Updated European guidelines for clinical management of familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), gastric adenocarcinoma, proximal polyposis of the stomach (GAPPS) and other rare adenomatous polyposis syndromes: a joint EHTG-ESCP revision.

BACKGROUND: Hereditary adenomatous polyposis syndromes, including familial adenomatous polyposis and other rare adenomatous polyposis syndromes, increase the lifetime risk of colorectal and other cancers. METHODS: A team of 38 experts convened to update the 2008 European recommendations for the clinical management of patients with adenomatous polyposis syndromes. Additionally, other rare monogenic adenomatous polyposis syndromes were reviewed and added. Eighty-nine clinically relevant questions were answered after a systematic review of the existing literature with grading of the evidence according to Grading of Recommendations, Assessment, Development, and Evaluation methodology. Two levels of consensus were identified: consensus threshold (≥67% of voting guideline committee members voting either 'Strongly agree' or 'Agree' during the Delphi rounds) and high threshold (consensus ≥ 80%). RESULTS: One hundred and forty statements reached a high level of consensus concerning the management of hereditary adenomatous polyposis syndromes. CONCLUSION: These updated guidelines provide current, comprehensive, and evidence-based practical recommendations for the management of surveillance and treatment of familial adenomatous polyposis patients, encompassing additionally MUTYH-associated polyposis, gastric adenocarcinoma and proximal polyposis of the stomach and other recently identified polyposis syndromes based on pathogenic variants in other genes than APC or MUTYH. Due to the rarity of these diseases, patients should be managed at specialized centres.

Systematic Characterization of Defecographic Abnormalities in a Consecutive Series of 827 Patients With Chronic Constipation.

BACKGROUND: Barium defecography can assess structural and functional abnormalities in patients with chronic constipation. OBJECTIVE: The purpose of this study was to determine the prevalence of individual and overlapping defecographic findings in this setting. DESIGN: This was a cross-sectional study. SETTINGS: The study was conducted at a university hospital tertiary GI physiology department. PATIENTS: Consecutive examinations of 827 consecutive patients presenting over a 30-month period with well-defined symptom severity (≥12 points on the Cleveland Clinic Constipation score) were included. Systematic evaluation of images with results stratified by sex is described. MAIN OUTCOME MEASURES: Six individual functional or anatomic (intussusception, rectocele, enterocele, megarectum, excessive dynamic perineal descent) defecographic observations were defined a priori, thus permitting 26 possible combinations of findings (ie, 63 abnormal types + 1 normal). RESULTS: Patients with constipation (mean symptom score = 19) were predominantly female (88%), with median age of 49 years (range, 17-98 y) . All 6 individual radiologic findings were identified with a total of 43 combinations found in the cohort; the 14 most prevalent of these accounted for >85% of patients. Only 136 patients (16.4%) had a normal defecography (34.3% males vs 13.9% females; p < 0.0001). Overall, 612 patients (74.0%) had structural (n = 508 (61.4%)) or functional (n=104 (12.6%)) abnormalities in isolation, with 79 (9.6%) others exhibiting combinations of both. Functional abnormalities in isolation were more common in males compared with females (22.5% vs11.2%; p = 0.025) as opposed to structural abnormalities (57.8% vs 85.7%; p < 0.0001). Expulsion time was longer in females compared with males (110 s (60-120 s) vs 90 s (60-120 s); p = 0.049). LIMITATIONS: The study was limited by its lack of multiorgan opacification. CONCLUSIONS: These results provide a contemporary atlas of defecographic findings in constipation. Several individual structural and functional features have been systematically classified, with overlap greater than previously acknowledged and profound differences among sexes that carry implications for tailoring management. See Video Abstract at http://links.lww.com/DCR/B552. CARACTERIZACIN SISTEMTICA DE ANOMALAS DEFECOGRFICAS EN UNA SERIE CONSECUTIVA DE PACIENTES CON ESTREIMIENTO CRNICO: ANTECEDENTES:La defecografía con bario puede evaluar anomalías estructurales y funcionales en pacientes con estreñimiento crónico.OBJETIVO:Determinar la prevalencia de hallazgos defecográficos individuales y superpuestos en este entorno.DISEÑO:Transversal.ENTORNO CLINICO:Hospital Universitario de tercer nivel, departamento de fisiología gastrointestinal.PACIENTES:Exploraciones consecutivas de 827 pacientes consecutivos que se presentaron durante un período de 30 meses con una gravedad de los síntomas bien definida (≥12 puntos en la escala de estreñimiento de la Cleveland Clinic): evaluación sistemática de imágenes con resultados estratificados por sexo.PRINCIPALES MEDIDAS DE VALORACION:Se definieron a priori seis observaciones defecográficas individuales, funcionales o anatómicas (intususcepción, rectocele, enterocele, megarecto, descenso perineal dinámico excesivo), lo que permitió 26 combinaciones posibles de hallazgos (es decir, 63 tipos anormales + 1 normal).RESULTADOS:Los pacientes con estreñimiento (puntuación media de síntomas, 19) eran predominantemente mujeres (88%) con una edad mediana de 49 (17-98) años. Se identificaron 6 hallazgos radiológicos individuales con un total de 43 combinaciones encontradas en la cohorte; los 14 más predominantes de éstos representaron >85% de los pacientes.Solo 136 (16,4%) pacientes tuvieron una defecografía normal (34,3% hombres vs. 13,9% mujeres; P < 0,0001). En general, 612 (74,0%) pacientes tenían anomalías estructurales (n = 508 [61,4%]) o funcionales (n = 104 [12,6%]) de forma aislada, y otros 79 (9,6%) presentaban combinaciones de ambas. Las anomalías funcionales aisladas fueron más comunes en los hombres en comparación con las mujeres (22,5% vs. 11,2%, P = 0,025) en comparación con las anomalías estructurales (57,8 vs. 85,7%, P < 0,0001). El tiempo de expulsión fue mayor en las mujeres en comparación con los hombres (110 [60-120] vs. 90 [60-120] segundos; P = 0,049).LIMITACIONES:Falta de opacificación multiorgánica.CONCLUSIONES:Estos resultados proporcionan un atlas contemporáneo de hallazgos defecográficos en estreñimiento. Varias características individuales, estructurales y funcionales; se han clasificado sistemáticamente, con una superposición mayor que la reconocida anteriormente y con grandes diferencias entre los sexos que tienen implicaciones para adaptar su tratamiento. Consulte Video Resumen en http://links.lww.com/DCR/B552.

Abdominal pain in patients with inflammatory bowel disease: association with single-nucleotide polymorphisms prevalent in irritable bowel syndrome and clinical management.

BACKGROUND: Abdominal pain is a frequent symptom in patients with inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC). Pain can result from ongoing inflammation or functional disorders imitating irritable bowel syndrome (IBS). Several single-nucleotide polymorphisms (SNPs) have been associated with IBS. However, the impact of IBS genetics on the clinical course of IBD, especially pain levels of patients remains unclear. METHODS: Data of 857 UC and 1206 CD patients from the Swiss IBD Cohort Study were analysed. We tested the association of the maximum of the abdominal pain item of disease activity indices in UC and CD over the study period with 16 IBS-associated SNPs, using multivariate ANOVA models. RESULTS: In UC patients, the SNPs rs1042713 (located on the ADRB2 gene) and rs4663866 (close to the HES6 gene) were associated with higher abdominal pain levels (P = 0.044; P = 0.037, respectively). Abdominal pain was not associated with any markers of patient management in a model adjusted for confounders. In CD patients, higher levels of abdominal pain correlated with the number of physician contacts (P < 10-15), examinations (P < 10-12), medical therapies (P = 0.023) and weeks of hospitalisation (P = 0.0013) in a multivariate model. CONCLUSIONS: We detected an association between maximal abdominal pain in UC patients and two IBS-associated SNPs. Abdominal pain levels had a pronounced impact on diagnostic and therapeutic procedures in CD but not in UC patients.

Improved treatment outcome and lower skin toxicity with intensity-modulated radiotherapy vs. 3D conventional radiotherapy in anal cancer.

PURPOSE: Radiochemotherapy is the standard treatment for anal carcinoma (ACa). Intensity-modulated radiotherapy (IMRT) has been introduced, allowing focused irradiation of the tumor area. Whether physical benefits of IMRT translate to clinical benefits has not been sufficiently demonstrated. METHODS: We retrospectively reviewed data from 82 patients with newly diagnosed ACa. Patients treated with IMRT were compared with previous patients treated with conventional three-dimensional computational radiotherapy (3D-CRT). The influence of IMRT on complete remission and acute and chronic side effects was analyzed in univariate and multivariate analyses. RESULTS: 39/40 patients treated with IMRT were in complete remission after 1 year compared to 31/39 patients treated with 3D-CRT (p = 0.014). Multivariate analysis confirmed tumor T stage as well as lack of IMRT treatment as risk factors for persistent tumor at 6 months. No significant benefits of IMRT were apparent at later timepoints (median follow up 52 months, IQR: 31.5-71.8 months). Patients treated with IMRT had a significantly lower degree of skin toxicity (median 2 vs. 3 in a scale ranging from 0 to 3, p = 0.00092). Rates of hematological toxicity/proctitis were not reduced and rates of acute diarrhea increased (p = 0.034). Median length of hospitalization tended to be shorter in patients treated with IMRT (n. s.). CONCLUSION: We present a real-world experience of shifting radiation technique from conventional 3D-CRT to IMRT. IMRT patients had better tumor control at 1 year and lower degrees of skin toxicity. Our data indicate that IMRT can enable therapies with lower side effects with equal or better oncological results for patients with ACa.

Effect of cocoa on the brain and gut in healthy subjects: a randomised controlled trial.

Dark chocolate is claimed to have effects on gastrointestinal function and to improve well-being. This randomised controlled study tested the hypothesis that cocoa slows gastric emptying and intestinal transit. Functional brain imaging identified central effects of cocoa on cortical activity. Healthy volunteers (HV) ingested 100 g dark (72 % cocoa) or white (0 % cocoa) chocolate for 5 d, in randomised order. Participants recorded abdominal symptoms and stool consistency by the Bristol Stool Score (BSS). Gastric emptying (GE) and intestinal and colonic transit time were assessed by scintigraphy and marker studies, respectively. Combined positron emission tomography-computed tomography (PET-CT) imaging assessed regional brain activity. A total of sixteen HV (seven females and nine males) completed the studies (mean age 34 (21-58) years, BMI 22·8 (18·5-26·0) kg/m2). Dark chocolate had no effect on upper gastrointestinal function (GE half-time 82 (75-120) v. 83 (60-120) min; P=0·937); however, stool consistency was increased (BSS 3 (3-5) v. 4 (4-6); P=0·011) and there was a trend to slower colonic transit (17 (13-26) v. 21 (15-47) h; P=0·075). PET-CT imaging showed increased [18F]fluorodeoxyglucose (FDG) in the visual cortex, with increased FDG uptake also in somatosensory, motor and pre-frontal cortices (P<0·001). In conclusion, dark chocolate with a high cocoa content has effects on colonic and cerebral function in HV. Future research will assess its effects in patients with functional gastrointestinal diseases with disturbed bowel function and psychological complaints.

Surveillance of anal carcinoma after radiochemotherapy : A retrospective analysis of 80 patients.

BACKGROUND: Surveillance after radiochemotherapy of anal carcinoma (ACa) with curative intent is recommended in guidelines, but data regarding the effectiveness of follow-up are lacking. We aimed to assess the performance of an ACa surveillance program in a real-life setting. METHODS: We retrospectively summarized clinical history, physical findings, and follow-up investigations (endoanal ultrasound, endoscopy, CT scan) obtained during 42 months (±27 months) from 80 patients after radiochemotherapy of ACa. RESULTS: In 7/80 cases (8.8%) an incomplete response to therapy was identified at or before the 6­month time point after the end of treatment; 4 of the 7 cases were identified during scheduled follow-up. In 6 cases (7.5%), recurrent disease was found after the 6­month time point. Recurrence was systemic in 5 cases and local/inguinal in 1 case. In 3 of the 6 cases (50%), recurrence was identified during scheduled follow-up. In one asymptomatic patient, a single liver metastasis was detected during scheduled follow-up and the patient remains free of disease 19 months after surgery. Surveillance resulted in a high rate of false-positive findings (70 findings in 604 investigations), of which only 14 could be confirmed. CONCLUSION: Scheduled follow-up after treatment of ACa detected recurrent disease at systemic sites, enabling potentially curative treatment in a single case. Effectiveness of abdominal imaging during follow-up after ACa treatment should be tested in a prospective trial.

CMOST: an open-source framework for the microsimulation of colorectal cancer screening strategies.

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer-related mortality. CRC incidence and mortality can be reduced by several screening strategies, including colonoscopy, but randomized CRC prevention trials face significant obstacles such as the need for large study populations with long follow-up. Therefore, CRC screening strategies will likely be designed and optimized based on computer simulations. Several computational microsimulation tools have been reported for estimating efficiency and cost-effectiveness of CRC prevention. However, none of these tools is publicly available. There is a need for an open source framework to answer practical questions including testing of new screening interventions and adapting findings to local conditions. METHODS: We developed and implemented a new microsimulation model, Colon Modeling Open Source Tool (CMOST), for modeling the natural history of CRC, simulating the effects of CRC screening interventions, and calculating the resulting costs. CMOST facilitates automated parameter calibration against epidemiological adenoma prevalence and CRC incidence data. RESULTS: Predictions of CMOST were highly similar compared to a large endoscopic CRC prevention study as well as predictions of existing microsimulation models. We applied CMOST to calculate the optimal timing of a screening colonoscopy. CRC incidence and mortality are reduced most efficiently by a colonoscopy between the ages of 56 and 59; while discounted life years gained (LYG) is maximal at 49-50 years. With a dwell time of 13 years, the most cost-effective screening is at 59 years, at $17,211 discounted USD per LYG. While cost-efficiency varied according to dwell time it did not influence the optimal time point of screening interventions within the tested range. CONCLUSIONS: Predictions of CMOST are highly similar compared to a randomized CRC prevention trial as well as those of other microsimulation tools. This open source tool will enable health-economics analyses in for various countries, health-care scenarios and CRC prevention strategies. CMOST is freely available under the GNU General Public License at https://gitlab.com/misselwb/CMOST.

Assessment of Obstructive Defecation by High-Resolution Anorectal Manometry Compared With Magnetic Resonance Defecography.

BACKGROUND & AIMS: Patients with obstructive defecation have abnormalities of anorectal function and/or structure. Conventional anorectal manometry (ARM) can identify abnormal function and behavior (dyssynergia); however, agreement between manometry and defecography is only fair. High-resolution (HR)-ARM may improve diagnostic agreement by differentiating pressure effects caused by dyssynergia and obstruction. We compared HR-ARM findings with magnetic resonance (MR) defecography in the clinical assessment of patients with symptoms of obstructive defecation defined by Rome III criteria. METHODS: HR-ARM (Manoscan AR 360; Given Imaging, Yoqeam, Israel) assessed anal sphincter function and pressure during simulated defecation. Abnormal manometric findings were classified according to the Rao system and compared with MR defecography as the reference standard. RESULTS: A total of 188 consecutive patients (155 women; age, 19-93 y) with obstructive defecation underwent a full investigation. Compared with patients with dyssynergia on MR imaging (n = 66), patients with structural pathology (n = 87) had lower resting (P < .003) and squeeze pressures (P < .011), but a higher rectoanal pressure gradient (P < .0001) on HR-ARM. High intrarectal pressure with a steep, positive pressure gradient consistent with outlet obstruction on HR-ARM was present in 24 patients with intra-anal intussusception on MR imaging. This pattern was not observed in other patients. Interobserver agreement was substantial for HR-ARM diagnoses (κ = 0.67; 95% confidence interval, 0.559-0.779). Diagnostic accuracy for dyssynergia was 82% compared with MR imaging (sensitivity, 77% [51 of 66]; specificity, 85% [104 of 122]). CONCLUSIONS: The diagnostic agreement between anorectal HR-ARM and MR defecography is high and pressure measurements accurately identify recto-anal dyssynergia and intra-anal outlet obstruction by structural pathology as causes of obstructive defecation.

Peroral endoscopic myotomy for the treatment of achalasia: an international prospective multicenter study.

Pilot studies have indicated that peroral endoscopic myotomy (POEM) might be a safe and effective treatment for achalasia. We performed a prospective, international, multicenter study to determine the outcomes of 70 patients who underwent POEM at 5 centers in Europe and North America. Three months after POEM, 97% of patients were in symptom remission (95% confidence interval, 89%-99%); symptom scores were reduced from 7 to 1 (P < .001) and lower esophageal sphincter pressures were reduced from 28 to 9 mm Hg (P < .001). The percentage of patients in symptom remission at 6 and 12 months was 89% and 82%, respectively. POEM was found to be an effective treatment for achalasia after a mean follow-up period of 10 months.

[Bloody diarrhoea - causes, diagnostics and therapy]. / Blutige Diarrhoe - Ätiologie, Diagnostik und Therapie.

Bloody diarrhoea is always a warning sign and should prompt a more thorough history on duration and accompanying symptoms as well as current medications (antibiotics, NSAR) and diseases (HIV, IBD, transplant organ recipients). In this review the most common bacterial, viral and parasitical causes of bloody diarrhoea as well as radiation and ischemic colitis will be discussed. Additionally important diagnostic tools such as stool cultures and calprotectin for infectious causes auf diarrhoea and imaging tools (CT and endoscopy) for ischemic disease are presented. The causes of bloody diarroea in immunosuppressed patients and IBD are additionally addressed.

The Pierced Colon: When Biliary Stents Go the Wrong Way.

Bowel perforation of biliary stents is a rare complication of biliary stenting. We report the successful endoscopic treatment of a 78-year-old man with a straight biliary plastic stent perforating the ascending colon without underlying structural abnormality in the affected segment. Perforation was detected incidentally during computed tomography; the patient had been under continued antibiotic therapy for liver abscess. Stent extraction was performed by using an endoscopic snare; the site of perforation was closed with through-the-scope clips. The patient remained asymptomatic. In addition, we reviewed published cases of perforated biliary stents and outlined that most perforations are caused by straight plastic stents.

[Frequent Gastro-Intestinal Disorders: Management of Functional Dyspepsia and Irritable Bowel Syndrome in Clinical Practice]. / Häufige Magen-Darm-Beschwerden: Management der funktionellen Dyspepsie und des Reizdarm-Syndroms in der Praxis.

Frequent Gastro-Intestinal Disorders: Management of Functional Dyspepsia and Irritable Bowel Syndrome in Clinical Practice Abstract: Functional dyspepsia (FD) and irritable bowel syndrome (IBS), two common gastrointestinal entities with overlapping symptoms, should be diagnosed according to Rome IV criteria. This includes one or more of the following symptoms: in FD, postprandial fullness, early satiation, epigastric pain or burning; in IBS, recurrent abdominal pain associated with defecation, change in frequency of stool or form of stool. To exclude structural diseases, attention should be paid to alarm symptoms. As far as treatment is concerned, a stepwise scheme proves to be effective for both diseases. Step 1: doctor-patient discussion with explanation of diagnosis and prognosis as well as clarification of therapy goals; lifestyle adaptations; use of phytotherapeutics; step 2: symptom-oriented medication: for FD, PPIs or prokinetics; for IBS, antispasmodics, secretagogues, laxatives, bile acid sequestrants, antidiarrheals, antibiotics, probiotics; step 3: visceral analgesics (antidepressants).

Impact of Vedolizumab on Extraintestinal Manifestations in Inflammatory Bowel Disease: Results From a Descriptive, Retrospective, Real-world Study.

BACKGROUND: Patients with inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, may develop extraintestinal manifestations (EIMs). The EMOTIVE study aimed to analyze the effect of vedolizumab on EIMs in a real-world cohort of patients with IBD. METHODS: This multicenter, descriptive, retrospective study was conducted in Belgium, Denmark, Israel, the Netherlands, and Switzerland in adults with moderately to severely active IBD and concurrent active EIMs at vedolizumab initiation (index date), with a ≥6-month follow-up after the index date. The primary endpoint was resolution of all EIMs within 6 months of vedolizumab initiation. RESULTS: In 99 eligible patients, the most frequent EIMs were arthralgia (69.7%), peripheral spondyloarthritis (21.2%), and axial spondyloarthritis (10.1%). Within 6 and 12 months of vedolizumab initiation, 19.2% and 25.3% of patients reported resolution of all EIMs, while 36.5% and 49.5% of all EIMs were reported to be improved (combination of resolution and partial response), respectively. Vedolizumab treatment persistence at 12 months was 82.8%. Adverse events were reported in 18.2% of patients, with the most frequent being arthralgia (4.0%). CONCLUSIONS: This real-world study showed resolution of all EIMs in up to one-fourth of patients with IBD and improvement in up to half of EIMs within 12 months of vedolizumab treatment. Overall, vedolizumab was effective on EIMs in patients with IBD and showed a good safety profile.

Increased prevalence of gastrointestinal symptoms and disorders of gut-brain interaction during the COVID-19 pandemic: An internet-based survey.

BACKGROUND: Quarantine with social distancing has reduced transmission of COVID-19; however, fear of the disease and these remedial measures cause anxiety and stress. It is not known whether these events have impacted the prevalence of gastrointestinal (GI) symptoms and disorders of brain-gut interaction (DGBI). METHODS: An online platform evaluated the prevalence of GI symptoms during the COVID-19 pandemic. Data collection utilized validated questionnaires and was fully anonymized. Findings were compared with identical data acquired in 2019. The association of results with stress and anxiety was analyzed. RESULTS: Data were collected from 1896 subjects May - August 2019 to 980 non-identical subjects May - June 2020. GI symptoms were reported by 68.9% during the COVID-19 lockdown compared with 56.0% the previous year (p < 0.001). The prevalence of irritable bowel syndrome (26.3% vs. 20.0%; p < 0.001), functional dyspepsia (18.3% vs. 12.7%; p < 0.001), heartburn (31.7% vs. 26.2%, p = 0.002), and self-reported milk intolerance (43.5% vs. 37.8% p = 0.004) was higher during the pandemic. Many individuals reported multiple symptoms. Anxiety was associated with presence of all GI symptoms. High levels of stress impacted functional dyspepsia (p = 0.045) and abdominal pain (p = 0.013). The presence of DGBI (p < 0.001; OR 22.99), self-reported milk intolerance (p < 0.001; OR 2.50), and anxiety (p < 0.001; OR 2.18) was independently associated with increased GI symptoms during COVID-19 pandemic. CONCLUSIONS: The prevalence of GI symptoms was significantly higher during the COVID-19 lockdown than under normal circumstances the previous year. This increase was attributable to increased numbers of patients with DGBI, an effect that was associated with anxiety.

The present and future of gastroenterology and hepatology: an international SWOT analysis (the GASTROSWOT project).

GASTROSWOT is a strategic analysis of the current and projected states of the different subspecialties in gastroenterology that aims to provide guidance for research, clinical, and financial planning in gastroenterology. We executed a consensus-based international strengths, weaknesses, opportunities, and threats (SWOT) analysis. Four general coordinators, six field coordinators, and 12 experts participated in the study. SWOTs were provided for the following fields: neurogastroenterology, functional gastrointestinal disorders, and upper gastrointestinal diseases; inflammatory bowel disease; pancreatology and biliary diseases; endoscopy; gastrointestinal oncology; and hepatology. The GASTROSWOT analysis highlights the following in the current state of the field of gastroenterology: the incidence and complexity of several gastrointestinal diseases, including malignancies, are increasing; the COVID-19 pandemic has affected patient care on several levels; and with the advent of technical innovations in gastroenterology, a well trained workforce and strategic planning are required to optimise health-care utilisation. The analysis calls attention to the following in the future of gastroenterology: artificial intelligence and the use of big data will speed up discovery and smarter health-care provision in the field; the growth and diversification of gastroenterological specialties will improve specialised care for patients, but could promote fragmentation of care and health system inefficiencies; and furthermore, thoughtful planning is needed to reach an effective balance between the need for subspecialists and the value of general gastroenterology services.

Young GI angle: Living through a crisis: How to manage downturns in your career.

Depending on its reason, a crisis can last a time and needs patience and persistence to be solved. First, you feel the shot and realize what is happening. Then, you will probably remain shocked for some time, and you will need time to manage the crisis and get back on your feet. Moreover, you must consider, that after the end of the acute crisis, that a recovery period will be necessary to adapt yourself to the new environment and stand up again. During that time frame, it could be extremely hard to go ahead with your clinical and scientific career (e.g., learning new skills or carrying on new research), and you can feel scared. Because we humans are programmed to be skeptical when it comes to change-although it is an eternal constant. Also do not be afraid of wasting or losing time: even if it will take months to solve the issue, this time will not be wasted. You will have found a new balance, and, more importantly, you will have learned important skills how to manage a difficult situation and be ready for the next one. The term "crisis" means originally "separation". This can reflect both the need of a choice and the fact that, after a crisis, you will not be the same. Despite being unpleasant, a crisis can be an opportunity for your life and your career-it can make you understand what you really want, depending on your ideas and your ambitions. A re-establishment of your environment can be fruitful for your career and your motivation-so do not hesitate to embrace change and learn from it.

Recommendations for the diagnosis and management of transthyretin amyloidosis with gastrointestinal manifestations.

Transthyretin amyloid (ATTR) amyloidosis is an adult-onset, rare systemic disorder characterized by the accumulation of misfolded fibrils in the body, including the peripheral nerves, the heart and the gastrointestinal tract. Gastrointestinal manifestations are common in hereditary (ATTRv) amyloidosis and are present even before the onset of the polyneuropathy in some cases. Delays in diagnosis of ATTRv amyloidosis with gastrointestinal manifestations commonly occur because of fragmented knowledge among gastroenterologists and general practitioners, as well as a shortage of centers of excellence and specialists dedicated to disease management. Although the disease is becoming well-recognized in the societies of Neurology and Cardiology, it is still unknown for most gastroenterologists. This review presents the recommendations for ATTRv amyloidosis with gastrointestinal manifestations elaborated by a working group of European gastroenterologists and neurologists, and aims to provide digestive health specialists with an overview of crucial aspects of ATTRv amyloidosis diagnosis to help facilitate rapid and accurate identification of the disease by focusing on disease presentation, misdiagnosis and management of gastrointestinal symptoms.

Data linkage to evaluate the long-term risk of HIV infection in individuals seeking post-exposure prophylaxis.

Evidence on the long-term risk of HIV infection in individuals taking HIV post-exposure prophylaxis remains limited. In this retrospective data linkage study, we evaluate the occurrence of HIV infection in 975 individuals who sought post-exposure prophylaxis in a tertiary hospital between 2007 and 2013. Using privacy preserving probabilistic linkage, we link these 975 records with two observational databases providing data on HIV events (Zurich Primary HIV Infection study and the Swiss HIV Cohort Study). This enables us to identify 22 HIV infections and to obtain long-term follow-up data, which reveal a median of 4.1 years between consultation for post-exposure prophylaxis and HIV diagnosis. Even though men who have sex with men constitute only 35.8% of those seeking post-exposure prophylaxis, all 22 events occur in this subgroup. These findings should strongly encourage early consideration of pre-exposure prophylaxis in men who have sex with men after a first episode of post-exposure prophylaxis.

Endoscopic mucosal resection for staging and therapy of adenocarcinoma of the esophagus, gastric cardia, and upper gastric third.

Minamally invasive endoscopic resection techniques allow definitive histological staging for dysplasia and early cancer and in many cases curative treatment. In Barrett's esophagus with High Grade Dysplasia (HGD) or early mucosal cancer, endoscopic mucosal resection (EMR) should be considered both as diagnostic and therapeutic first line procedure, with the possibility to repeat the procedure in case of residual Barrett's dysplasia or mucosal cancer. In early cancer of the the submucosa, surgical resection should be discussed. Endoscopic submucosal dissection (ESD) is a useful therapeutic option for HGD or early cancer in the squamous epithelium of the esophagus or in the stomach when en bloc resection is needed in large lesions.