, by the constant negativity of estrogen receptors. A metastasis of a primary gastro-intestinal tract carcinoma must also be excluded by clinical, endoscopic and imaging work-up. Finally, an endometrial extension of a primary endocervical gastric-type carcinoma should be ruled out by complete sampling of the cervix. Intestinal type endocervical adenocarcinoma is easier to eliminate since this is an HPV-associated neoplasm. [ABSTRACT FROM AUTHOR]

The significant decrease of live bacteria during passage of the upper gastrointestinal system is an important drawback for probiotic functional food. Microencapsulation is frequently reported to increase bacterial survival in simulated gastric juice (SGJ) but confirmatory in vivo studies are lacking. The present study aimed to characterize protective effects of milk-protein-based microcapsules in vitro as well as in mice as model consumer. Sodium caseinate (SC) and newly developed, SGJ-resistant fat SC (FSC) capsules significantly increased survival of two Lactobacillus strains in SGJ. In contrast, neither SC nor FSC microcapsules increased bacterial survival in the murine gastrointestinal system 3 or 24 h after oral uptake. This lack of protection is presumably due to rapid digestion of the microcapsules in the murine stomach. The present work demonstrates that positive results from frequently applied simple in vitro assays cannot be extrapolated to living organisms and highlights the importance of in vivo analyses. [ABSTRACT FROM AUTHOR]

Abstract: Monepantel is the first compound from the recently discovered amino-acetonitrile derivative (AAD) class of anthelmintics to be developed for use in sheep. Nine dose confirmation studies were conducted in Australia, New Zealand and Switzerland to confirm the minimum therapeutic oral dose of monepantel to control fourth stage (L4) gastro-intestinal nematode larvae in sheep (target species were Haemonchus contortus, Teladorsagia (Ostertagia) circumcincta, Teladorsagia trifurcata, Trichostrongylus axei, Trichostrongylus colubriformis, Trichostrongylus vitrinus, Cooperia curticei, Cooperia oncophora, Nematodirus battus, Nematodirus filicollis, Nematodirus spathiger, Chabertia ovina and Oesophagostomum venulosum). In each study, sheep infected with a defined selection of the target nematodes were treated with 2.5mg monepantel/kg liveweight. Following euthanasia and worm counting, efficacy was calculated against worm counts from untreated control groups. The results demonstrate high (95<100%) efficacy of monepantel when administered orally to sheep at 2.5mg/kg for most species tested. Efficacy levels against N. spathiger and O. venulosum were variable and failed to meet the required regulatory standard (≥90%) in some studies. Efficacy was demonstrated against L4 stages of nematodes known to be resistant to either benzimidazole and/or levamisole anthelmintics (macrocyclic lactone resistant isolates were not available for testing). The broad-spectrum activity of monepantel against L4 larvae of common gastro-intestinal nematodes in sheep and its favorable safety profile represents a significant advance in the treatment of parasitic gastro-enteritis in this animal species. No adverse effects related to treatment with monepantel were observed. [Copyright &y& Elsevier]

Abstract: Monepantel is the first compound from the recently discovered amino-acetonitrile derivative (AAD) class of anthelmintics to be developed for use in sheep. Three dose determination studies were conducted in Australia and Switzerland to identify the minimum therapeutic dose of monepantel when formulated for the oral treatment of sheep to control fourth stage (L4) gastro-intestinal nematode larvae. In each study, sheep infected with the target nematodes (selected from Haemonchus contortus, Teladorsagia (Ostertagia) circumcincta, Teladorsagia trifurcata, Trichostrongylus axei, Trichostrongylus colubriformis, Trichostrongylus vitrinus, Cooperia curticei, Cooperia oncophora, Nematodirus battus, Nematodirus filicollis, Nematodirus spathiger, Chabertia ovina and Oesophagostomum venulosum) were treated with either 1.25, 2.5 or 5.0mg monepantel/kg liveweight. Following euthanasia and worm counting, efficacy was calculated against worm counts from untreated control groups. Monepantel proved highly effective at 2.5 and 5.0mg/kg, but was only moderately effective against some nematode species (L4 stage) at 1.25mg/kg. The results also confirmed that monepantel will effectively control L4 stages of nematodes resistant to at least some of the currently available broad-spectrum anthelmintic classes (macrocyclic lactone resistant strains were not included in the studies). It was concluded that 2.5mg/kg would be a suitable minimum dose rate for a commercial product. No adverse events related to treatment with monepantel were detected. [Copyright &y& Elsevier]

Summary: The surgical treatment of neonates has enjoyed rapid development during the last 50 years. Neonatal surgery has now become an independent branch of general surgery, which requires the expertise of dedicated paediatric surgeons. Much of the development of neonatal surgery is due to the close collaboration between paediatric surgeons, neonatologists, anaesthetists, pathologists, radiologists, biochemists, and nurses. There has been a steady improvement in the outcome of most neonatal diseases requiring surgery. For example at Great Ormond Street Hospital for Children, London, the mortality for the most common congenital intestinal obstructions has declined from 50% in the 1950s and 1960s to 25% in the 1960s and 1970s to a current mortality of less than 5%. The reasons for this improvement can be ascribed to a better understanding of the physiology of surgical neonates, to the advances in fluid management, nutrition, mechanical ventilation, and not least to refinements in surgical techniques. There is still considerable work to be done to improve the survival of neonates with severe conditions such as necrotizing enterocolitis (NEC). Surgery of the gastro-intestinal tract is required for congenital abnormalities and acquired lesions. In this article the authors focus on the most common congenital anomalies of the gastro-intestinal tract requiring surgery. In addition they discuss two acquired conditions requiring surgery in neonates: NEC and hypertrophic pyloric stenosis. It is beyond the scope of this article to discuss anomalies of the abdominal wall, gastro-oesophageal reflux, and anomalies of the pancreato-biliary system. [Copyright &y& Elsevier]

Summary: Introduction: Oral nutritional supplements may have a role in the management of weight loss in patients with cancer. Information on preference for different types of nutritional supplements and the influence of taste changes and chemotherapy is limited. Aims and methods: This study aimed, in patients with gastrointestinal (GI) cancer, to determine the short-term preference for commonly used nutritional supplements compared with controls, to examine whether preference is altered by chemotherapy and to assess the reproducibility of taste assessments conducted using a Visual Analogue Scale (VAS). Patients with GI cancer and controls were asked to rate the acceptability of three oral nutritional supplements on a VAS before starting chemotherapy and after 6 weeks of chemotherapy. Supplements were presented in a random order in sealed containers and subjects were blinded to the type of product. One supplement was repeated at random within each set (four cups) to assess the reproducibility of responses. Results: Sixty patients and 63 controls were included in the study, 47 patients and 47 controls were available for follow-up. Before the start of chemotherapy, patients had a higher mean preference for Calshake (5.9cm) than Ensure plus (5.1cm) and Fortijuce (3.2cm) ( and ). Calshake was the most preferred supplement in the control group (mean 6.6cm), with no significant differences in preferences between patients and controls. There were no changes in preference for patients after 6 weeks of chemotherapy. The results for the control group similarly showed no change after 6 weeks. No significant differences were found between scores assigned to the supplement repeated in the random order for any product at either timepoint. Discussion: Patients with GI cancers prefer the taste of fresh milk-based supplements and short-term preferences are not changed by chemotherapy. Preferences are similar between patients with GI cancers and people without cancer. A VAS is a reliable tool to assess taste preference. Further studies are needed to assess the patient compliance over longer periods and the reasons for non-compliance with prescriptions for nutritional supplements. [Copyright &y& Elsevier]

The purpose of this study was to investigate the role of 24 h pH monitoring for the diagnosis of otolaryngologic including rhinologic manifestations of gastro-esophageal reflux (GER) in children and if possible to correlate the results with the efficacy of medical treatment.This is a retrospective study of 72 children from January 1997 to December 1999. The children were separated into three groups according to the main symptoms (although association of symptoms was frequent): rhinologic (n=28), laryngotracheal (n=28) and pharyngeal-otologic (n=16).With the classical gastroenterologic criterion (≥4.2% of total time at pH < 4), the pH monitoring was positive in 56% of the patients. However, this criterion does not seem to be sensitive for otolaryngologic gastro-esophageal reflux disease (GERD) because multiple daytime short reflux episodes are often involved. Indeed, the pH monitoring was positive in 75% of the patients (82% in the rhinologic group) when a number of 40 episodes in 24 h was also taken into account. The success rate of medical treatment was about 80% in case of positive pH recording. This study underlines that GER is an important factor in pediatric otolaryngologic diseases. [Copyright &y& Elsevier]