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Background: Idiopathic and secondary megacolon (MC) and megarectum (MR) in adults is associated with persistent bowel dilatation and reduced intestinal motility. Little is known about the optimal treatment of this rare disease. Therefore, we retrospectively analysed long-term data from these patients in 5 community and university hospitals, focusing on conservative versus surgical treatment., Methods: Patient records from 7/2004 to 9/2021 were screened for colorectal diseases with severe constipation and persistent megacolon ≥ 9.0 cm and/or megarectum ≥ 6.5 cm. Follow up-data was collected through telephone interviews and written surveys. ClinicalTrialsgov NCT04340856., Results: Sixty-seven patients with idiopathic (n=10) and secondary (n=57) MC or MR were identified with only 20 of 67 patients (29.9%) correctly diagnosed. Mean/median age was 64/69 (range 18-93) years. Thirty-two patients were treated with laxative regimens, and 35 underwent surgery (colostomy: n=12, segmental resection, or hemicolectomy: n=10, (sub)total colectomy: n= 13) after conservative treatment attempts in 32/35 (91.4%). The mean/median follow-up was 4.2/2.7 (range 0.1-17.0) years. The readmission rate for MC-associated symptoms was significantly higher after conservative treatment than after surgical therapy at 12 (0.84 vs. 0.36 per patient, p=0.036), 24 (1.00 vs. 0.52, p=0.048) and 36 (1.13 vs. 0.58, p=0.047) months, as was the number of patients with persistent laxative dependence (28/32 (87.5%) vs. 19/33 (57.6%); p = 0.007). Therapy-associated adverse events (Clavien-Dindo classification) were documented more often in surgically treated patients (11/35, 31.4%) (p=0.025)., Conclusion: Surgical treatment may be considered earlier if idiopathic or secondary MC or MR is correctly diagnosed, and conservative treatment has been attempted., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Hepatocellular carcinoma (HCC) is the sixth most common neoplasia and the third leading cause of cancer-associated deaths worldwide. Most cases arise in patients with cirrhosis, and early detection through periodic screening can make it potentially curable. The presence of extrahepatic metastases (EHM) affects treatment decisions and curability. The lungs are the most common site for EHM, followed by lymph nodes, bones, and the adrenal glands. Interestingly, approximately only 15 cases of HCC metastasizing to the pituitary gland have been reported so far.The most common symptoms of pituitary metastasis (PM) arising from HCC are nerve palsies affecting the third, fourth, and sixth cranial nerves. Other symptoms, such as diabetes insipidus or pituitary insufficiencies, are present in a minority of cases. Detecting PM is difficult given its rarity. Gold-standard treatments for these patients have not yet been established, but the prognosis is dismal, with a median overall survival of only 4.5 months. In this paper, we present an interesting case of PM as the first symptom of an HCC in a 75-year-old female. We also present an overview of all cases reported to date with emphasis on symptom presentation and survival after diagnosis.Given the improvement of systemic therapy, more cases are diagnosed in both oligometastatic and palliative conditions. Therefore, better approaches and treatment modalities for extrahepatic metastases due to HCC should be defined., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

Budd-Chiari syndrome is a rare vascular disorder characterized by obstruction of the hepatic venous outflow. Various diseases causing coagulopathy play a role in aetiology, such as myeloproliferative disorders. Acute vascular occlusion may lead to acute phlebitis with fever. The classic triad of acute liver failure may be present with ascites, hepatomegaly, and abdominal pain. However, subacute courses of disease were also observed. Because of the variable symptoms and severity extent, depending on the acuity of the course and the extent of the affected vessels, diagnosis is often difficult. Sonography, as a ubiquitously available and cost-effective diagnostic tool, plays a leading role. Doppler ultrasonography can be used to visualize hemodynamics in particular. In acute thrombotic occlusion, the affected hepatic veins usually cannot or only partially be visualized. In non-occluding thrombi, turbulent flow patterns may develop in the area of venous outflow obstruction, and flow velocity is then increased in the area of stenosis. Contrast enhanced ultrasound offers even better specificity of diagnosis. Computed tomography and magnetic resonance imaging can directly visualize thrombi and the cause of obstruction. Once the diagnosis is confirmed, anticoagulation must be initiated, but therapy of the underlying disease must also be started. If symptom-controlling measures are not sufficient, angioplasty/stenting to reopen short-segment stenoses or implantation of a TIPSS device may be considered. Liver transplantation remains ultima ratio. As studies on the precision of diagnostic methods are controversial, the characteristics of imaging for BCS are therefore summarized in this review on the basis of several illustrating case reports., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Throughout the past decades, considerable progress has been made in the (early) diagnosis and treatment of gastrointestinal cancers. However, the prognosis for advanced stages of gastrointestinal tumors remains limited for many patients and approximately one third of all tumor patients die as a result of gastrointestinal tumors. The prevention and early detection of gastrointestinal tumors is therefore of great importance.For this reason, we summarize the current state of knowledge and recommendations for the primary, secondary and tertiary prevention of esophageal, stomach, pancreas, liver and colorectal cancer in the following., Competing Interests: Bzgl. Nukleosid/Nukleotid-Analoga zur Behandlung der chronischen Hepatitis B: AT erhielt Beratungs- und Vortragshonorare sowie Forschungsförderung der Firma Gilead., (Thieme. All rights reserved.)

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

In recent years, immune checkpoint inhibitors (ICIs) were successfully introduced to cancer therapy, and these drugs have already become essential for the treatment of various noncurable tumors. However, monotherapy in advanced hepatocellular carcinoma (aHCC) failed to show statistically significant improvement.Recently, the combination of atezolizumab and bevacizumab demonstrated efficacy of combining ICI and VEGF inhibition, further substantiating previous data on synergistic mechanisms among respective substance classes.As TKI treatment is currently standard of care for aHCC, and ICIs are approved by the FDA and available in many areas of the world, numerous patients may have been treated with monotherapy of those drugs. However, it remains unclear if failure to monotherapy has an impact on combination therapy. We therefore report a patient well responding to combination therapy despite previous failures to TKI and ICI monotherapy., Competing Interests: Andreas Teufel received fees, travel expenses or project grants from the following companies: IPSEN, Roche, Lilly, Bayer, Esai., (© Georg Thieme Verlag KG Stuttgart · New York.)

Older patients (65 years and over) represent the majority of patients with a cancer diagnosis. For oesophageal carcinomas, the age peak is in the seventh to eighth decade of life. In gastric carcinoma, 1/3 of patients are older than 75 years and approximately 45 % of colon carcinoma patients are ≥ 75 years old.Due to existing comorbidities, age-related changes and polypharmacy, older patients present a special challenge in tumor therapy.In studies, these patients are usually clearly under-represented and "elderly"-studies are rare.New surgical procedures with laparoscopy and also robotic provide advantages for esophageal and gastric carcinoma, which in the future can reduce postoperative morbidity in relation to cardiac and pulmonary complications for old and older patients. The selection of suitable patients is essential here.With regard to chemotherapy, fluoropyrimidines and oxaliplatin are well tolerated; triplet therapies should be avoided. Immunotherapy in particular offers an interesting alternative to standard chemotherapy due to its better side effect profile., Competing Interests: Prof. Dr. med. M. Ebert erklärt einen Interessenkonflikt als Leiter einer klinischen Studie, welche durch BMS unterstützt wird., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background and Aim:  The role of therapeutic drug monitoring (TDM) in ustekinumab (UST) therapy for Crohn's disease (CD) has not been established, as only few studies have analyzed the relationship between UST serum concentrations and clinical outcome. In this pilot study, we retrospectively examined the potential of UST-concentrations (cUST) 8 weeks after induction (cUSTw8) to predict clinical response at week 16., Methods:  Serum samples and clinical data from patients (n = 72) with moderate to severely active CD who received intravenous induction with UST were retrospectively analyzed. cUST were quantitated using liquid chromatography-tandem mass spectrometry (LC-MSMS). A receiver-operating characteristic (ROC) curve and area under ROC curve (AUROC) was computed to analyze the predictive potential of cUSTw8 for clinical response at week 16 and to determine the minimal therapeutic UST trough concentration., Results:  Forty-four patients (61 %) achieved clinical response to UST therapy at week 16. cUSTw8 was moderately effective to predict clinical response with a minimal therapeutic cUSTw8 of 2.0 mg/l (AUC 0.72, p = 0.001)., Conclusion:  Trough concentrations of UST 8 weeks after induction predict clinical response to therapy in week 16 with moderate sensitivity and specificity. TDM using LC-MSMS could prove beneficial in personalized UST therapy of patients with CD by identifying individuals with subtherapeutic concentrations who might benefit from dose escalation., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht.The authors report no conflict of interest related to this work. Outside of this project, the authors report the following disclosures:AKT: Speakers honorary or travel support from Abbvie, MSD and TakedaAMG: Travel support from Abbvie and JanssenPHo: Speakers honorary and travel support from JanssenTK: Speakers honorary and/or consultant fees from AbbVie, Janssen, MSD, Novartis, Takeda and PfizerJW: Speakers honorary and/or consultant fees from AbbVie, Ardeypharm, Ferring, Janssen, MSD, Novartis, Pfizer, Roche and TakedaAG: Speakers honorary, travel support and/or consultant fees from Abbvie, Amgen, Janssen, MSD, Pfizer, Takeda and TillotsPHa: Speakers honorary, travel support and/or consultant fees from Abbvie, Falk, Janssen, MSD and TakedaJK: Speakers honorary, travel support and/or consultant fees from Abbvie, BMS, Celltrion, Falk, Janssen, MSD, Pharmacosmos, Shield, Takeda, Tillots and ViforWR: Speakers honorary and/or consultant fees from Abbvie, Janssen and TakedaLAS, TI, AT, RS, NS and MPE report no disclosures or conflicts of interest for this project, (© Georg Thieme Verlag KG Stuttgart · New York.)

Objectives:  Antibiotic prophylaxis in patients with liver cirrhosis and upper gastrointestinal bleeding significantly reduces the risk of concomitant bacterial infections and early mortality. The goal of our study was to determine the current status of antibiotic prophylaxis in departments of gastroenterology in Germany., Methods:  Representatives of gastroenterology departments were asked to provide data about indication for, and duration of, antibiotic prophylaxis and choice of antibiotic in esophageal varices bleeding in patients with liver cirrhosis., Results:  326 of 779 contacted departments of gastroenterology participated in the study. Whereas antibiotic prophylaxis is used in 98.5 % (n = 321/326) of cases, it is used only in 7.1 % (n = 23/322) depending on the Child-Pugh-Score. In 19.4 % (n = 62/320), a prophylaxis is given even to patients with an elective banding of esophageal varices without bleeding. Third generation cephalosporins are used most frequently (66.5 %; n = 248/373) followed by fluoroquinolones (19.9 %; n = 74/373). The duration of prophylaxis was 3 days in most cases (32.3 %; n = 104/322), 1 day in 9.3 % (n = 30/322) and 7 days as recommended by German treatment guidelines in 24.8 % (n = 80/322). A standard of procedure (SOP) for antibiotic prophylaxis in esophageal varices bleeding is available in 45.1 % (n = 147/326)., Conclusion:  Our study shows that the applied standards for antibiotic prophylaxis in esophageal varices bleeding varies greatly in Germany. Future studies about the necessary duration of prophylaxis and its dependency from the Child-Pugh-Score are needed so that unnecessary antibiotic prescriptions can be avoided. The avoidance of antibiotic prophylaxis in elective banding of non-bleeding esophageal varices, which is not recommended by guidelines and was used by about 20 % of participants in our study, can already reduce antibiotic use., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background and Aim:  Colorectal cancer (CRC) screening can effectively reduce cancer-associated mortality. In Germany, individuals over the age of 50 or 55 have access to CRC screening services. However, utilization rates are persistently low, particular in the male population. This observational study investigates the effect of standard versus gender-specific invitation letters on utilization of CRC screening services., Methods:  We analyzed utilization rates of individuals who were insured by a large health insurance fund in Bavaria, Germany. Persons who became eligible for CRC screening received a standard (2013-2014) or a gender-specific invitation letter (2015-2016). We compared utilization rates within 6 months after receipt of the invitation letter using billing codes of the health insurance fund., Results:  Invitation letters were sent to 49 535 individuals, of which 48.8 % were gender-specific. The overall utilization rate did not differ between recipients of the standard versus gender-specific invitation letter (11.6 % vs 11.1 %; RR: 0.97 [0.92-1.02], p = 0.19). However, uptake of screening colonoscopy was significantly higher among recipients of gender-specific invitations (2.9 % vs 3.5 %; RR: 1.21 [1.04-1.39], p = 0.01), whereas utilization of fecal occult blood tests declined (10.4 % vs 9.7 %; RR: 0.93 [0.88-0.99], p = 0.016)., Conclusions:  Gender-specific design of invitation letters can modify the patients' preference for specific CRC screening services and increase the acceptance of screening colonoscopy., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Hepatocellular carcinomas (HCC) that extend into the vena cava and the right atrium have a poor prognosis. Surgical approaches including partial hepatectomy and thrombectomy are the most frequently reported treatment options. However, most patients with advanced HCC are not eligible for complex surgical interventions due to reduced liver function, comorbidities, and metastases. At the same time, systemic treatment options of HCC have expanded in recent years. Here, we report 3 cases of patients with advanced HCC who developed a cavoatrial tumor thrombus (CATT) after initial surgical or interventional therapy. The patients were consequently treated with sorafenib or nivolumab. In all cases, the tumor responded to systemic treatment with disease stabilization or partial regression. Overall survival after diagnosis of CATT was 3 and 17 months for sorafenib and 7 + months for nivolumab. Compared to survival rates of alternative treatment options, systemic therapies demonstrated comparable outcomes. In summary, pharmacotherapy is an efficient and well worth option to treat patients with HCC and CATT and should be an integral part of a multimodal therapy concept., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objectives:  The M-ANNHEIM classification of chronic pancreatitis (CP) stratifies degrees of disease severity according to the M-ANNHEIM-Severity-Score. We aimed to demonstrate the clinical usefulness of the M-ANNHEIM-Severity-Score in quantifying and predicting the frequency of pancreatic surgery, and to establish the M-ANNHEIM-Surgery-Score as a simplified system for patient surveillance regarding the demand of pancreatic surgery., Methods:  We performed a retrospective, cross-sectional study with 741 CP patients (Mannheim/Germany, n = 537; Gießen/Germany, n = 100; Donetsk/Ukraine, n = 104) categorized according to the M-ANNHEIM classification., Results:  We observed a significantly higher M-ANNHEIM-Severity-Score in patients that were classified within 7 days preceding pancreatic surgery than in individuals that did not require surgery (p < 0.001, Mann-Whitney-U-test). Using a logistic regression analysis with all variables of the M-ANNHEIM-Severity-Score, we established the M-ANNHEIM-Surgery-Score as a simplified new tool to identify patients that may require surgery. A receiver operating characteristic-analysis revealed a cut-off-value of 9 points within the M-ANNHEIM-Surgery-Score to identify these individuals (sensitivity 78.7 %, specificity 91 %). Based on the M-ANNHEIM-Surgery-Score, we defined three categories for demand of surgery with frequencies of pancreatic operations of 1.6 % (n = 7/440) in the "Baseline-Demand"-category, 7 % (n = 12/172) in the "Low-Demand"-category (p < 0.0001, Chi-square-test, OR 4.6, Confidence Interval (CI) 1.8 - 12), and 54 % (n = 70/129) in the "High-Demand"-category (p < 0.0001, OR 73, CI 32 - 167). Patients that were categorized for the "High-Demand"-category, but were not operated on, had a significantly increased ratio of clinical features that hamper performance of surgery (p < 0.001, Chi-square-test)., Conclusions:  The M-ANNHEIM-Surgery-Score represents a useful tool to monitor patients with CP and to estimate the demand of surgery in CP., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objectives: Patients with inflammatory bowel disease (IBD) frequently reveal features of pancreatic inflammation. However, the prevalence of IBD in patients with alcoholic pancreatitis (AP) and nonalcoholic pancreatitis (NAP) has not yet been determined, and the prevalence of IBD in patients with autoimmune pancreatitis (AiP) from Germany is unknown., Aims: Thus, we aimed, first, to determine the prevalence of IBD in AP, NAP, and AiP from a tertiary center in Germany and, second, to characterize patients with AiP and IBD., Methods: We performed a retrospective cross-sectional study to determine the prevalence of IBD in patients with different forms of pancreatitis presenting to our clinic., Results: Compared to the general population and to a control group with viral hepatitis from our clinic, we observed the most significant increase of IBD in patients with AiP (n = 3/28; p < 0.0001 vs. general population, binomial proportion test; p = 0.0112 vs. hepatitis group, Fisher's exact test), followed by a significant increase in subjects with NAP (n = 11/278; p < 0.0001 vs. general population, binomial proportion test; p = 0.0338 vs. hepatitis group, Fisher's exact test). A review of previous studies on the prevalence of IBD among patients with AiP revealed a combined prevalence of 12 % (n = 43/355). Type 2 AiP is significantly more often associated with IBD than type 1 AiP (n = 28/48, 58 % vs. n = 7/129, 5 %; combined patient cohort, p < 10E - 12; Fisher's exact test)., Conclusions: Immune-mediated mechanisms related to IBD may participate in the development of AiP, especially AiP type 2, and may also increase the risk for the development of other forms of pancreatic inflammation., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background and Aim  Participation rates in the German colorectal cancer screening program are low. Starting in 2013, a large health insurance plan in Bavaria, Germany, is sending an additional invitation letter to insured individuals when they turn 50 or 55 years and become eligible for participation in the program. The letter provides detailed information on colorectal cancer screening. We assessed the impact of the invitation letter on utilization rates. Methods  Insurance claims data of a total of 48 343 individuals who had turned 50 or 55 years between 2012 to 2014 were reviewed for utilization rates of screening colonoscopy and fecal blood tests. Utilization rates 1 year prior (2012) and 2 years after introduction of the invitation letter (2013 and 2014) were compared. Furthermore, providers of colorectal cancer screening were determined. Results  Within 6 months after turning 50 or 55 years, 8.8 - 10.2 % of all insured individuals participated in colorectal cancer screening, with the majority being females. After the introduction of the invitation letter, a moderate increase in participation rates could be observed (increase to 109 % [RR 101.7 - 117.3 %, p = 0.02] in 2014). The uptake rate of screening colonoscopy was significantly higher in recipients of the letter (increase to 138.4 % [RR 110.4 - 173.8 %, p = 0.0043] in 2013 and to 149 % [RR 119.5 - 186.3 %, p = 0.0003] in 2014). Furthermore, a significantly higher proportion of general practitioners and gastroenterologists provided colorectal cancer screening in individuals receiving the invitation letter. Conclusions  Introduction of an invitation letter can improve participation rates for colorectal cancer screening., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Sorafenib, a receptor tyrosine kinase-inhibitor with anti-proliferative and anti-angiogenic activity, is currently the only approved systemic treatment for patients with hepatocellular carcinoma. It inhibits downstream signaling of VEGFR-2, PDGFR, c-Kit receptors and BRAF. Over the last four years comprehensive experience with sorafenib in this indication has been accumulated. In this review we discuss the current data on the use of sorafenib in patients with advanced HCC including special patient populations such as patients with impaired liver function, patients after transplantation, and others. The most frequent side-effects and practical tips on how to manage them are discussed in detail. In addition, we summarize the current experimental data on the use of sorafenib in combination treatment, e. g., together with transarterial chemoembolisation or other targeted agents., (© Georg Thieme Verlag KG Stuttgart · New York.)

As a consequence of recent studies the treatment of gastrointestinal cancers has become challenging and is undergoing constant changes on the basis of the results of new trials. The steering committee of the working group on gastrointestinal cancers of the Deutsche Gesellschaft für Verdauungs- und Stoffwechselkrankheiten has decided to summarise and present recent updates of the current treatment guidelines and recommendations for the most relevant gastrointestinal malignancies. In this review we have included recent findings from large trials on esophageal, gastric, pancreatic, cholangiocellular and liver cancers, as well as colorectal cancers, neuroendocrine tumours and lymphomas. This includes an update on the combination with novel targeted agents and the introduction of potential predictive biomarkers in the selection of the appropriate treatment strategy.

Tumours of the gastrointestinal tract are the single largest group of malignant tumours of humans accounting for approximately 2 million new cases and over 1.2 million deaths annually. They are most commonly a disease of the elderly, and their relative and absolute frequency will rise continuously due to an ageing population. This explains why the prevalence of gastric cancer increases in spite of a decreasing incidence. Gastrointestinal tumours will remain a major clinical and health economical challenge. The prognosis is often dismal. Most of these cancers are diagnosed in an advanced stage, which prohibits curative treatment and limits treatment options. In order to circumvent these problems, we need to develop strategies that allow identification of at-risk patients and tumours at an early stage, and raise the compliance in the general population for screening programmes. There is a great need in clinics for prognostic and predictive biomarkers that are able to tailor patient treatment at different stages of the disease.