Artificial intelligence in digestive endoscopy: recent advances.

PURPOSE OF REVIEW: With the incessant advances in information technology and its implications in all domains of our life, artificial intelligence (AI) started to emerge as a need for better machine performance. How it can help endoscopists and what are the areas of interest in improving both diagnostic and therapeutic endoscopy in each part of the gastrointestinal (GI) tract. What are the recent benefits and clinical usefulness of this new technology in daily endoscopic practice. RECENT FINDINGS: The two main AI systems categories are computer-assisted detection 'CADe' for lesion detection and computer-assisted diagnosis 'CADx' for optical biopsy and lesion characterization. Multiple softwares are now implemented in endoscopy practice. Other AI systems offer therapeutic assistance such as lesion delineation for complete endoscopic resection or prediction of possible lymphanode after endoscopic treatment. Quality assurance is the coming step with complete monitoring of high-quality colonoscopy. In all cases it is a computer-aid endoscopy as the overall result rely on the physician. Video capsule endoscopy is the unique example were the computer conduct the device, store multiple images, and perform accurate diagnosis. SUMMARY: AI is a breakthrough in digestive endoscopy. Screening gastric and colonic cancer detection should be improved especially outside of expert's centers. Prospective and multicenter trials are mandatory before introducing new software in clinical practice.

Further delineation of the NTHL1 associated syndrome: A report from the French Oncogenetic Consortium.

Biallelic pathogenic variants in the NTHL1 (Nth like DNA glycosylase 1) gene cause a recently identified autosomal recessive hereditary cancer syndrome predisposing to adenomatous polyposis and colorectal cancer. Half of biallelic carriers also display multiple colonic or extra-colonic primary tumors, mainly breast, endometrium, urothelium, and brain tumors. Published data designate NTHL1 as an important contributor to hereditary cancers but also underline the scarcity of available informations. Thanks to the French oncogenetic consortium (Groupe Génétique et Cancer), we collected NTHL1 variants from 7765 patients attending for hereditary colorectal cancer or polyposis (n = 3936) or other hereditary cancers (n = 3829). Here, we describe 10 patients with pathogenic biallelic NTHL1 germline variants, that is, the second largest NTHL1 series. All carriers were from the "colorectal cancer or polyposis" series. All nine biallelic carriers who underwent colonoscopy presented adenomatous polyps. For digestive cancers, average age at diagnosis was 56.2 and we reported colorectal, duodenal, caecal, and pancreatic cancers. Extra-digestive malignancies included sarcoma, basal cell carcinoma, breast cancer, urothelial carcinoma, and melanoma. Although tumor risks remain to be precisely defined, these novel data support NTHL1 inclusion in diagnostic panel testing. Colonic surveillance should be conducted based on MUTYH recommendations while extra-colonic surveillance has to be defined.

When the average hides the risk of Bt-corn pollen on non-target Lepidoptera: Application to Aglais io in Catalonia.

Field cultivation of Genetically Modified (GM) Bt-plants has a potential environmental risk toward non-target Lepidoptera (NTLs) larvae through the consumption of Bt-maize pollen. The Bt-maize Cry protein targeting Lepidoptera species detrimental to the crop is also expressed in pollen which is dispersed by wind and can thus reach habitats of NTLs. To better assess the current ecological risk of Bt-maize at landscape scales, we developed a spatially-explicit exposure-hazard model considering (i) the dynamics of pollen dispersal obtained by convolving GM plants emission with a dispersal kernel and (ii) a toxicokinetic-toxicodynamic (TKTD) model accounting for the impact of toxin ingestion on individual lethal effects. We simulated the model using real landscape observations in Catalonia (Spain): GM-maize locations, flowering dates, rainfall time series and larvae emergence date of the European peacock butterfly Aglais io. While in average, the additional mortality appears to be negligible, we show significant additional mortality at sub-population level, with for instance a mortality higher than 40% within the 10m for the 10% most Bt-sensitive individuals. Also, using Pareto optimality we capture the best trade-off between isolation distance and additional mortality: up to 50 m are required to significantly buffer Bt-pollen impact on NTLs survival at the individual level. Our study clears up the narrow line between diverging conclusions: those claiming no risk by only looking at the average regional effect of Bt on NTLs survival and those pointing out a significant threaten when considering the variability of individuals mortality.

Use of rapid reading software to reduce capsule endoscopy reading times while maintaining accuracy.

BACKGROUNDS AND AIMS: A typical capsule endoscopy (CE) case generates tens of thousands of images, with abnormalities often confined to a just few frames. Omni Mode is a novel EndoCapsule software algorithm (Olympus, Tokyo, Japan) that proposes to intelligently remove duplicate images while maintaining accuracy in lesion detection. METHODS: This prospective multicenter study took place across 9 European centers. Consecutive, unselected CE cases were read conventionally in normal mode, with every captured frame reviewed. Cases were subsequently anonymized and randomly allocated to another center where they were read using Omni Mode. Detected lesions and reading times were recorded, with findings compared between both viewing modes. The clinical significance of lesions was described according to the P classification (P0, P1, and P2). Where a discrepancy in lesion detection in either mode was found, expert blinded review at a consensus meeting was undertaken. RESULTS: The patient population undergoing CE had a mean age of 49.5 years (range, 18-91), with the investigation of anemia or GI bleeding accounting for 71.8% of cases. The average small-bowel transit time was 4 hours, 26 minutes. The mean reading time in normal mode was 42.5 minutes. The use of Omni Mode was significantly faster (P < .0001), with an average time saving of 24.6 minutes (95% confidence interval, 22.8-26.9). The 2127 lesions were identified and classified according to the P classification as P0 (1234), P1 (656), and P2 (237). Lesions were identified using both reading modes in 40% (n = 936), and 1186 lesions were identified by either normal or Omni Mode alone. Normal mode interpretation was associated with 647 lesions being missed, giving an accuracy of .70. Omni Mode interpretation led to 539 lesions being missed, with an accuracy of .75. There was no significant difference in clinical conclusions made between either reading mode. CONCLUSIONS: This study shows that CE reading times can be reduced by an average of 40%, without any reduction in clinical accuracy.

Recommendations for the Operation of Endoscopy Centers in the setting of the COVID-19 pandemic - World Endoscopy Organization guidance document.

Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) is the etiologic agent causing the disease Corona Virus Disease 19 (COVID-19), resulting in a worldwide pandemic. Non-emergent endoscopy services have been disrupted as incidence and hospitalizations were rising. It is anticipated that the peak incidence may be leveling off in many parts of the world, but there is a concern for resurgence of the virus activity. Thus, it is important for endoscopy units to have plans in place during peak times of the epidemic and when resuming endoscopic services as the pandemic wanes. The global endoscopy community is faced with the challenge of providing care during this time. The WEO-COVID guidance task force has provided this resource document based on the current evidence and consensus opinion. These World Endoscopy Organization (WEO) recommendations are meant to guide endoscopists worldwide, should be interpreted in light of specific clinical conditions and resource availability and may not apply in all situations. This guidance document does not supersede the need to check for all local regulations and legislations.

Alu element insertion in the MLH1 exon 6 coding sequence as a mutation predisposing to Lynch syndrome.

Lynch syndrome (LS) is the most frequent cause of hereditary colorectal cancer. A subset of patients with a history of LS shows no causal germline pathogenic alteration and are identified as having Lynch-like syndrome (LLS). Alu retrotransposons are the most abundant mobile DNA sequences in the human genome and have been associated with numerous human cancers by either disrupting coding regions or altering epigenetic modifications or splicing signals. We report a family first classified as having LLS by Sanger sequencing analysis. Next-generation sequencing (NGS) analysis identified an AluY5a insertion in MLH1 exon 6 that led to exon skipping. This splicing alteration inducing a pathogenic frameshift was found in patients who developed colorectal adenocarcinomas. Retroelement insertion might thus be an important but underestimated mechanism of cancer genetics that could be systematically tested in patients with a phenotype suggesting LS to accurately assess family risk and surveillance approaches.

Assessing the durability and efficiency of landscape-based strategies to deploy plant resistance to pathogens.

Genetically-controlled plant resistance can reduce the damage caused by pathogens. However, pathogens have the ability to evolve and overcome such resistance. This often occurs quickly after resistance is deployed, resulting in significant crop losses and a continuing need to develop new resistant cultivars. To tackle this issue, several strategies have been proposed to constrain the evolution of pathogen populations and thus increase genetic resistance durability. These strategies mainly rely on varying different combinations of resistance sources across time (crop rotations) and space. The spatial scale of deployment can vary from multiple resistance sources occurring in a single cultivar (pyramiding), in different cultivars within the same field (cultivar mixtures) or in different fields (mosaics). However, experimental comparison of the efficiency (i.e. ability to reduce disease impact) and durability (i.e. ability to limit pathogen evolution and delay resistance breakdown) of landscape-scale deployment strategies presents major logistical challenges. Therefore, we developed a spatially explicit stochastic model able to assess the epidemiological and evolutionary outcomes of the four major deployment options described above, including both qualitative resistance (i.e. major genes) and quantitative resistance traits against several components of pathogen aggressiveness: infection rate, latent period duration, propagule production rate, and infectious period duration. This model, implemented in the R package landsepi, provides a new and useful tool to assess the performance of a wide range of deployment options, and helps investigate the effect of landscape, epidemiological and evolutionary parameters. This article describes the model and its parameterisation for rust diseases of cereal crops, caused by fungi of the genus Puccinia. To illustrate the model, we use it to assess the epidemiological and evolutionary potential of the combination of a major gene and different traits of quantitative resistance. The comparison of the four major deployment strategies described above will be the objective of future studies.

Psychosocial and clinical factors of probands impacting intrafamilial disclosure and uptake of genetic testing among families with BRCA1/2 or MMR gene mutations.

OBJECTIVE: Intrafamilial disclosure of hereditary cancer predisposition in BRCA1/2 and mismatch repair gene (MMR) syndromes allows appropriate prevention strategies in at-risk relatives. We previously showed in a nationwide study that the uptake of genetic targeted testing (GTT) in these families was only 30%. We aimed to identify the clinical and psychosocial factors affecting the probands' intrafamilial disclosure and relatives' uptake of GTT in BRCA1/2 or MMR syndromes. METHODS: We assessed clinical variables, family history, and psychosocial variables of probands (depressive symptoms, anxiety, alexithymia, optimism, coping, family relationship, perception of cancer risks, and of hereditary transmission), together with disclosure and uptake of GTT within 103 French BRCA1/2 or MMR families. RESULTS: Among relatives eligible for GTT, 68% were informed of the predisposition, and 37% underwent GTT, according to probands' reports. Intrafamilial disclosure was inversely associated with the degree of kinship (P < .01). In multivariable analysis, disclosure increased with time since probands' genetic diagnosis (P < .01) and probands' feeling of family cohesion (0.01). GTT uptake increased with probands' depressive symptoms (0.02) and decreased with probands' perception of cancer risks (0.03). BRCA1/2 and MMR groups did not differ concerning family information and GTT uptake. CONCLUSIONS: This study identified factors affecting disclosure to relatives and GTT uptake in BRCA1/2 and MMR syndromes and gives new insights to improve probands' follow-up and intrafamilial sharing of genetic information.

A Spatio-Temporal Exposure-Hazard Model for Assessing Biological Risk and Impact.

We developed a simulation model for quantifying the spatio-temporal distribution of contaminants (e.g., xenobiotics) and assessing the risk of exposed populations at the landscape level. The model is a spatio-temporal exposure-hazard model based on (i) tools of stochastic geometry (marked polygon and point processes) for structuring the landscape and describing the exposed individuals, (ii) a dispersal kernel describing the dissemination of contaminants from polygon sources, and (iii) an (eco)toxicological equation describing the toxicokinetics and dynamics of contaminants in affected individuals. The model was implemented in the briskaR package (biological risk assessment with R) of the R software. This article presents the model background, the use of the package in an illustrative example, namely, the effect of genetically modified maize pollen on nontarget Lepidoptera, and typical comparisons of landscape configurations that can be carried out with our model (different configurations lead to different mortality rates in the treated example). In real case studies, parameters and parametric functions encountered in the model will have to be precisely specified to obtain realistic measures of risk and impact and accurate comparisons of landscape configurations. Our modeling framework could be applied to study other risks related to agriculture, for instance, pathogen spread in crops or livestock, and could be adapted to cope with other hazards such as toxic emissions from industrial areas having health effects on surrounding populations. Moreover, the R package has the potential to help risk managers in running quantitative risk assessments and testing management strategies.

Tree, sex and size: Ecological determinants of male vs. female fecundity in three Fagus sylvatica stands.

Interindividual variation in fecundities has major consequences on population evolutionary potential, through genetic drift and selection. Using two spatially explicit mating models that analyse the genotypes of seeds and seedlings, we investigated the variation of male and female fecundities within and among three European beech (Fagus sylvatica) stands situated along an altitudinal gradient. Female and male individual fecundity distributions were both skewed in this monoecious species, and we found a higher variance in female as compared to male fecundities. Both female and male fecundities increased with tree size and decreased with density and competition in the neighbourhood, the details of these effects suggesting sex-specific strategies to deal with the impact of limited resource on fecundity. The studied populations were functionally male-biased. Among-individual variations in functional gender were not driven by tree size but by density and competition in the neighbourhood. Femaleness decreased under limited resource availability, an expected consequence of the higher cost of female reproduction. Considering the variation of gene flow and genetic drift across elevation, our results suggest that the adaptive potential could be enhanced by low genetic drift at low elevation, and by high pollen-mediated gene flow at high elevation. Finally, this study predicts a more efficient response to selection for traits related to male vs. female fitness, for a given selection intensity.

Reprocessing of flexible endoscopes and endoscopic accessories used in gastrointestinal endoscopy: Position Statement of the European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Gastroenterology Nurses and Associates (ESGENA) - Update 2018.

This Position Statement from the European Society of Gastrointestinal Endoscopy (ESGE) and the European Society of Gastroenterology Nurses and Associates (ESGENA) sets standards for the reprocessing of flexible endoscopes and endoscopic devices used in gastroenterology. An expert working group of gastroenterologists, endoscopy nurses, chemists, microbiologists, and industry representatives provides updated recommendations on all aspects of reprocessing in order to maintain hygiene and infection control.

Chapter 7. The Contributions of the ESPGHAN Committees on Nutrition to Paediatric Nutrition.

The first Committee on Nutrition (CoN) was founded in 1974. Two years later nutrition (N) was added to the society's name, which then became ESPGAN. The Committee systematised compositional and quality criteria for breast milk substitutes and food for special medical purposes, the first of many examples on how recommendations and comments published by the Committees on Nutrition (CsoN) were adopted by the European Economic Community, later the European Union and also influenced the World Health Organization/Food and Agriculture Organization of the United Nations Codex standards. A second CoN focusing on preterm infants was established in 1979 and its recommendations on nutrition of these infants were widely implemented. The third and standing CoN, established 1986, started to organise high-quality symposia at the annual meetings appreciating the need to enhance the expertise in nutritional research. From 1991 the CoN has organised Summer Schools in paediatric nutrition for young colleagues further emphasising its educational interest and more recently an annual, more specialised Nutrition Masterclass. Successively the interest of the CoN has expanded to other areas, such as highlighting dilemmas and uncertainties in the field of nutrition including the design, choice of outcomes and statistical analysis of trials in infant nutrition. The work of the CsoN have had great impact on paediatric nutrition and the committee will continue its important role by writing commentaries and systematic reviews and revising guidelines when required to inform and stimulate discussion among colleagues as well as stimulate training in paediatric nutrition by organising workshops and scientific meetings, training courses, and other approaches, and by interaction with other expert groups.

Chapter 2. ESPGHAN: 50 Years Memories-The Early Years.

Thirty-six founding members from Europe were present in 1968, when the European Society of Paediatric Gastroenterology (ESGA) had its first meeting in Paris. The aim was to create a forum for presentations and discussions of research activities in paediatric gastroenterology in Europe. At the second meeting of ESGA 1969 in Interlaken, an important landmark was set for all gastroenterologists in the world. In this conference, the first ever criteria for "the Diagnosis of Coeliac Disease" (CD) were established. In 1990, the revised criteria for the diagnosis of CD were published. After the introduction of new noninvasive techniques, like tissue transglutaminase 2-antibodies and the HLADQ2/HLADQ8 determinations in blood, "new" criteria for the diagnosis of CD were published in 2012 by the European society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). Close collaboration of ESPGHAN and the North American Society of Paediatric Gastroenterology, Hepatology and Nutrition led to mutual meetings. The first combined meeting was 1978 in Paris, followed by meetings in New York, Amsterdam, Houston, and last in Toulouse. The first World Congress of Paediatric Gastroenterology took place in Boston 2000 followed by congresses in Paris, Iguazu, Taipeh, and Toronto. The creation of specialised committees (Nutrition Committees, GI-Committee, and Hepatology-Committee) enabled the society to elaborate numerous guidelines for standards in the diagnosis and treatment of diseases within the subspecialties. The Journal of Paediatric Gastroenterology and Nutrition, as organ of ESPGHAN and the North American Society of Paediatric Gastroenterology, Hepatology and Nutrition since 1991, serves as the voice for these worldwide accepted guidelines. Growing educational activities with summer schools, the Young Investigator Forum and the creation of working groups have distributed our current knowledge among the younger generation and led to fruitful reports, guidelines, and syllabus. In 1992, ESPGHAN was 1 of the founding 7 members of the United European Gastroenterology Federation (UEGF), which developed into a successful organisation for gastroenterology in Europe. This year we celebrate the 50th anniversary of ESPGHAN at our annual Meeting in Geneva.

Chapter 8. 50 Years of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN): Captivating Witness Reports of a Success Story.

Since the conception of an idea of a few paediatric gastroenterologists in Europe to create a society for Paediatric Gastroenterology in 1967, and its foundation in 1968, half a century has passed. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) now celebrates its 50th anniversary and its utmost success in combining clinical and scientific expertise in the fields of paediatric gastroenterology, haepatology, and nutrition. To describe this success story 14 of the still living presidents of ESPGHAN recount their impressions of the steady growth of ESPGHAN with all the historical facets from their own points of view. This historical view of ESPGHAN over the last 5 decades provides personal accounts of the development of all activities and creations of this great European Society. The Society started as a small family of experts in the field into a global working open society involved in a large variety of activities within the subspecialties, becoming a leading organisation in Europe and beyond. This unique view gives also a wonderful insight into the famous clinicians and researchers from all over Europe who have helped in the growth and development of ESPGHAN. By describing all these activities and collaborations it becomes clear that this astonishing pan-European enterprise was achieved by people who put considerable effort and time into the development of this society. Their statements serve as a historical source and reference for future evaluation of the first 50 years of ESPGHAN. In depicting different time episodes, and by assembling all the historical pieces of a puzzle together, the statements help to illustrate how a highly structured society such as ESPGHAN has evolved over the last 50 years, for what it stands for today and what is to be expected in the future.

Early onset breast cancer: differences in risk factors, tumor phenotype, and genotype between North African and South European women.

PURPOSE: This report compares the risk factors, the tumor phenotypes, and the BRCA1/BRCA2 genotype of early onset breast cancer (EOBC) patients between Southern Europe and North Africa. METHODS: Four hundred and fifty six women with invasive EOBC (≤40 years) were prospectively included from four centers in France (n = 270) and four centers in North Africa (Algeria, Egypt, Morocco, Tunisia; n = 186). Life style, tumor phenotype, familial history, BRCA1/BRCA2 genotype were compared between the two populations. RESULTS: We found an older age at menarche, a higher number of childbearing, a more frequent breastfeeding, a higher body mass index, a lower use of oral contraceptives in North African women compared to French women. TNM stage at diagnosis was higher in North African women than in French women. North African women had a lower incidence of triple negative and proliferative (Ki 67 index > 20%) tumors. There was a lower rate of BRCA1 mutation in North Africa (7 vs. 15%, P = 0.02). Three putative BRCA1/2 founder mutations were identified in North Africa. CONCLUSIONS: In EOBC, we found significant differences in risk factors, phenotype and a higher incidence of BRCA1 mutations in Southern Europe as compared to North Africa. The worst prognosis previously reported for EOBC in North Africa is more likely due to a higher stage at diagnosis than to a more aggressive phenotype, since triple negative tumors are more common in Southern Europe and advanced tumors in North Africa.

Prevention of multidrug-resistant infections from contaminated duodenoscopes: Position Statement of the European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Gastroenterology Nurses and Associates (ESGENA).

Patients should be informed about the benefits and risks of endoscopic retrograde cholangiopancreatography (ERCP)Only specially trained and competent personnel should carry out endoscope reprocessing.Manufacturers of duodenoscopes should provide detailed instructions on how to use and reprocess their equipment.In the case of modifications to their equipment, manufacturers should provide updated instructions for use.Detailed reprocessing protocols based on the manufacturer's instructions for use should clearly lay out the different reprocessing steps necessary for each endoscope model.Appropriate cleaning equipment should be used for duodenoscopes in compliance with the manufacturer's instructions for use. Only purpose-designed, endoscope type-specific, single-use cleaning brushes should be used, to ensure optimal cleaning. As soon as the endoscope is withdrawn from the patient, bedside cleaning should be performed, followed by leak testing, thorough manual cleaning steps, and automated reprocessing, in order to: · Remove debris from external and internal surfaces;. · Prevent any drying of body fluids, blood, or debris;. · Prevent any formation of biofilms.. In addition to the leak test, visual inspection of the distal end as well as regular maintenance of duodenoscopes should be performed according to the manufacturer's instructions for use, in order to detect any damage at an early stage.The entire reprocessing procedure in endoscope washer-disinfectors (EWDs) should be validated according to the European and International Standard, EN ISO 15883. Routine technical tests of EWDs should be performed according to the validation reports.Microbiological surveillance of a proportion of the department's endoscopes should be performed every 3 months, with the requirement that all endoscopes used in the unit are tested at least once a year.In the case of suspected endoscopy-related infection, the relevant device (e. g., endoscope, EWD) should be taken out of service until adequate corrective actions have been taken. Outbreaks should be managed by a multidisciplinary team, including endoscopy, hygiene, and microbiology experts, manufacturers, and regulatory bodies, according to national standards and/or laws. In the case of suspected multidrug-resistant organism (MDRO) outbreaks, close cooperation between the endoscopy unit and the clinical health provider is essential (including infection control departments and hospital hygienists).

ESGE-ESGENA technical specification for process validation and routine testing of endoscope reprocessing in washer-disinfectors according to EN ISO 15883, parts 1, 4, and ISO/TS 15883-5.

1 Prerequisites. The clinical service provider should obtain confirmation from the endoscope washer-disinfector (EWD) manufacturer that all endoscopes intended to be used can be reprocessed in the EWD. 2 Installation qualification. This can be performed by different parties but national guidelines should define who has the responsibilities, taking into account legal requirements. 3 Operational qualification. This should include parametric tests to verify that the EWD is working according to its specifications. 4 Performance qualification. Testing of cleaning performance, microbiological testing of routinely used endoscopes, and the quality of the final rinse water should be considered in all local guidelines. The extent of these tests depends on local requirements. According to the results of type testing performed during EWD development, other parameters can be tested if local regulatory authorities accept this. Chemical residues on endoscope surfaces should be searched for, if acceptable test methods are available. 5 Routine inspections. National guidelines should consider both technical and performance criteria. Individual risk analyses performed in the validation and requalification processes are helpful for defining appropriate test frequencies for routine inspections.

WEO position statement on hygiene in digestive endoscopy: Focus on endoscopy units in Asia and the Middle East.

The aim of this position statement is to reinforce the key points of hygiene in digestive endoscopy. The present article details the minimum hygiene requirements for reprocessing of endoscopes and endoscopic devices, regardless of the reprocessing method (automated washer-disinfector or manual cleaning) and the endoscopy setting (endoscopy suite, operating room, elective or emergency procedures). These minimum requirements are mandatory for patient safety. Both advanced diagnostic and therapeutic endoscopies should be carried out in an environment that is safe for patients and staff. Particular attention is given to contaminants. Procedural errors in decontamination, defective equipment, and failure to follow disinfection guidelines are major factors contributing to transmission of infection during endoscopy. Other important risk factors include inadequate cleaning, use of older endoscopes with surface and working channel irregularities, and contamination of water bottles or irrigating solutions. Infections by multidrug-resistant organisms have become an increasing problem in health-care systems worldwide. Since 2010, outbreaks of multidrug-resistant bacteria associated with endoscopic retrograde cholangiopancreatography have been reported from the USA, France, Germany, and The Netherlands. In many endoscopy units in Asia and the Middle East, reprocessing procedures have lagged behind those of Western countries for cultural reasons or lack of financial resources. This inconsistency in standards is now being addressed, and the World Endoscopy Organization has prepared this position statement to highlight key points for quality assurance in any endoscopy unit in any country.

Venous thromboembolism: What pharmacists know? What do they need?

INTRODUCTION: Venous thromboembolism is common in cancer. Low-molecular weight heparins are recommended for prolonged treatment (3-6 months or more if the cancer is active) and prevention of recurrence of venous thromboembolism in cancer. Community pharmacists are often faced with questions from patients. The main objective of this study was to describe the organization, practices and knowledge of pharmacists in care of venous thromboembolism in cancer patients. METHODS: A descriptive survey was conducted electronically in October and November 2013 with pharmacists in the Champagne-Ardenne region. The questionnaire collected data on the general organization of the pharmacy, management of outpatients with cancer and thrombosis, and the level of knowledge regarding recommendations on the management of thrombosis in patients with cancer. RESULTS: The participation rate was 31.6%. In 93% of cases, pharmacists had no particular expertise in oncology and/or supportive care. In addition, 96% did not know the existence of recommendations for "thrombosis in cancer." Finally, 49% gave the correct answer to the case report (low-molecular weight heparins). CONCLUSION: Training sessions on the management of venous thromboembolism in cancer are currently available to pharmacists in the region. A new assessment of knowledge will be performed at the end of the year 2014. This regional experience is now extended to a national level (all French regions).

Congenital hypogonadotropic hypogonadism with split hand/foot malformation: a clinical entity with a high frequency of FGFR1 mutations.

PURPOSE: Congenital hypogonadotropic hypogonadism (CHH) and split hand/foot malformation (SHFM) are two rare genetic conditions. Here we report a clinical entity comprising the two. METHODS: We identified patients with CHH and SHFM through international collaboration. Probands and available family members underwent phenotyping and screening for FGFR1 mutations. The impact of identified mutations was assessed by sequence- and structure-based predictions and/or functional assays. RESULTS: We identified eight probands with CHH with (n = 3; Kallmann syndrome) or without anosmia (n = 5) and SHFM, seven of whom (88%) harbor FGFR1 mutations. Of these seven, one individual is homozygous for p.V429E and six individuals are heterozygous for p.G348R, p.G485R, p.Q594*, p.E670A, p.V688L, or p.L712P. All mutations were predicted by in silico analysis to cause loss of function. Probands with FGFR1 mutations have severe gonadotropin-releasing hormone deficiency (absent puberty and/or cryptorchidism and/or micropenis). SHFM in both hands and feet was observed only in the patient with the homozygous p.V429E mutation; V429 maps to the fibroblast growth factor receptor substrate 2α binding domain of FGFR1, and functional studies of the p.V429E mutation demonstrated that it decreased recruitment and phosphorylation of fibroblast growth factor receptor substrate 2α to FGFR1, thereby resulting in reduced mitogen-activated protein kinase signaling. CONCLUSION: FGFR1 should be prioritized for genetic testing in patients with CHH and SHFM because the likelihood of a mutation increases from 10% in the general CHH population to 88% in these patients.