Cellular immunotherapies and immune cell depleting therapies in inflammatory bowel diseases: the next magic bullet?

Despite significant advances in biologic and small molecule treatments and the emergence of combination therapies to treat inflammatory bowel diseases (IBD) a large unmet need remains to control intestinal inflammation. New approaches targeting several pathways simultaneously with a favorable safety profile and agents that trigger anti-inflammatory pathways to drive durable resolution of inflammation are needed. This article discusses novel cellular immunotherapies and immune cell depleting therapies in IBD, including CAR-T cell approaches, Tr1 and T regulatory (Treg) cells and cell depleting antibodies such as rosnilimab. These novel approaches have the potential to overcome current therapeutic limitations in the treatment of IBD.

The outcome of patients with inflammatory bowel disease-associated colorectal cancer is not worse than that of patients with sporadic colorectal cancer-a matched-pair analysis of survival.

PURPOSE: Patients with inflammatory bowel disease (IBD) have an increased risk for colorectal cancer (CRC). In IBD patients, cancer is often diagnosed in advanced stages and conflicting data on survival compared to sporadic CRC have been reported. The aim of this study was to directly compare clinical characteristics and prognosis of patients with IBD-CRC and sporadic CRC. METHODS: The clinical and pathological data of 63 patients with IBD-CRC and 3710 patients with sporadic CRC treated at the University Hospital of Erlangen between 1995 and 2015 were compared. Forty-seven M0 patients with IBD were matched with sporadic CRC patients after curative resection (R0) according to tumor localization, stage, sex, and year of treatment. Overall and disease-free survival were compared. RESULTS: Sixty-three patients presented IBD-CRC. Fifty were affected with ulcerative colitis (UC) and 13 with Crohn's disease (CD). CRC was diagnosed within 1.45 years since last endoscopic surveillance. Twelve patients (19%) had a diagnosis of primary sclerosing cholangitis. In matched analysis, IBD patients were diagnosed with CRC at younger age compared to sporadic CRC and were more likely to have right-sided CRC (40% versus 23.3%) and rare histological subtypes (19% versus 9.2%). No differences in 5-year overall (78.7 versus 80.9 months) and 5-year disease-free survival (74.5 versus 70.2 months) were noted. CONCLUSION: IBD-CRC patients were younger and more frequently had right-sided carcinomas compared to sporadic CRC. CRC in IBD patients did not show survival difference compared to matched-pair sporadic CRC patients without distant metastases after curative resection. Surveillance might be important for early detection of CRC in IBD patients.

Identification of Bronchoalveolar Lavage Components Applying Confocal Laser Endomicroscopy.

BACKGROUND In many studies, confocal laser endomicroscopy (CLE) has proven to be a useful tool in pulmonology; nevertheless, the application in this field is still experimental. By contrast, CLE is almost a standard technique in gastroenterology. The aim of the present study was to demonstrate the identification of bronchoalveolar lavage (BAL) components applying CLE, using a dye. MATERIAL AND METHODS In 21 patients with various underlying diseases a bronchoscopy with BAL was performed. As in routine clinical practice common, BAL fluid (BALF) was analyzed in terms of cytologic, virologic, and microbiologic aspects. To one fraction of BALF, we added acriflavine. After centrifugation CLE was applied and the video sequences were analyzed by an experienced investigator. RESULTS Using CLE, BALF components (such as alveolar macrophages or leucocytes) could be easily identified. A further subdivision of leucocytes (neutrophilic, eosinophilic granulocytes, and lymphocytes) was not possible. Analogous to conventional cytology, a precise distinction of lymphocyte subpopulation (cd 4/cd 8 ratio) was not feasible. In terms of quantification, this is still the application field of flow cytometry and immunohistochemistry. CONCLUSIONS Using CLE, alveolar macrophages and leucocytes in stained BALF can be differentiated independent of smoking status. Further studies should be initiated in order to subclassify leucocytes in eosinophilic, neutrophilic granulocytes, and lymphocytes, which is important for routine clinical practice.

Confocal Laser Endomicroscopy for Diagnosing Malignant Pleural Effusions.

BACKGROUND Confocal laser endomicroscopy (CLE) enables "in vivo" microscopic tissue diagnosis based on tissue reflectance or tissue fluorescence upon application of fluorescence agents. The aim of the present study was to evaluate CLE as a new diagnostic approach for differentiation between malignant versus non-malignant pleural effusions. MATERIAL AND METHODS In 100 patients with pleural effusions, thoracentesis was performed. Cresyl violet and acriflavine were used as contrast agents for probe-based CLE of effusions. CLE video sequences were assessed by 4 independent investigators (2 experienced in this technique, 2 with only basic knowledge). In addition, all CLE samples were evaluated by an expert pathologist (p). Results were compared with conventional cytology of effusions and histology of cell blocks. RESULTS CLE reliably permitted identification of malignant cells in pleural effusions. Sensitivity for detection of malignant effusions was 87% (p: 87%) and 81% (p: 72%) for acriflavine and cresyl violet, respectively. With regard to specificity, acriflavine and cresyl violet yielded a mean value of 99% (p: 100%) and 92% (p: 100%). CONCLUSIONS In this pilot study, CLE permitted simple and rapid detection of malignant pleural effusions. Larger prospective studies are warranted to corroborate our findings.

Physiological intermolecular modification spectroscopy for the prediction of response to anti-tumor necrosis factor therapy in patients with inflammatory bowel diseases.

BACKGROUND/AIMS: Anti-tumor necrosis factor (TNF) antibodies have clinical efficiency only in a subgroup of patients with inflammatory bowel diseases (IBD). Prediction of clinical response is a critical clinical problem. Physiological intermolecular modification spectroscopy (PIMS) is a label-free technology performed in physiological conditions. PIMS enables real-time monitoring of dynamic molecular resonance of entire proteins and macromolecules of an individual. The aim of this study was to explore the capacity of PIMS to discriminate IBD patients regarding response to anti-TNF treatment. METHODS: Protein extracts of peripheral blood mononuclear cells (PBMC) from 30 outpatients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) and treated with infliximab were subjected to PIMS analysis in a blinded transversal study. Total protein from each patient's PBMCs was challenged with infliximab. Dynamic changes in macromolecular interaction were registered while the temperature rose from -37 to 37°C. Individual macromolecular volume and molecular elasticity were determined for each patient. RESULTS: Clinical data revealed that 67% of UC and 79% of CD patients responded to infliximab therapy during the 3-month study period based on their respective clinical activity score. These results confirm that PIMS data predicted response to anti-TNF therapy with an accuracy of 96%. CONCLUSION: PIMS stratified IBD patients into two groups, responders and nonresponders, which correlated with the clinical efficacy of anti-TNF therapy. PIMS seems to be a powerful technology to adapt IBD treatment to the individual patient. Further studies with PIMS might enable to predict clinical response to biological treatment in IBD patients before the therapy is initiated.

Effects of Adjuvant Exercise and Nutrition Therapy on Muscle Fibre Biomechanics in Gastrointestinal Cancer Patients.

Patients with aggressive cancer, e.g., gastrointestinal cancer, are prone (≥50% chance) to developing cancer cachexia (CC). Little is known about the effects of CC on the biomechanical function of muscle. A promising prevention strategy was found in the form of a multi-modal therapy combining mild resistance exercise (e.g., whole-body electro-myostimulation, WB-EMS) and a protein-rich diet. In a previous study of ours, this was effective in counteracting the loss of muscle mass, yet a systematic and comprehensive assessment of active and passive single muscle fibre functions was so far absent. This pilot study investigated the biomechanical function of single muscle fibres (rectus abdominis) from the biopsies of conventionally treated (pre-)cachectic cancer ((pre-)CC) patients (m = 9), those receiving the multi-modal therapy comprising WB-EMS training and protein-rich nutrition (m = 3), and a control group (m = 5). Our findings not only align with previous findings showing the absolute force loss in CC that is accelerated by atrophy but also speak in favour of a different, potentially energy- and Ca2+-homeostasis-related effect that compromises muscle contraction (F ~0.9 mN vs. F ~0.6 mN in control patients). However, myofibrillar Ca2+ sensitivity and the quality of contraction were unaltered (pCa50: 5.6-5.8). Single fibres from the (pre-)CC patients receiving WB-EMS training and protein supplementation were significantly more compliant (p < 0.001 at ≥130% of resting length L0). Those fibres displayed a similar softness to the ones from the control patients (axial compliance ~15 m/N at ≥130% L0), while single fibres from the patients with (developing) cachexia were significantly stiffer (axial compliance ~7 m/N, p < 0.001 at ≥130% L0). Adjuvant multi-modal therapy (WB-EMS training and nutritional support) contributes to maintaining the axial compliance of single fibres and potentially improves the quality of life for patients at risk of developing CC.

Maximum Heart Rate- and Lactate Threshold-Based Low-Volume High-Intensity Interval Training Prescriptions Provide Similar Health Benefits in Metabolic Syndrome Patients.

Exercise is an integral part of metabolic syndrome (MetS) treatment. Recently, low-volume high-intensity interval training (LOW-HIIT) has emerged as a time-efficient approach to improving cardiometabolic health. Intensity prescriptions for LOW-HIIT are typically based on maximum heart rate (HRmax) percentages. However, HRmax determination requires maximal effort during exercise testing, which may not always be feasible/safe for MetS patients. This trial compared the effects of a 12-week LOW-HIIT program based on: (a) HRmax (HIIT-HR), or (b) submaximal lactate threshold (HIIT-LT), on cardiometabolic health and quality of life (QoL) in MetS patients. Seventy-five patients were randomized to HIIT-HR (5 × 1 min at 80-95% HRmax), HIIT-LT (5 × 1 min at 95-105% LT) groups, both performed twice weekly on cycle ergometers, or a control group (CON). All patients received nutritional weight loss consultation. All groups reduced their body weight (HIIT-HR: -3.9 kg, p < 0.001; HTT-LT: -5.6 kg, p < 0.001; CON: -2.6 kg, p = 0.003). The HIIT-HR and HIIT-LT groups similarly, improved their maximal oxygen uptake (+3.6 and +3.7 mL/kg/min, p < 0.001), glycohemoglobin (-0.2%, p = 0.005, and -0.3%, p < 0.001), homeostasis model assessment index (-1.3 units, p = 0.005, and -1.0 units, p = 0.014), MetS z-score (-1.9 and -2.5 units, p < 0.001) and QoL (+10 points, p = 0.029, and +11 points, p = 0.002), while the CON did not experience changes in these variables. We conclude that HIIT-LT is a viable alternative to HIIT-HR for patients who are not able/willing to undergo maximal exercise testing.

[Inflammatory bowel diseases - therapy update 2022]. / Chronisch-entzündliche Darmerkrankungen.

Growing insights into the underlying immunopathogenesis of inflammatory bowel diseases (IBD) have led to the advent of targeted therapies, which selectively target pivotal mediators of the inflammatory process. This has enabled us to define and achieve novel therapeutic outcomes to prevent disease-associated complications and halt the progressive course of disease. In addition to already available treatment options, the selective Janus kinase type 1 inhibitor filgotinib and the selective sphingosine-1-phosphate receptor modulator Ozanimod have recently been approved for the treatment of ulcerative colitis patients. Furthermore, positive phase 2/3 induction and maintenance trial results have been reported for representatives of the class of IL-23p19 inhibitors, which are expected to further increase our therapeutic possibilities. All these agents can be applied as first-line or also subsequent treatment options and recent head-to-head trials have helped us to position these substances in our therapeutic algorithm. Nevertheless, there is still the currently unmet clinical need do establish predictive markers of response to identify the subgroup of IBD patients, that have a heightened probability of response to each therapy. In the following, we will give an overview of the recently approved or in late-stage clinical development tested substances and discuss their positioning in our therapeutic armamentarium.

Transabdominal ultrasonography for confirmation of accurate percutaneous endoscopic gastrostomy tube placement: analysis of patient- and procedure-related complications.

AIMS: Technique-related factors, patient-related factors, and localization determine the risk for complications in percutaneous endoscopic gastrostomy (PEG) tube placement. The objective of this study was to identify patient characteristics and ultrasonographic parameters after PEG tube placement concerning localization, which correlate with complications. MATERIAL AND METHODS: Patients undergoing PEG-tube placement were examined by abdominal ultrasound after dismissal from the endoscopic recovery room. Patient demographics, PEG characteristics, ultrasonographic parameters and complications were retrospectively analyzed. RESULTS: Of 64 enrolled patients, 59.4% were male and the mean age was 62.3 years. A significant negative correlation between complications at PEG placement and Body-Mass-Index (BMI; kg/m2) was observed (Spearman's Rho: -0.382; p=0.002). A low BMI <18 tended to be more frequent in the group with complication-related PEG removal compared to patients without (18.2% vs. 1.9%). Further descriptive analysis revealed that 4 patients (36.4% of N=11) with and 5 patients (9.4% of N=53) without PEG removal due to complications already had complications at the time of PEG placement. Of the patients with complications during follow-up, those with a peritoneal course (N=10) in ultrasound tended to have a lower BMI (mean ± standard deviation: 22.5±6.5 vs. 26.8±5.9) compared to those without (N=5). In all 4 patients with a triad of follow-up complications, peritoneal course, and complications at PEG placement, the tube was removed due to complications. CONCLUSIONS: Post-PEG-placement ultrasonography can help to determine complications in specific procedure-related conditions. A low BMI was found to be a relevant predictor of PEG-related complications, substantiating the need for early intervention in potentially PEG-relevant indications.

Real Life Study of Lenvatinib Therapy for Hepatocellular Carcinoma: RELEVANT Study.

Introduction: In the REFLECT trial, lenvatinib was found to be noninferior compared to sorafenib in terms of overall survival. Here, we analyze the effects of lenvatinib in the real-life experience of several centers across the world and identify clinical factors that could be significantly associated with survival outcomes. Methods: The study population was derived from retrospectively collected data of HCC patients treated with lenvatinib. The overall cohort included western and eastern populations from 23 center in five countries. Results: We included 1,325 patients with HCC and treated with lenvatinib in our analysis. Median OS was 16.1 months. Overall response rate was 38.5%. Multivariate analysis for OS highlighted that HBsAg positive, NLR >3, and AST >38 were independently associated with poor prognosis in all models. Conversely, NAFLD/NASH-related etiology was independently associated with good prognosis. Median progression-free survival was 6.3 months. Multivariate analysis for progression-free survival revealed that NAFLD/NASH, BCLC, NLR, and AST were independent prognostic factors for progression-free survival. A proportion of 75.2% of patients suffered from at least one adverse effect during the study period. Multivariate analysis exhibited the appearance of decreased appetite grade ≥2 versus grade 0-1 as an independent prognostic factor for worse progression-free survival. 924 patients of 1,325 progressed during lenvatinib (69.7%), and 827 of them had a follow-up over 2 months from the beginning of second-line treatment. From first-line therapy, the longest median OS was obtained with the sequence lenvatinib and immunotherapy (47.0 months), followed by TACE (24.7 months), ramucirumab (21.2 months), sorafenib (15.7 months), regorafenib (12.7 months), and best supportive care (10.8 months). Conclusions: Our study confirms in a large and global population of patients with advanced HCC, not candidates for locoregional treatment the OS reported in the registration study and a high response rate with lenvatinib.

Leptin, obestatin and apelin levels in patients with obstructive sleep apnoea syndrome.

BACKGROUND: Recent studies suggest that adipose tissue hormones are involved in the pathogenesis of obstructive sleep apnoea syndrome (OSAS). The role of leptin, obestatin and apelin still needs to be established. MATERIAL/METHODS: Ten patients with newly diagnosed OSAS (AHI >10/h and ESS >10 points) were enrolled in the study as well as ten healthy volunteers as controls. All underwent measurements for Leptin, Obestatin and Apelin in four hour intervals during diagnostic polysomnography for 24 h and the patients also three months after onset of CPAP treatment. Furthermore the HOMA-index and body composition were quantified. RESULTS: Plasma apelin levels in the patients decreased under CPAP therapy, but showed no significant difference in patients and volunteers. We found a positive correlation to AHI, BMI in the therapy group at all observation points. Leptin plasma levels were higher in the patient group and decreased after onset of CPAP therapy. Leptin plasma levels were positively correlated to the BMI, min. 02 and AHI in the patient group before therapy. Plasma obestatin levels did not differ significantly in these three observation groups, but were partly correlated to AHI and weight in the newly diagnosed OSAS group. CONCLUSIONS: In agreement with previous investigations, we could demonstrate a difference in leptin plasma levels between healthy volunteers and patients with newly diagnosed OSAS. Apelin decreases under CPAP therapy, but not significantly. Obestatin remains unchanged after onset of CPAP. We further found a linkage between leptin plasma levels and BMI, AHI and weight in the untreated patient group.

Viral FLIP blocks Caspase-8 driven apoptosis in the gut in vivo.

A strict cell death control in the intestinal epithelium is indispensable to maintain barrier integrity and homeostasis. In order to achieve a balance between cell proliferation and cell death, a tight regulation of Caspase-8, which is a key player in controlling apoptosis, is required. Caspase-8 activity is regulated by cellular FLIP proteins. These proteins are expressed in different isoforms (cFLIPlong and cFLIPshort) which determine cell death and survival. Interestingly, several viruses encode FLIP proteins, homologous to cFLIPshort, which are described to regulate Caspase-8 and the host cell death machinery. In the current study a mouse model was generated to show the impact of viral FLIP (vFLIP) from Kaposi's Sarcoma-associated Herpesvirus (KSHV)/ Human Herpesvirus-8 (HHV-8) on cell death regulation in the gut. Our results demonstrate that expression of vFlip in intestinal epithelial cells suppressed cFlip expression, but protected mice from lethality, tissue damage and excessive apoptotic cell death induced by genetic cFlip deletion. Finally, our model shows that vFlip expression decreases cFlip mediated Caspase-8 activation in intestinal epithelial cells. In conclusion, our data suggests that viral FLIP neutralizes and compensates for cellular FLIP, efficiently counteracting host cell death induction and facilitating further propagation in the host organism.

A Novel Mobile Phone App (OncoFood) to Record and Optimize the Dietary Behavior of Oncologic Patients: Pilot Study.

BACKGROUND: Catabolism and tumor-specific therapy lead to reduced nutrient intake and weight loss in cancer patients. Maintaining a specific individualized diet can be challenging for the patient as the nutritional counseling options are limited. Monitoring of nutrient intake and frequent feedback are, however, vital for successful nutritional therapy because they support the patient's compliance and realization of dietary therapeutic goals. OBJECTIVE: This study aimed at investigating the feasibility and applicability of a novel mobile phone app to assess and evaluate dietary behaviors in oncologic patients. METHODS: To determine dietary habits and food preferences in oncologic patients, initially 1400 nutritional records were evaluated and analyzed. The results provided the basis for creating a nutritional mobile phone app. Key requirements for the app included simple handling, recording the daily intake, and a comparison of nutrient targets and current status. In total, 39 cancer patients were recruited for the study; 15 patients dropped out prior to the study. All patients received a nutritional anamnesis, nutritional analysis, and nutritional counseling. Individual energy and nutrient aims were defined. The intervention group (n=12) additionally used the app. Weight and body composition of each group were evaluated after 4 weeks. RESULTS: The app group gained significantly more weight (P=.045; mean weight 1.03 kg vs -1.46 kg). Also, skeletal muscle mass showed a significant increase in the app group (P=.009; mean skeletal muscle mass 0.58 kg vs -0.61 kg) compared with the control group. There was no significant difference between groups relating to the daily protein intake (P=.06). Additionally, there was a decrease in macronutrient intake during the study period in the control group. CONCLUSIONS: Our study indicates that patients who track their daily dietary habits using a mobile phone app are more likely to reach their nutritional goals than the control patients. Further large-scale studies are needed to confirm these initial findings and test the applicability on a broader basis.

Clinical efficacy of the Toll-like receptor 9 agonist cobitolimod using patient-reported-outcomes defined clinical endpoints in patients with ulcerative colitis.

BACKGROUND: The Toll-like-receptor 9 (TLR-9) agonist cobitolimod (DIMS0150, Kappaproct®) is a promising therapeutic option for ulcerative colitis (UC) patients. AIMS: The objectives of this post-hoc analysis using the COLLECT study data was to investigate the clinical effects of cobitolimod using patient-reported-outcomes (PRO) defined endpoints. METHODS: Dual topical administration of cobitolimod was studied in a randomised, multicentre clinical trial named COLLECT in moderate-to-severe UC patients. Symptomatic remission (SR) was studied in 104 patients based on their e-diary records and was defined as absence of blood in stool and a mean daily stool frequency (SF) < 4. RESULTS: SR was achieved at week 4 in 17.1% of cobitolimod vs. 5.9% of placebo treated patients (p = 0.13), at week 8 in 35.7% vs. 17.6% (p = 0.07), and at week 12 in 38.6% vs. 17.6% (p = 0.04) of the patients, respectively. SR rates with cobitolimod and placebo in anti-TNFα experienced patients were smaller but with a broadly similar relative effect-size to anti-TNFα naïve patients. Clinical efficacy was higher in patients with moderate compared to severe disease. CONCLUSIONS: Application of the Toll-like-receptor 9 (TLR-9) agonist cobitolimod is able to induce remission as assessed by PRO measures in UC patients with moderate-to-severe activity as well as in anti-TNFα experienced and naïve patients supporting the overall efficacy of the substance.

The impact of hospitalization on the performance of capsule endoscopy (CE).

BACKGROUND: For proper evaluation of capsule endoscopy (CE), a complete examination is necessary. AIM: We evaluated risk factors of an incomplete CE with focus on patient hospitalization. METHODS: We retrospectively evaluated 161 consecutive patients who underwent CE between 01.07.2013 and 13.03.2016. Main indications were active bleeding, iron deficiency anemia (IDA), inflammatory bowel disease (IBD), abdominal pain, and familial adenomatous polyposis (FAP). RESULTS: We report the results of 103 in-patients and 56 out-patients. Eighty-two patients were male, average age was 58.9 years (range 18-90). Indications for CE were active bleeding (103 patients), IDA and IBD (16 patients), and FAP, abdominal pain and others (eight examinations each). All FAP patients were out-patients, but showed the longest small bowel transit time (SBTT) of 443.6min (p=0.0001). The shortest SBTT was found in out-patients without FAP (267.5min, p<0.05). In the in-patient group, nine endoscopies did not record the entire small bowel (8.7%) due to battery depletion, compared with only one incomplete examination in the out-patients (1.8%, p=0.036). We found pathologic lesions in the last 30min of the SBTT in 43 patients, and this indicates the necessity for complete examination. Thirteen of these 43 patients showed major lesions such as ulcers or angiodysplasia in this last region alone. CONCLUSION: In-patients might require special treatment to ensure complete examination, since a considerable amount of pathologies can only be found in the ileum.

Weekly High-dose 5-Fluorouracil as 24-hour Infusion Combined with Sodium Folinic Acid (AIO regimen) Plus Irinotecan in Second-line and Sequential Therapy of Metastatic Colorectal Cancer (CRC).

BACKGROUND/AIM: The aim of this work was to evaluate the efficacy and safety of second-line treatment with weekly high-dose 5-fluorouracil (5-FU) as a 24-hour infusion (24-h inf.) combined with sodium folinic acid (FA) (AIO-regimen) plus irinotecan (Iri.) after pretreatment with AIO-regimen plus oxaliplatin (L-OHP). PATIENTS AND METHODS: Patients with non-resectable distant CRC metastases were enrolled in a prospective phase II study for palliative second-line treatment after previous progression of first-line treatment in accordance with the AIO-regimen plus oxaliplatin. On an outpatient basis, the patients received a treatment regimen comprising of weekly 80 mg/m2 irinotecan in the form of a 1-hour i.v. infusion and 2,000 mg/m2 5-FU combined with 500 mg/m2 sodium folinic acid administered as a 24-h infusion i.v. once weekly. RESULTS: During second-line treatment, a total of 59 patients received 520 chemotherapy applications. As the main higher-grade symptom of toxicity, diarrhea (NCI-CTC-toxicity grade 3) presented in 8 patients (13.6%, 95%CI=5.1-23.7), followed by leukocytopenia (CTC grade 3) in 3 patients (5.1%, 95%CI=0-11.9), followed by thrombocytopenia (CTC grade 3) in 1 patient (1.7%, 95%CI=0-5.1). Fifty-nine patients were evaluable for treatment response. The remission data can be summarized as follows: complete remission (CR); n=0; partial remission (PR); n=6 (10%; 95%CI=3.4-18.6); stable disease (SD); n=31 (53%; 95%CI=39.0-64.4); progressive disease (PD); n=19 (33%; 95%CI=20.3-44.1). The median progression-free survival (PFS) rate (n=59) was 4.2 months (range=3.8-5.8 months). The median survival time counted from the start of second-line treatment (n=59) 14.2 months (range 8.2-17.3 months) and the median survival time counted from the start of first-line therapy (n=59) 25 months (range 19-27 months). CONCLUSION: Palliative second-line treatment according to the AIO regimen plus irinotecan offers both a favourable toxicity profile and promising efficacy in second-line and palliative sequential therapy.

[Novel therapeutic approaches in inflammatory bowel diseases]. / Neues zur Therapie der chronisch-entzündlichen Darmerkrankungen.

Increasing knowledge regarding the immunopathogenesis of IBD has led to the development or approval of novel therapeutic agents for the treatment of Crohn's disease or ulcerative colitis. The new substances for example include antibodies against IL-12 / 23, anti-adhesion molecules and antisense oligonucleotides. The increase of therapeutic options will lead to a change of currently used therapeutic algorithms. Biomarkers to ensure a more individualized therapeutic approach are urgently needed to improve an efficient therapy of IBD patients.

The Offer of Advanced Imaging Techniques Leads to Higher Acceptance Rates for Screening Colonoscopy - a Prospective Study.

BACKGROUND: Colonoscopy plays a fundamental role in early diagnosis and management of colorectal cancer and requires public and professional acceptance to ensure the ongoing success of screening programs. The aim of the study was to prospectively assess whether patient acceptance rates to undergo screening colonoscopy could be improved by the offer of advanced imaging techniques. MATERIALS AND METHODS: Overall, 372 randomly selected patients were prospectively included. A standardized questionnaire was developed that inquired of the patients their knowledge regarding advanced imaging techniques. Second, several media campaigns and information events were organized reporting about advanced imaging techniques, followed by repeated evaluation. After one year the evaluation ended. RESULTS: At baseline, 64% of the patients declared that they had no knowledge about new endoscopic methods. After twelve months the overall grade of information increased significantly from 14% at baseline to 34%. The percentage of patients who decided to undergo colonoscopy because of the offer of new imaging methods also increased significantly from 12% at baseline to 42% after 12 months. CONCLUSIONS: Patients were highly interested in the offer of advanced imaging techniques. Knowledge about these techniques could relatively easy be provided using local media campaigns. The offer of advanced imaging techniques leads to higher acceptance rates for screening colonoscopies.

[Update: chronic inflammatory bowel disease]. / Update: chronisch entzündliche Darmerkrankungen.

Crohn's disease and ulcerative colitis are the major entities of inflammatory bowel diseases (IBD). IBD is a clinical diagnosis, which is supported by endoscopic, histologic, radiologic, sonographic and laboratory findings. IBD are not restricted to the GI-tract but are instead systemic diseases that often involve extra-intestinal manifestations. Aim of the rational medical therapy is the induction and maintenance of a steroid-free remission. The medical therapy depends on the severity, activity and extent of disease as well as the disease course of the patient. There is the dire necessity for an individualized therapeutic concept as the natural disease course differs between the patients.