Joana Moleiro

Impact of Early Surgery and Immunosuppression on Crohnʼs Disease Disabling Outcomes

Background and Aims: The definition of early therapeutic strategies to control Crohns disease aggressiveness and prevent recurrence is key to improve clinical practice. This study explores the impact of early surgery and immunosuppression onset in the occurrence of disabling outcomes. Methods: This was a multicentric and retrospective study with 754 patients with Crohns disease, who were stratified according to the need for an early surgery (group S) or not (group I) and further divided according to the time elapsed from the beginning of the follow-up to the start of immunosuppression therapy. Results: The rate of disabling events was similar in both groups (S: 77% versus I: 76%, P = 0.700). The percentage of patients who needed surgery after or during immunosuppression therapy was higher among group S, both for first surgeries after the index event (38% of groups S versus 21% of group I, P < 0.001) and for reoperations (38% of groups S versus 12% of group I, P < 0.001). The time elapsed to reoperation was shorter in group I (HR = 2.340 [1.367–4.005]), stratified for the onset of immunosuppression. Moreover, reoperation was far more common among patients who had a late start of immunosuppression (S36: 50% versus S0–6: 27% and S6–36: 25%, P < 0.001) and (I36: 16% versus I0–6: 5% and I6–36: 7%, P < 0.001). Conclusions: Although neither early surgery nor immunosuppression seem to be able to prevent global disabling disease, an early start of immunosuppression by itself is associated with fewer surgeries and should be considered in daily practice as a preventive strategy.

Accuracy of Faecal Calprotectin and Neutrophil Gelatinase B-associated Lipocalin in Evaluating Subclinical Inflammation in UlceRaTIVE Colitis-the ACERTIVE study.

Background and Aims Mucosal healing and histological remission are different targets for patients with ulcerative colitis, but both rely on an invasive endoscopic procedure. This study aimed to assess faecal calprotectin and neutrophil gelatinase B-associated lipocalin as biomarkers for disease activity in asymptomatic ulcerative colitis patients. Methods This was a multicentric cross-sectional study including 371 patients, who were classified according to their endoscopic and histological scores. These results were evaluated alongside the faecal levels of both biomarkers. Results Macroscopic lesions [i.e. endoscopic Mayo score ≥1] were present in 28% of the patients, and 9% had active disease according to fht Ulcerative Colitis Endoscopic Index of Severity. Moreover, 21% presented with histological inflammation according to the Geboes index, whereas 15% and 5% presented with focal and diffuse basal plasmacytosis, respectively. The faecal levels of calprotectin and neutrophil gelatinase B-associated lipocalin were statistically higher for patients with endoscopic lesions and histological activity. A receiver operating characteristic-based analysis revealed that both biomarkers were able to indicate mucosal healing and histological remission with an acceptable probability, and cut-off levels of 150-250 μg/g for faecal calprotectin and 12 μg/g for neutrophil gelatinase B-associated lipocalin were proposed. Conclusions Faecal calprotectin and neutrophil gelatinase B-associated lipocalin levels are a valuable addition for assessment of disease activity in asymptomatic ulcerative colitis patients. Biological levels of the analysed biomarkers below the proposed thresholds can rule out the presence of macroscopic and microscopic lesions with a probability of 75-93%. However, caution should be applied whenever interpreting positive results, as these biomarkers present consistently low positive predictive values.

Gastric malt lymphoma: Analysis of a series of consecutive patients over 20 years

Introduction and aims Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is closely associated with Helicobacter pylori (HP) infection. Our aim was to evaluate demographic, clinical and endoscopic characteristics of gastric MALT lymphoma patients, as well as to analyse response to treatment and factors that affect complete remission (CR) and relapse. We also assessed the long-term prognosis. Methods The study involved a retrospective evaluation of consecutive patients admitted with gastric MALT lymphoma (1993–2013). Results A total of 144 patients (76 men; mean age 56) were included. At stage EI, 94/103 patients (92%) received HP eradication and 78 (83%) achieved CR after a mean period of 7 months (2–63 months) and 67 (86%) remained in CR after a mean follow-up time of 105 months. HP infection status (p = 0.004) and lymphoma localisation to the antrum plus body (p = 0.016) were associated with higher and lower CR rates, respectively. Relapse occurred in 11/78 (14%) patients after a mean period of 21 months. The absence of HP re-infection (p = 0.038), the need of only one eradication regimen (p = 0.009) and antrum lymphomas (p = 0.031) correlated with lower relapse rates. At stage EII, HP eradication was performed in 17/24 patients but only five experienced CR (30%). Among 16 patients diagnosed at stage EIV, nine achieved CR after chemotherapy ± surgery and 3/7 without remission died due to disease progression. The 5- and 10-year overall disease free survival rates were 90.5% and 79.1%, respectively. Conclusions Most patients were diagnosed at an early stage. Eradication therapy was highly effective in inducing complete remission. Long-term evaluation showed that the long-term prognosis was very favourable.

Comparison of different histological indexes in the assessment of UC activity and their accuracy regarding endoscopic outcomes and faecal calprotectin levels

Objective Histological remission is being increasingly acknowledged as a therapeutic endpoint in patients with UC. The work hereafter described aimed to evaluate the concordance between three histological classification systems—Geboes Score (GS), Nancy Index (NI) and RobartsHistopathologyIndex (RHI), as well as to evaluate their association with the endoscopic outcomes and the faecal calprotectin (FC) levels. Design Biopsy samples from 377 patients with UC were blindly evaluated using GS, NI and RHI. The results were compared with the patients’ Mayo Endoscopic Score and FC levels. Result GS, NI and RHI have a good concordance concerning the distinction between patients in histological remission or activity. RHI was particularly close to NI, with 100% of all patients classified as being in remission with NI being identified as such with RHI and 100% of all patients classified as having activity with RHI being identified as such with NI. These scores could also predict the Mayo Endoscopic Score and the FC levels, with their sensitivity and specificity levels depending on the chosen cut-offs. Moreover, higher FC levels were statistically associated with the presence of neutrophils in the epithelium, as well as with ulceration or erosion of the intestinal mucosa. Conclusions GS, NI and RHI histopathological scoring systems are comparable in what concerns patients’ stratification into histological remission/activity. Additionally, FC levels are increased when neutrophils are present in the epithelium and the intestinal mucosa has erosions or ulcers. The presence of neutrophils in the epithelium is, indeed, the main marker of histological activity.

Efficacy of Long-Term Oral Vitamin B12 Supplementation after Total Gastrectomy: Results from a Prospective Study.

Background/Objectives: Vitamin B12 (VB12) deficiency is a common complication after total gastrectomy which may be associated with megaloblastic anemia and potentially irreversible neurologic symptoms. Intramuscular supplementation of VB12 has been considered the standard treatment, although it is associated with high costs and patient discomfort. Patients/Methods: We performed a prospective uncontrolled study (ACTRN12614000107628) in order to evaluate the clinical and laboratory efficacy of long-term oral VB12 supplementation in patients submitted to total gastrectomy. All patients received daily oral VB12 (1 mg/day) and were evaluated every 3 months (clinical and laboratory evaluation: hemoglobin, VB12, total iron, ferritin, and folate). Results: A total of 26 patients were included with a mean age of 64 years (29-79). Patients were included with a mean period of 65 months (3-309) after total gastrectomy. At inclusion time, 17/26 patients were under intramuscular VB12, and 9 had not started supplementation yet. There were normal serum VB12 levels in 25/26 patients (mean VB12 serum levels: 657 pg/mL). The mean follow-up period was 20 (8.5-28) months. During follow-up, all patients had normal VB12 levels and there was no need for intramuscular supplementation. The patient with low VB12 levels had an increase to adequate levels, which remained stable. There were no differences with statistical significance among VB12 levels at 6 (867 pg/mL), 12 (1,008 pg/mL), 18 (1,018 pg/mL), and 24 (1,061 pg/mL) months. Iron and folate supplementation was necessary in 21 and 7 patients, respectively. Conclusions: Oral VB12 supplementation is effective and safe in patients who underwent total gastrectomy and should be considered the preferential form of supplementation.

Calprotectin and the Magnitude of Antibodies to Infliximab in Clinically-stable Ulcerative Colitis Patients are More Relevant Than Infliximab Trough Levels and Pharmacokinetics for Therapeutic Escalation

Although infliximab (IFX) is an efficient therapy for ulcerative colitis (UC) patients, a considerably high rate of therapeutic failures still occurs. This study aimed at a better understanding of IFX pharmacokinetics and pharmacodynamics among clinically-asymptomatic UC patients. This was a multicentric and prospective study involving 65 UC patients in the maintenance phase of IFX therapy. There were no significant differences between patients with positive and negative clinical, endoscopic and histological outcomes concerning their IFX trough levels (TLs), area under the IFX concentration vs. time curve (AUC), clearance and antibodies to infliximab (ATI) levels. However, the need to undergo therapeutic escalation later in disease development was significantly associated with higher ATI levels (2.62 μg/mL vs. 1.15 μg/mL, p = 0.028). Moreover, and after adjusting for disease severity, the HR (hazard ratio) for therapeutic escalation was significantly decreased for patients with an ATI concentration below 3 μg/mL (HR = 0.119, p = 0.010), and increased for patients with fecal calprotectin (FC) level above 250 μg/g (HR = 9.309, p = 0.018). In clinically-stable UC patients, IFX pharmacokinetic features cannot predict therapeutic response on a short-term basis. However, high levels of ATIs or FC may be indicative of a future therapeutic escalation.

UEG Visiting Fellowship Programme – my experience with the Visiting Fellowship for Clinicians Award

The United European Gastroenterology (UEG) Visiting Fellowship Programme is an UEG award whose aim is to increase the interaction between young clinicians and prestigious European training centres and to create new windows of clinical and scientific collaboration. In this programme, selected fellows are invited to visit the centre for a two-week period, prolongation being strongly encouraged. Since my first fruitful experience with an UEG education course – Young Investigators Meeting 2014 in Vienna – I have been always connected with UEG courses, programmes and activities. In fact, UEG allows me, as a trainee, to progress in gastroenterology care. And it was due to this permanent contact that I learnt about UEG awards, particularly, UEG Visiting Fellowship for Clinicians. I quickly realised that I could not miss the opportunity to broaden my networking and educational experience in pursuit of a more wellrounded gastrointestinal and scientific education. And as one of the first five selected participants I couldn’t be more grateful and happy! In June 2016 I had the wonderful opportunity to make a visit as clinical observer in the Department of Gastroenterology and Hepatology in the Radboud University Medical Center, Nijmegen, The Netherlands. Professor Joost Drenth and Professor Peter Siersema were my hosts. The Department of Gastroenterology and Hepatology is a reference centre, distinguished in gastroenterology, particularly in the area of liver (mainly polycystic liver disease) and pancreatic diseases, which deals with a large volume of cases and has performed intense scientific work in these fields. Furthermore, the largest population of Dutch patients receiving parenteral nutrition is under treatment in the department, providing me with a better knowledge of the indications for parental nutrition in order to be able to implement nutritional therapies and face the associated complications. I had the chance to make contact with brilliant doctors and skilled scientists, in a department where team work was very stimulating. During my stay, in order to benefit as much as possible from this experience, I divided my time between Morning reports and Endoscopy at the Endoscopy Center, liver disease patients’ consultation, ward rounds at the nursing department and teaching sessions. In liver consultation I worked with Professor Drenth, who has enormous experience in the field of liver diseases. I had contact with patients with rare liver diseases which gave me the opportunity to develop my knowledge and skills in the diagnostics and therapeutics of liver diseases. In the ward rounds I contacted mostly patients with pancreatic diseases, complications of parenteral nutrition and short bowel syndrome. In the Endoscopy Center I had the chance to observe the routine of the area, as well as advanced procedures in endoscopy. During those weeks, I also had the opportunity to attend some scientific meetings. I would like to highlight the meeting HCV treatment in cirrhotic patients lectured by Professor Graham Foster (professor of Hepatology at Queen Mary University of London and consultant at Barts Health Trust). Globally, this programme had far exceeded my expectations and I am convicted that this award will have a wider impact on my career. As one of the first five participants in the UEG Visiting Fellowship Programme, I hope now I will have more opportunities to engage in other UEG activities and other several scientific societies. Finally, I would like to outline that the Radboud Medical Center Gastroenterology team was very supportive of me and made me feel at home. Those were weeks full of knowledge that improved my skills as a gastroenterologist. I am very grateful to Professors Drenth and Siersema. They are brilliant doctors and scientists and wonderful people who always kept me motivated and transmitted to me their passion for gastroenterology. I would also like to gratefully thank the UEG Young Talent Group for the Travel award granted that was helpful in lodgement and travel expenses. I definitely recommend UEG Visiting Fellowship Programme to every young gastroenterologist as an opportunity for collaboration and networking in gastroenterology, which will, undoubtedly, enrich their career development!

Leadership roles for women in gastroenterology: New initiatives for the new generation of gastroenterologists

In many of our medical schools throughout Europe there are now more female than male trainees, and women are entering a wide range of specialities including gastroenterology, gastrointestinal (GI) surgery as well as radiology and pathology. Furthermore, a significant proportion of women are making major contributions to research and teaching in GIrelated specialties. As well as meeting service demands and performing research tasks, there are important leadership roles in gastroenterology. These roles include opportunities to take part in local, national and international discussions about how to improve organisation and training within the specialty, and to put forward the case to help maximise funding to improve health outcomes for GI diseases. Whilst the opportunities can be exciting, leadership comes with increasing demands which are often outside of the expected working hours. For many men and women opportunities for leadership coincide with a large workload and responsibilities for caring for their children and elderly parents. As a result, difficult choices arise as to whether to take on important positions in one’s own department, or as a member of national and international societies and within policy boards including government. United European Gastroenterology (UEG) is waking up to the fact that the contributions of women in their boards and committees do not reflect the changing face of medicine internationally. In 2015, only 12% of representatives to UEG’s boards and committees were women, and a female UEG president is yet to be appointed. The UEG would like to ensure that women are nominated for these positions and that they are supported by their departments when they are elected. To help ensure that opportunities are there for women in the UEG an Equality and Diversity Group (E&D Group) has been created, with the main aim of ensuring equal opportunities for its members and recognising individual values and expertise. One example of a practical suggestion made by the E&D Group is that the age limits for grants and prizes should take into account time spent on maternity leave or caring for family members. As a result of this suggestion the UEG Council has agreed that applications for grants and prizes with an age limit should be adjusted to allow for an additional two years for each child for which the applicant has been the main carer (whether male or female). The E&D Group continues to meet and make recommendations to Council in order to promote equality (including, but not restricted to, gender equality) in gastroenterology leadership and to help fulfil the aspirations of young female members. UEG is continuously seeking to provide outstanding opportunities for training and mentorship for trainees. Examples include the Summer School, the Young Investigator Meeting, basic research courses and many opportunities during the UEG week itself. Last year, for the first time, we held a lively discussion forum in the poster and exhibit area about how to maintain a work-life balance. This year the Women in GI will host a Hotspot Session at UEG week entitled ‘A survivor’s guide for a happy and successful career in Gastroenterology’ and there will be a ‘Career chat’ in the Young GI Lounge. We hope that by airing the practical issues for men and women in gastroenterology we will help to inspire and encourage each other about how to combine aspirations in our personal life with the pressures and opportunities at work. Young gastroenterologists have more opportunities today than ever before and there are role models to help guide you whatever your aspirations. Although there are areas that are traditionally dominated by males, like upper GI surgery and interventional endoscopy, women experts in this field would like to encourage young female gastroenterologists to embark on this career path. We hope that many of our members will take the opportunities afforded by UEG to improve their leadership skills by finding the right mentor, participating in workshops and courses, applying for fellowships and getting involved in the activities of national and international societies. Do not wait to be asked – put yourself forward and you will be surprised about what you can gain from the experience.