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Background Data on the outcomes of surgery due to IBD in pregnant patients is scarce, and primarily dates back more than 3 decades ago. Primary aim: to evaluate the evolution of pregnancies and offspring after surgery due to IBD. Secondary aims: to describe the indications for surgery, the surgical techniques used, and the frequency of caesarean section concomitant to surgery for IBD Methods SCAR is a retrospective, multicenter study approved by ECCO COllaborative Network For Exceptionally Rare Case Reports (CONFER). Patients operated on due to IBD during pregnancy after 1998 (first biologic agent approved) were included. Data on patients’ demographics, IBD characteristics, medical treatments, IBD activity, pregnancy outcomes, surgery, delivery, foetal and maternal outcomes, were recorded Results 44 IBD patients were included (figure 1), all singleton pregnancies. Seven patients (16%) were diagnosed with IBD during pregnancy, 75% had Crohn’s disease (51% fistulizing behavior), and 23% had ulcerative colitis. 34% had previously undergone surgery due to IBD. Several complementary examinations were performed during pregnancy without complications (figure 2) Patients were being administered the following medications: corticosteroids (61%), biologicals (57%), thiopurines (23%) with 20% being on biologics and thiopurines. 93% of surgeries were performed in University hospitals, (2nd Trimester: 55%; 3rd trimester: 27%) with 77% of them being urgent surgeries (figure 3) One patient had hemoperitoneum during surgery, and 27% had postsurgical complications. No woman died. 62.5% of deliveries were induced (figure 4), 70% of them by C-section, with 51% of mothers having a prolonged hospitalization. There were 40 newborns alive and 4 miscarriages/stillbirths (1 in the 1st, 2 in the 2nd, and 1 in the 3rd trimester): 2 occurred during surgery and 2 occurred 2 weeks after surgery. 14% of the surgeries during the 2nd trimester and 64% of those in the 3rd trimester ended up with a simultaneous C-section or delivery. Of the 40 newborns alive, there were 9 healthy (24%), 61% premature, and 47% with low birth weight. A total of 42% of newborns needed hospitalization (25% in the intensive care unit, mainly due to respiratory distress) Conclusion The need for surgery for IBD during pregnancy remains an extremely serious situation. Maternal and foetal mortality are lower than previously described, most likely due to better supporting care. However, even in the current years, 30% of the mothers and 80% of newborns have complications, and 25% of the offspring need admission to the intensive care unit. Therefore, surgical management should be performed by a multidisciplinary team, involving gastroenterologists, colorectal surgeons, obstetricians and neonatal specialists.

Background Hidradenitis suppurativa (HS) is a chronic, recurrent inflammatory disease affecting skin that bears apocrine glands and is characterised by painful, deep-seated, inflamed lesions. Treatment includes antibiotics, steroids, surgery, and adalimumab as the only approved biological agent. An association between inflammatory bowel disease (IBD) and HS has been reported, but very limited evidence exists on the efficacy of non-anti-TNF biological agents for the treatment of HS in IBD patients. Methods This multicenter case series was performed as part of the Collaborative Network of Exceptionally Rare case reports (CONFER) project by ECCO. Cases of patients with HS and IBD treated with non-anti-TNF biological agents were retrospectively collected through a standardised collection form. Efficacy measures were reported by the local gastroenterologist/dermatologist using physician global assessment (PGA). Results Fifty-five patients (65.5% women, median [IQR] age 40.0 [33.1-47.6] years, 50.9% active smokers) were identified (Table 1), all with HS diagnosis confirmed by a dermatologist. We observed a strong CD predominance (90.9%) in the current cohort. HS affected mainly the inguinal (82.0%) and axillary (76.0%) regions, followed by the anogenital region (46.0%). In 42 patients, HS was diagnosed a median of 10.0 [4.3-16.4] years after the IBD diagnosis, whereas in 13 HS preceded the IBD diagnosis by 4.1 [2.2-5.4] years. Prior to initiating a non-anti-TNF biological agent, all patients had been exposed to at least 1 anti-TNF agent, including (high dose) adalimumab in 83.2% of the cases. In 20% of patients, HS developed while being treated with an anti-TNF agent. After anti-TNF failure (for either IBD and/or HS), physicians opted for ustekinumab (83.6%), vedolizumab (14.5%), or risankizumab (1.8%) as the preferred first non-anti-TNF agent. During ustekinumab treatment (n=46, median time on therapy 2.1 [0.8-3.3] years)), 76.1% showed a clinically relevant HS improvement (including 50.0% complete remission), whereas 23.9% did not experience any benefit. With vedolizumab (n=8), 37.5% experienced some benefit (including 25.0% with complete remission), while 62.5% did not report any improvement. The single patient on risankizumab had complete remission. Finally, 6 out of 8 vedolizumab-treated patients were ultimately treated with ustekinumab, reporting a clinical benefit in 5 out of 6. Conclusion Ustekinumab is the preferred biological agent after anti-TNF failure in IBD patients with concomitant HS. Although placebo-controlled trials are lacking and ustekinumab is not approved for the treatment of HS, the current multi-centre case series demonstrates a substantial benefit in 78.4% of patients.

Background To gain insight into vedolizumab (VEDO) use as a first-line biologic in Crohn′s disease (CD), this comparative, two-arm prospective real-world-evidence (RWE) study with propensity score (PS) adjustment aimed to assess, within the maintenance phase, the 2-year comparative effectiveness and persistence of VEDO vs anti-TNF therapy in biologic-naïve CD patients. Methods Between 2017-2020, 1200 consecutively enrolled biologic-naïve and biologic-experienced patients with ulcerative colitis (UC) and CD were prospectively included in the VEDOIBD study from 45 IBD-experienced centres across Germany. 260 biologic-naïve CD patients starting a new therapy with VEDO or anti-TNF were included in this RWE comparison of VEDO vs anti-TNF. The Kaplan-Meier curve was used to summarize the treatment persistence from the start of therapy through week-104. The primary outcome was two-year clinical remission (HBI ≤ 4). Patients were analysed on a modified intent-to-treat basis (mITT; switchers considered as outcome failure). To reduce the effect of confounders, PS adjustment with inverse probability of treatment weighting (IPTW) was implemented. A weighted logistic regression was used to evaluate the effectiveness. The results were reported as odds ratio (OR) and 95% confidence interval (CI). Results 63 VEDO and 197 anti-TNF (ADA: 58.4%, IFX: 41.6%) biologic-naïve CD-patients were evaluated. Two years after treatment initiation approximately 83% of VEDO patients were still in continuous treatment vs only 56% of anti-TNF patients (Fig. 1). In the mITT analysis (Fig. 2), there was a significantly higher clinical remission rate with VEDO when compared to anti-TNF after two years (VEDO: 64.2% vs anti-TNF: 44.7%), and a higher steroid-free remission (VEDO: 62.5% vs anti-TNF: 41.6%). Both differences were statistically significant (p Conclusion Compared to previous RCTs, this prospective two-year RWE study comparing VEDO with anti-TNF showed that, in biologic-naïve CD patients, remission rates at two years with VEDO were remarkably higher than with anti-TNF. Given the favourable side effect profile of VEDO, these findings may aid physicians’ decision-making on the choice of VEDO as a first-line biologic for CD.

Background Since April 2020, vedolizumab (VEDO) has been available for use in IBD in intravenous (iv) and subcutaneous (sc) formulations. Due to limited data on real-world use and effectiveness, the objectives of this real-world evidence (RWE), observational, prospective study are to observe (1) the time point of conversion to VEDO sc, (2) the 6-month remission rate with VEDO sc. using data from the VEDOIBD study. Methods Between 2017-2020, 1200 consecutively enrolled patients with ulcerative colitis (UC) and Crohn’s disease (CD) were prospectively included in the VEDOIBD study from 45 IBD-experienced centers across Germany. Additionally, 74 VEDO-naïve patients were included with the goal of conversion to VEDO sc after an iv-induction period with VEDO (VEDO iv week 0, 2, 6). Effectiveness was measured by clinical remission (HBI ≤ 4) at month 6. Results A total of 180 IBD patients with a running VEDO iv therapy were converted to VEDO sc during the entire study, with at least one 6-month visit from 119 patients (UC: n=67; CD: n=52). Characteristics are shown in Table 1. 87 IBD patients (73.1%) were still receiving VEDO sc after 6 months. 32 IBD patients (26.9%) stopped VEDO sc therapy within the first 6 months. The majority of patients returned to treatment with VEDO iv (37.9%) and the others switched to other biologics: 24.1% ustekinumab, 34.5% anti-TNF (Figure 1). At the time of conversion to sc, 92 patients (77.3%) were in remission (UC: 75%; CD: 84.6%). Of those, 88% remained in remission at 6 months (UC: 89.6%; CD: 86.4%). 45.8% of patients not in remission at the time of conversion to VEDO sc were in remission at 6 months (UC: 50%; CD: 37.5%). Of the 74 patients with planned conversion to VEDO sc, 52 patients (70.3%) received VEDO sc as planned previously: 11.5% within the first 2 weeks, 42.3% after week 6, 19.2% after week 14, and 26.8% after six months or later. Conclusion IBD patients with a conversion from VEDO iv to VEDO sc show high effectiveness after 6 months; conversion usually was carried out between 6 and 14 weeks. Based on these data, VEDO sc is shown to be an effective alternative to VEDO iv in RWE and should therefore be considered an important option in treatment planning and discussion with patients.

ZusammenfassungDie COVID-19-Pandemie ist ein weltweiter Ausbruch von neu aufgetretenen Infektionen mit dem SARS-CoV-2-Virus, von denen weltweit derzeit mehr als 10.670.000 Menschen erkrankt sind bzw. waren. In Deutschland leiden ca. 450.000 Patienten an einer chronisch entzündlichen Darmerkrankung; diese Patienten benötigen in der Regel eine kontinuierliche und kompetente Betreuung. Vor dem Hintergrund eines rasch zunehmenden Wissenszuwachses haben 68 Experten, die die derzeit gültigen Leitlinien der DGVS zum Morbus Crohn und zur Colitis ulcerosa erstellt haben, im Rahmen einer virtuellen Konferenz aktuelle und praxisnahe Empfehlungen formuliert, um die Versorgung von CED-Patienten zu verbessern. Diese adressieren das Infektionsrisiko einschließlich des Risikos für besondere Gruppen, den möglichen Verlauf der Erkrankung und die Konsequenzen für die medikamentöse und die operative Therapie der Grunderkrankung sowie allgemeine Maßnahmen zur Infektionsprävention und adjuvante Präventions- und Therapiemöglichkeiten.

Background Within the framework of the prospective real-world RUN-CD registry on the effectiveness and safety of ustekinumab (UST) in Crohn’s disease (CD), a total of 901 CD-patients undergoing a newly initiated biologics therapy were enrolled in 44 IBD-experienced centers from all over Germany between 2017-2020 with a follow-up of 3 years. Here, the results on the effectiveness of the maintenance therapy over 24 months are presented as a real-world evidence (RWE) comparison of CD-patients with UST vs anti-TNF. Methods After exclusion of other biologics than UST and anti-TNF and missing outcomes (HBI), the final sample consisted of 550 CD patients. Clinical remission (HBI ≤ 4) was the predefined endpoint at month 24 and additionally, switching of biologics therapy was considered as an outcome failure. Patients were analysed on a modified intent-to-treat basis (mITT; switchers considered as outcome failure). To reduce the effect of confounders, propensity score (PS) adjustment with inverse probability of treatment weighting (IPTW) was implemented. A weighted logistic regression was used, and the results were reported as odds ratio (OR) and 95% confidence interval (CI). Quality of life was assessed using the self-reported visual analogue scale (EQ-VAS) of the EQ-5D with changes from baseline to 2 years. Results 308 UST (naïve: 27) and 242 anti-TNF (naïve: 162) CD-patients were included (ADA: 61.2%, IFX: 38.8%). The number of switches within 24 months was significantly lower with UST than with anti-TNF (27.6% vs 37.1%; p=0.038), and especially with IFX, whereby the difference between UST and IFX (27.6% vs 46.7%; p=0.003) proves to be statistically significant (Fig. 1). Clinical remission at two years was not statistically different for the overall UST vs anti-TNF groups (51.2% vs 54.4) (numerically higher in biologic-naïve UST- vs anti-TNF-patients, without statistically significance) (Tab. 1). Remission rates were similar for UST vs ADA, while they were significantly higher for UST vs IFX (54.4% vs 37.9%; p=0.008) (Tab. 2), and also significantly higher for ADA vs. IFX (58.2% vs 37.9%; p=0.003). As a sign of an improved QoL we observed a significant increase in EQ-VAS within both treatment groups. However, a similar increase in EQ-VAS was observed with UST and anti-TNF (+14.2 vs +12.3; p=0.147). Conclusion In this prospective two-year RWE comparison clinical remission was, also due to more frequent switches within the IFX group, significantly higher with UST when compared with IFX and higher with ADA than with IFX. Considering the effectiveness results of UST and the proven favourable safety profile, UST can be considered a first-line targeted therapy for CD.

Background To gain insight into vedolizumab (VDZ) use as a first-line biologic in Crohn′s Disease (CD), this real-world study aimed to assess, within the maintenance phase, the 1-year comparative effectiveness and persistence of VDZ vs anti-TNF therapy in biologic-naïve CD-patients. Methods Between 2017–2020, 1200 consecutively enrolled biologic-naïve and biologic-experienced patients with ulcerative colitis (UC) and CD were prospectively included in the VEDOIBD-Registry from 45 IBD-experienced centres across Germany. 294 biologic-naïve CD-patients starting a new therapy with VDZ or anti-TNF (adalimumab: ADA or infliximab: IFX) were included in this real-world evidence (RWE) study. The Kaplan-Meier was used to summarize the treatment persistence from the start of therapy through week-52. The primary outcome was week-52 clinical remission (HBI ≤ 4). Patients were analyzed on a modified intent-to-treat basis (mITT; switchers considered as outcome failure) and on a per-protocol (PP) basis (excluding switchers). To reduce selection bias in the estimation of treatment effects, the inverse probability of treatment weighting propensity score (PS) was implemented. A weighted logistic regression was used to evaluate the effectiveness. The results were reported as odds ratio (OR) and 95% confidence interval (CI). Results 71 VDZ and 223 anti-TNF (ADA: 59.6%, IFX: 40.4%) biologic-naïve CD-patients were evaluated. 52-weeks after treatment initiation approximately 94% of VDZ patients were still in continuous treatment vs 75% of ADA and 78% of IFX (Figure 1). The mITT 1-year clinical remission rate was 76.1% for VDZ vs 63.8% for anti-TNF (OR: 1.80, 95% CI: 0.86–3.76). Similar results were observed for VDZ vs IFX (Table 1). In contrast, the clinical remission was significantly higher in the VDZ group than in the ADA group (OR: 2.24, 95% CI: 1.04–4.85). The PP analysis suggested comparative effectiveness, having excluded more anti-TNF switchers. 91.7% of week-14 responders VDZ patients were in clinical remission from week 14 through 52 vs 66.1% of anti-TNF patients (OR: 5.69, 95% CI: 1.66–19.5). Similar, significant, results were observed for VDZ vs ADA and for VDZ vs IFX (Table 2). Conclusion In this real-world setting comparing VDZ and anti-TNF in biologic-naïve patients via PS weighted analysis, VDZ showed especially in week-14 responders higher clinical remission rates in comparison to anti-TNF. The higher treatment persistence observed for VDZ, perhaps due to a more favourable safety profile vs anti-TNF, may be considered the main driver for the better effectiveness of VDZ at one year. These findings may aid physicians’ decision-making on the choice of VDZ as the first-line biologic for CD.

Background Observational real world studies are required in addition to RCTs which typically represent selected patients not reflecting everyday clinical practice. Between 2017–2020 patients with Crohn’s disease (CD) receiving a newly initiated biologics therapy were consecutively enrolled into the prospective, observational RUN-CD registry from 44 IBD-experienced German centres to assess effectiveness and safety of ustekinumab (UST) with a 3 years follow-up. Here, the results on the effectiveness of the maintenance therapy over 12 months are presented as a real world evidence (RWE) comparison of UST vs anti-TNF. Methods After exclusion of other biologics than UST and anti-TNF and missing outcomes, the final sample consisted of 607 CD-patients. Clinical remission (HBI ≤ 4) was the predefined endpoint at month 12. Patients were analyzed on a modified intent-to-treat basis (mITT; switchers considered as outcome failure). To reduce the effect of confounders, propensity score (PS) adjustment with inverse probability of treatment weighting (IPTW) was implemented. A weighted logistic regression was used, and the results were reported as odds ratio (OR) and 95% confidence interval (CI). Results 343 UST (naïve: 35) and 264 anti-TNF (naïve: 175) (ADA 61%, IFX 39%) CD-patients were included. PS removed systematic differences between both groups (mean of both groups: 15% perianal disease, 36% surgical resection, 41% EIM). Overall, the number of switches was lower in the UST group than in the anti-TNF group (Tab. 1). However, the number of switches within 12 months was significantly lower in the UST group only when compared to the IFX group (16.3% vs 27.2%; p=0.045) (Fig. 1). Clinical remission rates at 1 year (Tab. 2) were not statistically different for the overall UST vs. anti-TNF groups (65.8% vs 60.0%). Remission rates were similar for UST vs ADA, while these were significantly higher for UST vs. IFX (61.6% vs 41.8%; p=0.009). Looking at clinical remission in the week 16 responder group (Tab. 3), a statistically significantly higher remission rate was found in the overall group for UST (77.6%) vs anti-TNF (65.4%) (p=0.041), which was mainly driven by the higher UST remission rate in biologic-naïve CD patients (p=0.026). Conclusion This 1-year maintenance phase RWE-comparison with UST vs anti-TNF showed remarkably high clinical remission rates in both groups. Also due to a more frequent switching within the IFX group, the clinical remission rate at 1 year was significantly higher with UST than with IFX and higher with UST vs anti-TNF in the biologic-naïve groups. These results support together with the known favorable safety profile consideration of UST as a first-line targeted therapy for CD.

Background Hereditary colorectal cancer syndromes (HCCS) are rare polyposis or nonpolyposis syndromes with a higher risk of developing colorectal cancer (CRC). Coexisting inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), with HCCS is exceedingly rare and presumably increases the risk of early-onset colorectal cancer. Methods This was a multicenter case series performed as a part of the European Crohn’s and Colitis Organisation (ECCO) Collaborative Network of Exceptionally Rare case reports (CONFER) project. Results This report includes 26 patients with IBD (10 UC, 15 CD, and one with IBD unclassified (IBD-U)) and concomitant HCCS. Among these 26 patients (median age 33 years, IQR 20–44), 15 (57.7%) were males, 24 (92.3%) Caucasians and 2 (7.7%) of Arab origin. Among patients with UC, 4 (40%) had proctitis, 3 (30%) left-sided colitis and 3 (30%) an extensive disease; while, among patients with CD, 8 (53.3%) had ileal, 5 (33.3%) ileocolonic, 2 (13.3%) colonic disease. One of these patients had ileocolonic disease associated with upper disease location and six (40%) had an associated perianal disease. Many of patients with CD had a non-stricturing non-penetrating phenotype (53.3%, n=8), while 20.0% (n=3) and 26.7% (n=4) had a stricturing or penetrating phenotype, respectively. HCCS was diagnosed before the IBD diagnosis in 11 patients (42.3%), after diagnosis of IBD in 11 patients (42.3%) and concurrently in 4 patients (15.4%). Sixteen patients had Lynch syndrome, 7 had FAP, 2 had AFAP and one had MAP. The most frequent genetic mutations were those of APC (n=7) and MLH1 (n= 7). Thirteen patients were treated with immunomodulatory (IMM) therapy. During IMM therapy, only 5 patients developed drug-induced side-effects which did not require drug interruption. One patient treated with vedolizumab developed CRC, despite yearly colonoscopy surveillance, after 4 years of treatment. Overall, CRC developed in 38.5% of patients (n=10): in 5 patients (50%) after IBD diagnosis, in 4 (40%) patients before IBD diagnosis, and in 1 patient the 2 conditions were diagnosed simultaneously. Eighteen (69.2%) patients underwent colectomy or abdominal surgery: 9 patients due to CRC diagnosis, 7 patients preventively due to the underlying HCCS and 2 patients because of active IBD disease. On follow-up, one patient died due to CRC. Conclusion This case series describes the largest series to date of patients with IBD patients and HCCS, with special emphasis on the use of IMM in this population. The most frequent diagnosis of HCCS associated with IBD was Lynch syndrome. These data demonstrate the high malignancy rate and surgical intervention rate in this IBD cohort. The optimal medical approach still needs to be addressed.

Die laparoskopische restaurative Proktokolektomie mit ileopouchanaler Anastomose (IPAA) stellt eine kurative Behandlungsoption der therapierefraktaren Colitis ulcerosa (CU) dar. Das zweizeitige Vorgehen mit Anlage eines doppellaufigen, protektiven Ileostomas ist die haufigste gewahlte Variante. Ziel des chirurgischen Eingriffs ist die komplette Entfernung des Kolons und Rektums mit gleichzeitiger Wiederherstellung der gastrointestinalen Kontinuitat und Erhalt der Kontinenzfunktion. Die langfristige Lebensqualitat nach laparoskopischer Proktokolektomie mit IPAA ist gut und vergleichbar mit der einer gesunden Vergleichspopulation. Anhand eines Operationsvideos, welches online zur Verfugung steht, wird die Operationstechnik detailliert dargestellt.

Restorative proctocolectomy with an ileoanal pouch anastomosis (IAPA) is the surgical therapy of choice for patients with refractory ulcerative colitis and/or associated (pre)neoplastic lesions. It is predominantly performed laparoscopically. Reconstruction with a J‑pouch is the most frequently applied variant due to the ideal combination of technical simplicity and good long-term results. In the present review, potential postoperative pouch complications, their risk factors, diagnostics and surgical management, as well as mid-term and long-term quality of life after pouch construction are differentially presented based on the current literature.

Laparoscopic restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) constitutes a curative treatment option for therapy-refractory ulcerative colitis. A two-stage procedure with loop ileostomy at the time of IPAA is the most frequent variant of surgery. The aim of the procedure is the complete removal of the colon and rectum with simultaneous restoration of gastrointestinal continuity and preservation of continence functions. Long-term quality of life following laparoscopic proctocolectomy with IPAA is good and comparable with a healthy reference population. The surgical technique is demonstrated in detail with the help of a video of the operation, which is available online.

Restorative proctocolectomy with an ileoanal pouch anastomosis (IAPA) is the surgical therapy of choice for patients with refractory ulcerative colitis and/or associated (pre)neoplastic lesions. It is predominantly performed laparoscopically. Reconstruction with a J‑pouch is the most frequently applied variant due to the ideal combination of technical simplicity and good long-term results. In the present review, potential postoperative pouch complications, their risk factors, diagnostics and surgical management, as well as mid-term and long-term quality of life after pouch construction are differentially presented based on the current literature.

Objective: The aim of this study was to develop a new international classification of acute pancreatitis severity on the basis of a sound conceptual framework, comprehensive review of published evidence, and worldwide consultation. Background: The Atlanta definitions of acute pancreatitis severity are ingrained in the lexicon of pancreatologists but suboptimal because these definitions are based on empiric descriptions of occurrences that are merely associated with severity. Methods: A personal invitation to contribute to the development of a new international classification of acute pancreatitis severity was sent to all surgeons, gastroenterologists, internists, intensive medicine specialists, and radiologists who are currently active in clinical research on acute pancreatitis. The invitation was not limited to members of certain associations or residents of certain countries. A global Web-based survey was conducted and a dedicated international symposium was organised to bring contributors from different disciplines together and discuss the concept and definitions. Result: The new international classification is based on the actual local and systemic determinants of severity, rather than descriptions of events that are correlated with severity. The local determinant relates to whether there is (peri)-pancreatic necrosis or not, and if present, whether it is sterile or infected. The systemic determinant relates to whether there is organ failure or not, and if present, whether it is transient or persistent. The presence of one determinant can modify the effect of another such that the presence of both infected (peri) pancreatic necrosis and persistent organ failure have a greater effect on severity than either determinant alone. The derivation of a classification based on the above principles results in 4 categories of severity - mild, moderate, severe, and critical. Conclusions: This classification is the result of a consultative process amongst pancreatologists from 49 countries spanning North America, South America, Europe, Asia, Oceania, and Africa. It provides a set of concise up-to-date definitions of all the main entities pertinent to classifying the severity of acute pancreatitis in clinical practice and research. This ensures that the determinant-based classification can be used in a uniform manner throughout the world.

Im Jahr 1998 wurde der erste TNF-Blocker in den USA und ein Jahr spater auch in Deutschland zugelassen. Die Therapie mit TNF-Blockern hat die Therapiemoglichkeiten von Patienten mit chronisch-entzundlichen Erkrankungen in Rheumatologie, Dermatologie und Gastroenterologie deutlich erweitert. Es ist aber nicht immer moglich, durch systemisch applizierte TNF-Blocker eine lokale klinische Besserung der jeweiligen Grundkrankheit zu erreichen. Daher gab es in den letzten Jahren vielfaltige Ansatze einer topischen Therapie mit TNF-Blockern. Das wichtigste Ziel dieser off-label-Anwendungen ist die Applikation einer groseren Menge des TNF-Blockers im entzundeten Gewebe, als dies mit einer systemischen Therapie erreichbar ware. Diese Ubersicht gibt einen Uberblick uber die Vielfalt der bislang erfolgten topischen Therapieversuche mit TNF-Blockern.

Errors in fluid management can lead to significant morbidity in children. We conducted an experimental animal study to determine the margin of safety in accidental hyperinfusion of different glucose and electrolyte containing solutions.Fifteen piglets [bodyweight 12.1 (sd 2.0) kg] were randomly assigned to receive either 100 ml kg⁻¹ of balanced electrolyte solution with glucose 1% (BS-G1), hypotonic electrolyte solution with glucose 5% (HE-G5), or glucose 40% solution (G40) over 1 h. Blood electrolytes, glucose, and osmolality and intracranial pressure (ICP) were measured before, during, and after fluid administration.Hyperinfusion of BS-G1 led to moderate hyperglycaemia [baseline 3.4 (sd 1.3) mmol litre⁻¹, study end 12.6 (1.8) mmol litre⁻¹], but no other relevant pathophysiological alterations. Hyperinfusion of HE-G5 produced marked hyperglycaemia [baseline 3.9 (1.2) mmol litre⁻¹, study end 48.6 (4.3) mmol litre⁻¹, P0.05] and hyponatraemia [baseline 136.4 (1.3) mmol litre(-1), study end 119.6 (2.1) mmol litre⁻¹, P0.05], whereas osmolality remained stable during the course of the study. Hyperinfusion of G40 induced acute hyperglycaemic/hyperosmolar decompensation with an extreme decrease in serum electrolytes [e.g. sodium baseline 138 (1.1) mmol litre⁻¹, 30 min 87.8 (6.4) mmol litre⁻¹, P0.01], leading to cardiac arrest after infusion of 50-75 ml kg⁻¹. ICP remained within a physiological range in all groups.In an animal model of accidental hyperinfusion, BS-G1 showed the widest margin of safety and can therefore be expected to enhance patient safety in perioperative fluid management in children; HE-G5 proved significantly less safe; and G40 was found to be outright hazardous.

Die akute Pankreatitis ist eine potenziell todlich verlaufende Erkrankung, die mit steigendem Schweregrad eine zunehmend individualisierte Therapie erfordert. Die Diagnose der akuten Pankreatitis beruht auf der Anamnese, der klinischen Untersuchung sowie einer sinnvoll eingesetzten Bildgebung und Labordiagnostik. Jeder Patient mit akuter Pankreatitis muss stationar aufgenommen werden, da der Krankheitsverlauf bei Erstvorstellung des Patienten nicht abgeschatzt werden kann. Wichtigstes therapeutisches Element ist die rasche intravenose Substitution von Flussigkeit und Elektrolyten, begleitet von einer suffizienten Schmerztherapie. Hier sind meist Opiatanalgetika erforderlich. Pankreatitisspezifische Therapieansatze haben sich bislang als wirkungslos erwiesen. Die Rolle der Antibiotika- und Ernahrungstherapie hat in den letzten Jahren eine umfassende Neubewertung erfahren. Eine Operation oder eine endoskopische Intervention kann bei schwer kranken Patienten im Einzelfall sinnvoll sein. In dieser Ubersichtsarbeit fassen wir klinisch relevante Aspekte der Diagnostik und Therapie der akuten Pankreatitis zusammen.

Nutritional concepts in acute pancreatitis are undergoing a rapid change. An early start of nutrition via nasojejunal tubes is about to replace parenteral nutrition. Yesterday it was believed that the pancreas had to be put at rest. Thus, stimulation of pancreatic secretion by enteral nutrition was believed to be detrimental. However, on comparing the results of enteral with those of parenteral nutrition, the pancreatic infection rates, rate of surgical interventions, days of hospital stay, and costs are found to be significantly reduced. Whether or not enteral nutrition decreases mortality has not been clearly proven. Pancreatitis is associated with the risk of paralytic ileus. Thus, data suggesting that one does not have to feed via a nasojejunal tube but rather via an easier to place nasogastric tube, are provocative. Numerous questions still have to be answered such as composition of tube diet, nutrition in mild to moderate pancreatitis, ways to reduce pain and composition of diet when oral refeeding is started. The nutrition of tomorrow may implicate immunonutrition. There are only a few small studies suggesting beneficial effects by supplementation of tube feeding with MCT/LCT triglycerides, glutamine, arginin, omega-3-fatty acids, nucleotides. So far, these supplements have failed to show efficacy for clinically relevant endpoints. In an recently published study, prebiotics were associated with a high complication rate. In this review, we summarise the current knowledge on nutrition in acute pancreatitis and discuss future developments.

Malignome des Gastrointestinaltrakts stellen zusammengenommen die haufigste krebsbedingte Todesursache in Deutschland dar. Die Morbiditat durch diese Erkrankungen ist erheblich. Trotz der Fortschritte in der chirurgischen und medikamentosen Therapie gastrointestinaler Malignome besteht im fortgeschrittenen Stadium in der Regel keine Heilungsmoglichkeit mehr. Praventionsmasnahmen und Screening konnen die Letalitat durch diese Karzinome senken. Vermeidung von Ubergewicht bzw. Gewichtsabnahme sowie Nikotinkarenz sind effektive vorbeugende Masnahmen bei Osophagus-, Pankreas- und kolorektalem Karzinom. Behandlung von Infektionen durch Hepatitisviren und Helicobacter pylori schutzt vor hepatozellularem Karzinom bzw. Magenkarzinom. Das beste Beispiel fur eine wirksame Vorsorgeuntersuchung ist die Koloskopie. Durch die Koloskopie konnen kolorektale Adenome und Karzinome fruhzeitig entdeckt, Adenome als Prakanzerosen endoskopisch in gleicher Sitzung entfernt werden. Der Einsatz einfacher Praventionsstrategien und effizienter Vorsorgemasnahmen bei gastrointestinalen Malignomen wird im vorliegenden Beitrag praxisnah erlautert.

Ein 32-jahriger Patient stellte sich aufgrund von akutem Brechdurchfall in unserem Klinikum vor. Leichtere Durchfalle, gelegentlich auch mit Blutbeimengungen bestanden bereits seit mehreren Jahren. Zum Zeitpunkt der Vorstellung war der Patient auserdem anurisch. Nach Ausschluss eines pra- und postrenalen Nierenversagens erfolgte eine Nierenbiopsie. Die histologische Aufarbeitung der Nierenbiopsie zeigte Veranderungen, die auf ein hamolytisch-uramisches Syndrom hinweisen. Fur eine Glomerulonephritis im Rahmen einer Vaskulitis gab es keinen Anhalt. Als Ursache fur den Durchfall und die Erregereintrittspforte ist bei typischer Bildgebung auch ohne histologischen Nachweis ein M. Crohn anzusehen. Wir berichteten damit erstmals von einem hamolytisch-uramischen Syndrom als Erstmanifestation eines M. Crohn.

BACKGROUND AND OBJECTIVE Sudden cardiac death is a leading cause of death. In Germany, only 10% of patients will survive reanimation. The prognosis is mainly determined by the first-aid skills of accidental witnesses. METHODS The reaction of 1007 German-speaking adults (462 males, 545 females, median age 39 years) was investigated in an emergency scenario with symptoms of sudden cardiac death in an acquaintance. Afterwards a self-assessment of their first-aid skills, such as cardiac compression and mouth-to-mouth ventilation was made. RESULTS 94% of the interviewees would call professional aid at once. Diagnostic skills, as searching for pulse or checking for breath would be done by 26 and 21%, respectively. The most frequently mentioned therapeutic skill was positioning the victim in stable lateral position (37%), but very less frequently cardiac compression (6%) and mouth-to-mouth resuscitation (10%). When asked, 51 (81%) of those interviewed regarded their skills in cardiac compression and mouth-to-mouth resuscitation as adequate. To some extent there were differences in favor of young people and those from East Germany. CONCLUSION These representative data suggest that (a) ABC-like first-aid rules are largely unknown among the population; (b) the value of a stable lateral position is overestimated and (c) first-aid skills of elderly persons are worst. A significant improvement of first-aid skills of the German population is mandatory in order to improve in future the outcome of sudden cardiac death.

Summary. The understanding of the pathogenesis of chronic pancreatitis is limited. Several theories (i. e. obstruction hypothesis) were suggested in the past but could not be confirmed by experimental data. As a formal description of the course of the disease, the necrosis-fibrosis concept seems to be very attractive. According to this theory, there is no significant difference in the pathogenesis of acute and chronic pancreatitis. A major step was the identification of mutations of the cationic trypsinogen, the secretory trypsin inhibitor (SPINK 1) and the cystic-fibrosis protein (CFTR) in some patients. Investigation of these mutations may significantly contribute to a better understanding of the pathogenesis of chronic pancreatitis.

In 1998, the first TNF-blocker was approved in the USA and a year later in Germany. Treatment with TNF-blocking agents has significantly expanded therapeutic options for patients with chronic inflammatory diseases in rheumatology, dermatology and gastroenterology. However, it is not always possible to achieve a local clinical improvement by systemically administered TNF-blockers. Many approaches to topical therapy with TNF blockers have been published in recent years. The main objective of these off-label applications is the injection of a larger quantity of TNF-blocker in the inflamed tissue than it is achievable with systemic therapy. This summary provides an overview of the variety of topical therapy trials and reports own experiences in patients with Crohn's disease.

The treatment of patients with inflammatory bowel disease has become more complex in recent years through the introduction of various immunosuppressive agents as well as the approval of monoclonal antibodies. Patients receiving such treatment must be carefully monitored. National and international guidelines define a diagnostic and therapeutic context for the practitioner, but can only partially respond to specific questions on the procedure for individual patients. Within the framework of a project initiated by Abbott entitled "IBD ahead" 34 German IBD experts have elaborated concrete proposals for the utility of clinical symptom assessment, endoscopy and the use of laboratory parameters including foecal markers of inflammation. Furthermore, we discuss the significance of conventional X-rays, computed tomography, ultrasound and magnetic resonance tomography. These recommendations are illustrated by case studies from everyday practice in the participating centres.

The treatment of patients with inflammatory bowel disease has become more complex in recent years through the introduction of various immunosuppressive agents as well as the approval of monoclonal antibodies against TNF-α and patients receiving such treatment must be carefully monitored. National and international guidelines define a diagnostic and therapeutic context for the practitioner, but can only partially respond to specific questions on the procedure for individual patients. Within the framework of a project initiated by Abbott entitled "IBD ahead" 38 German IBD experts have elaborated concrete proposals for dealing with corticosteroids, immunosuppressants and TNF-α antibodies on the basis of the published literature and their own personal experience in order to close the gap between these guidelines and daily clinical practice. Statements were developed on the choice of correct timing of initiation, dose and duration of the individual substances and on how to proceed with patients exhibiting treatment failure. Moreover, recommendations are also made on drug combination strategies, safety monitoring and the risks regarding the development of infectious complications and malignancies. These recommendations are illustrated by case studies from everyday practice in participating centres.

Pyoderma gangrenosum is the most severe of all cutaneous extraintestinal manifestations seen in inflammatory bowel diseases. One subtype—parastomal pyoderma gangrenosum—is a rare complication of surgery and a particularly demanding task for surgeons, dermatologists, wound care specialists and gastroenterologists. Glucocorticoids and cyclosporine have been mainstays of systemic treatment for pyoderma gangrenosum, although increasing evidence supports the use of biologic therapies, such as tumor necrosis factor inhibitors [1, 2]. Currently no guideline for the treatment of pyoderma gangrenosum exists. Recently, we reported the rapid improvement of refractory pyoderma gangrenosum of the lower limb after topical application of an infliximab gel in a young woman with ulcerative colitis [3]. The refractory course of parastomal pyoderma gangrenosum in a woman with Crohn’s disease stimulated us to investigate topical infliximab therapy. The patient was diagnosed with Crohn’s disease at age 32. Within the first years, she developed several extraintestinal manifestations such as polyarthritis, erythema nodosa and anemia. At initial presentation in our practice in September 2010, she complained of fever and severe abdominal pain which was caused by a large abdominal wall abscess due to a colonic stenosis with a fistula to the abdominal wall. Immediate surgery with partial colonic resection and colostomy was necessary. The patient’s postoperative course was uneventful and she continued azathioprin. A complex rectovaginal fistula was detected during follow-up, which precluded rapid stoma closure. We therefore started infliximab infusions 6 weeks after surgery. In May 2012, when the patient was 48 years old, she detected a small parastomal lesion; histology revealed pyoderma gangrenosum. There was no change after application of topical glucocorticoids. However, the patient reported a marked improvement of pyoderma gangrenosum activity within 10 days after every infliximab infusion but worsening within the next weeks. Dose escalation to 10 mg/kg every 4 weeks did not improve healing, and the patient observed enlargement and bleeding from the lesion. Adalimumab, clobetasol-propionat, gentamycin, topical tacrolimus and several other topic applications were without success, and we continued infliximab infusions with a temporal improvement after infusion. The findings of high tumor necrosis factor concentrations in wound fluid and the success of topical infliximab gel application in chronic venous leg ulcers [4] were rationales for an individual attempt to treat the pyoderma gangrenosum with freshly made infliximab gel as reported recently [3]. However, this gel was difficult to fix aside the stoma bag and did not improve the clinical appearance of the parastomal pyoderma gangrenosum after 3 weeks. Due to the improvement of the pyoderma gangrenosum after infliximab infusion, we suggested a fan-shaped sublesional injection of 100 mg infliximab (dissolved in 10 mL of saline) under the lesion, which caused only slight pain during injection. This was repeated weekly for 3 weeks, but did not result in any improvement after 12-month follow-up (Fig. 1). Sublesional infliximab injection does not seem to be a successful option for patients with parastomal pyoderma gangrenosum. In contrast to pyoderma gangrenosum of leg or face skin, different pathogeneses of sites that are in continuity with the bowel—like parastomal pyoderma N. Teich (&) Internistische Gemeinschaftspraxis fur Verdauungs-und Stoffwechselkrankheiten, Nordstr. 21, 04105 Leipzig, Germany e-mail: teich@igvs.de

Nutritional concepts in acute pancreatitis are undergoing a rapid change. An early start of nutrition via nasojejunal tubes is about to replace parenteral nutrition. Yesterday it was believed that the pancreas had to be put at rest. Thus, stimulation of pancreatic secretion by enteral nutrition was believed to be detrimental. However, on comparing the results of enteral with those of parenteral nutrition, the pancreatic infection rates, rate of surgical interventions, days of hospital stay, and costs are found to be significantly reduced. Whether or not enteral nutrition decreases mortality has not been clearly proven. Pancreatitis is associated with the risk of paralytic ileus. Thus, data suggesting that one does not have to feed via a nasojejunal tube but rather via an easier to place nasogastric tube, are provocative. Numerous questions still have to be answered such as composition of tube diet, nutrition in mild to moderate pancreatitis, ways to reduce pain and composition of diet when oral refeeding is started. The nutrition of tomorrow may implicate immunonutrition. There are only a few small studies suggesting beneficial effects by supplementation of tube feeding with MCT/LCT triglycerides, glutamine, arginin, omega-3-fatty acids, nucleotides. So far, these supplements have failed to show efficacy for clinically relevant endpoints. In an recently published study, prebiotics were associated with a high complication rate. In this review, we summarise the current knowledge on nutrition in acute pancreatitis and discuss future developments.

Acute pancreatitis is potentially fatal. It can be diagnosed based on present history, clinical appearance, and typical findings from laboratory and radiologic investigations. All patients must be admitted to hospital, as the disease course cannot be predicted at initial presentation. Increasing severity demands increasingly individualized therapy. The most important interventions are fast fluid resuscitation and analgesic therapy with opioids. Therapeutic agents specific to pancreatitis have failed to show any advantages so far. The roles of antibiotic therapy and nutritional support in the therapeutic regimen have been profoundly reassessed during recent years. Surgery and endoscopic interventions may be necessary and beneficial in carefully selected patients. In this review we summarize clinically relevant issues of acute pancreatitis.

The pathogenesis of alcohol-induced chronic pancreatitis is still not completely understood. One discusses alcohol-induced fatty degeneration of pancreatic acinar cells, disturbances in ethanol detoxification, reduced synthesis of lithostathines, changes in duct permeability, a pressure increase of the papilla of Vater, generation of free radicals, etc. Hereditary chronic pancreatitis (HCP) is a rare form of early-onset chronic pancreatitis. With the exception of the young age at diagnosis and a slower progression, the clinical course, morphological features, and laboratory findings of HCP do not differ from those of patients with alcoholic chronic pancreatitis. Mutations in the PRSS1 gene, encoding cationic trypsinogen, play a causative role in chronic pancreatitis. It has been shown that the PRSS1 mutations increase autocatalytic conversion of trypsinogen to active trypsin, and thus probably cause premature, intrapancreatic trypsinogen activation disturbing the intrapancreatic balance of proteases and their inhibitors. Other genes, such as the anionic trypsinogen (PRSS2), the serine protease inhibitor, Kazal type 1 (SPINK1), and the cystic fibrosis transmembrane conductance regulator (CFTR) have been found to be associated with chronic pancreatitis (idiopathic and hereditary) as well. The findings in HCP highlight that the protease trypsin seems to play a major role in pathogenesis of chronic pancreatitis.

A 64-year-old man was admitted to our hospital to clarify the aetiology of two delirious episodes which occurred in February and May 2006. Past …

Malignancies of the gastrointestinal tract are the most common causes of cancer-related deaths in Germany. They also induce significant morbidity. Despite both surgical and medical therapeutic improvements, advanced stages of these cancers can rarely be cured. Preventive and screening measures are suitable to decrease gastrointestinal cancer-related mortality. Weight reduction and cessation of smoking are effective in preventing esophageal, pancreatic and colorectal cancer. Treatment of infections like chronic viral hepatitis and helicobacter pylori gastritis is able to protect from hepatocellular and gastric cancer, respectively. Colonoscopy is one of the best established screening methods. It allows early detection of colorectal neoplasia. Preneoplastic adenomas can be endoscopically removed during the same session. We here review simple prevention strategies and effective screening methods in gastrointestinal cancers of relevance in daily practice.

Ulcerative colitis (UC) has traditionally been considered to be an inflammatory disease limited to the colonic mucosa. However, since it has been shown that UC is frequently accompanied by various extraintestinal disorders, there is increasing evidence that UC may also manifest in the nervous system. The following review focuses particularly on these possible manifestations of UC, both in the peripheral (PNS), and in the central nervous system (CNS). A systematic literature search according to the MEDLINE database was performed for this purpose. Although a reliable differentiation may clinically not always be possible, three major pathogenic entities can be differentiated: (i) cerebrovascular disease as a consequence of thrombosis and thromboembolism; (ii) systemic and cerebral vasculitis; (iii) probably immune mediated neuropathy and cerebral demyelination. With the exception of thromboembolism and sensorineural hearing loss, evidence for a causal relationship relies merely on single case reports or retrospective case series. Considering the CNS-manifestations, similarities between UC-associated disorders of the white matter and acute disseminated encephalomyelitis (ADEM) are obvious. Epileptic seizures, unspecified encephalopathies and confusional states are most likely epiphenomena that have to be regarded symptomatic rather than as own entities. A prospective study on the neurologic aspects of UC would be very welcome.

Severe acute pancreatitis leads to a dramatic fluid loss in the intraperitoneal space which may result in circulatory decompensation. Sequestration of fluid can amount up to 40 percent of the circulating blood volume. The amount of fluid and electrolyte replacement is often misjudged leading to a higher rate of complications and a higher mortality rate of the disease. Furthermore, subsequent and adequate fluid resuscitation seems to influence the prognostic course of the disease by improving the perfusion and oxygenation of the pancreas. Otherwise volume overload may cause cardiopulmonary decompensation in the case of synchronous cardiopulmonary comorbidities. Therefore, an important part of treatment relies on careful haemodynamic monitoring, if necessary managed in an intensive care unit. Usually most patients with acute pancreatitis will be treated on a non-intensive medical ward which allows a differentiated and continuous haemodynamic monitoring only to a limited extent. Apart from monitoring circulatory parameters and measuring central venous pressure, there are other clinical methods, laboratory tests and radiological diagnostic procedures to determine the amount of intravascular fluid deficit and the individual volume demand of patients with acute pancreatitis. Prospective clinical trials for evaluation of pancreatitis-specific volume management do not exist so far. The aim of this review is to provide background information on invasive and non-invasive diagnostic methods for detection of circulatory hypovolemia in acute pancreatitis.