Pancreatic cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up

The opportunity to detect pancreatic cancer (PC) when potentially curable depends on early diagnosis and an ability to identify and screen high-risk populations before symptoms arise. Identification of a high-risk population is challenging and optimal screening tools remain unclear.1 Older age is the strongest risk factor; incidence peaks at 65-69 years in males and 75-79 years in females.2 A pooled analysis of 117 meta-analyses assigned a relative risk to a number of common risk factors (Supplementary Table S1, available at https://doi.org/10.1016/j.annonc.2023.08.009).3 The vast majority (>80%) of PCs arise due to sporadically occurring somatic mutations. Only a small proportion are due to inherited deleterious germline mutations.1 Familial PC, defined as at least two first-degree relatives with PC, accounts for only 4%-10% of all cases. Variants in BRCA2 are the most common genetic abnormalities seen in familial PC. Other familial syndromes linked to PC are listed in Supplementary Table S2, available at https://doi.org/10.1016/j.annonc.2023.08.009. Individuals from families at risk should receive genetic counselling and be considered for enrolment in investigational screening registries. Currently, in high-risk individuals, annual endoscopic ultrasound (EUS) and/or pancreatic magnetic resonance imaging (MRI) are the procedures of choice for surveillance.4 Surveillance programmes usually begin at age 50 years (or 10 years earlier than the age of the youngest affected relative). Prospective surveillance data in high-risk individuals demonstrated high rates of resectability and encouraging observations of long-term survival.5, 6, 7, 8, 9 In sporadic PC, the major risk factors are tobacco, Helicobacter pylori infection and factors related to dietary habits (high red meat, high alcohol intake, low fruit and vegetable intake, overweight/obesity and type 2 diabetes mellitus).2,3,10 Chronic pancreatitis, irrespective of the cause (alcohol abuse, smoking, genetic mutations), is a risk factor for PC. A proportion of the risk factors associated with PC are potentially modifiable, affording a unique opportunity for primary prevention that is yet to be realised.

The management of hepatocellular carcinoma. Current expert opinion and recommendations derived from the 24th ESMO/World Congress on Gastrointestinal Cancer, Barcelona, 2022.

This article summarises expert discussion on the management of patients with hepatocellular carcinoma (HCC), which took place during the 24th World Gastrointestinal Cancer Congress (WGICC) in Barcelona, July 2022. A multidisciplinary approach is mandatory to ensure an optimal diagnosis and staging of HCC, planning of curative and therapeutic options, including surgical, embolisation, ablative strategies, or systemic therapy. Furthermore, in many patients with HCC, underlying liver cirrhosis represents a challenge and influences the therapeutic options.

[Metastatic colorectal cancer-Modern treatment strategies and sequences]. / Metastasiertes kolorektales Karzinom ­ moderne Therapiestrategien und -sequenzen.

The treatment of metastatic colorectal cancer (mCRC) has been considerably expanded and relevantly improved in recent years with new strategies, such as resection of liver and/or lung metastases, induction and maintenance treatment, the establishment of targeted therapies and molecularly defined strategies in defined subgroups. This article presents evidence-based treatment options and algorithms, with a focus on systemic treatment.

Perioperative or only adjuvant gemcitabine plus nab-paclitaxel for resectable pancreatic cancer (NEONAX)-a randomized phase II trial of the AIO pancreatic cancer group.

BACKGROUND: Data on perioperative chemotherapy in resectable pancreatic ductal adenocarcinoma (rPDAC) are limited. NEONAX examined perioperative or adjuvant chemotherapy with gemcitabine plus nab-paclitaxel in rPDAC (National Comprehensive Cancer Network criteria). PATIENTS AND METHODS: NEONAX is a prospective, randomized phase II trial with two independent experimental arms. One hundred twenty-seven rPDAC patients in 22 German centers were randomized 1 : 1 to perioperative (two pre-operative and four post-operative cycles, arm A) or adjuvant (six cycles, arm B) gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2) on days 1, 8 and 15 of a 28-day cycle. RESULTS: The primary endpoint was disease-free survival (DFS) at 18 months in the modified intention-to-treat (ITT) population [R0/R1-resected patients who started neoadjuvant chemotherapy (CTX) (A) or adjuvant CTX (B)]. The pre-defined DFS rate of 55% at 18 months was not reached in both arms [A: 33.3% (95% confidence interval [CI] 18.5% to 48.1%), B: 41.4% (95% CI 20.7% to 62.0%)]. Ninety percent of patients in arm A completed neoadjuvant treatment, and 42% of patients in arm B started adjuvant chemotherapy. R0 resection rate was 88% (arm A) and 67% (arm B), respectively. Median overall survival (mOS) (ITT population) as a secondary endpoint was 25.5 months (95% CI 19.7-29.7 months) in arm A and 16.7 months (95% CI 11.6-22.2 months) in the upfront surgery arm. This difference corresponds to a median DFS (mDFS) (ITT) of 11.5 months (95% CI 8.8-14.5 months) in arm A and 5.9 months (95% CI 3.6-11.5 months) in arm B. Treatment was safe and well tolerable in both arms. CONCLUSIONS: The primary endpoint, DFS rate of 55% at 18 months (mITT population), was not reached in either arm of the trial and numerically favored the upfront surgery arm B. mOS (ITT population), a secondary endpoint, numerically favored the neoadjuvant arm A [25.5 months (95% CI 19.7-29.7months); arm B 16.7 months (95% CI 11.6-22.2 months)]. There was a difference in chemotherapy exposure with 90% of patients in arm A completing pre-operative chemotherapy and 58% of patients starting adjuvant chemotherapy in arm B. Neoadjuvant/perioperative treatment is a novel option for patients with resectable PDAC. However, the optimal treatment regimen has yet to be defined. The trial is registered with ClinicalTrials.gov (NCT02047513) and the European Clinical Trials Database (EudraCT 2013-005559-34).

The impact of endoscopic activity on musculoskeletal disorders of high-volume endoscopists in Germany.

Physical stress is common in GI endoscopists, leading to musculoskeletal disorders. Considering the increasing complexity of interventional GI endoscopy with prolonged examination time, work-related musculoskeletal disorders have come into focus. However, data on work-related health stress in German endoscopists are elusive. The aim of this study was therefore to investigate the prevalence and consequences of work-related musculoskeletal disorders in German endoscopists. A 24-item questionnaire on endoscopy-associated musculoskeletal disorders and standardized pain assessment was developed by an interdisciplinary team of endoscopists and sports medics. The survey was distributed online by the leading German societies for gastroenterology and endoscopy. Overall, 151 German practicing endoscopists took part in the study. Regarding the average number of endoscopic procedures per week, the study collective consisted mainly of high-volume endoscopists. The survey showed that most participants suffered from general musculoskeletal disorders (82.8%) and from work-related musculoskeletal disorders (76.8%). The most affected body parts were the neck, low back, thumb, and shoulder. Temporary absence from work due to symptoms was reported by 9.9% of the respondents. Over 30% of participating endoscopists stated the need for analgesics or physiotherapy due to musculoskeletal disorders. Age, professional experience and work time were identified as relevant risk factors for musculoskeletal health issues. A high number of German endoscopists are affected by musculoskeletal disorders due to specific working postures and repetitive movements with a large impact on personal health. Further interventional studies are mandatory to improve the risk prevention of endoscopic activity.

[Diagnostic Imaging of pancreatic carcinoma-Update of the new guideline]. / Diagnostik beim Pankreaskarzinom ­ Update in der neuen Leitlinie.

The new German S3 guidelines on ductal pancreatic adenocarcinoma were published for the first time on the homepage of the Association of the Scientific Medical Societies in Germany (AWMF) in December 2021 as a new update and thus the second update (first update 2013) and contain a large number of innovations in terms of diagnostics and treatment. The guidelines were organized and led by the German Society for Digestive and Metabolic Diseases (DGVS). In this article we would like to present the central content and innovations related to the radiological diagnostics of ductal pancreatic adenocarcinoma. The most important innovations are the highest recommendation strength in favor of computed tomography (CT) when assessing tumor spread as well as the adaptation of the European guidelines for cystic tumors by magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) as the method of first choice. A further innovation is the implementation of a structured reporting of CT findings for describing the anatomical tumor resectability on the basis of the publication presented by the Abdominal Imaging Working Group and the Oncological Imaging Working Group of the German Radiological Society. There is no evidence for the implementation of radiological imaging in the field of aftercare or in the field of screening.

Prognosis and tumor biology of pancreatic cancer patients with isolated lung metastases: translational results from the German multicenter AIO-YMO-PAK-0515 study.

BACKGROUND: Pulmonary metastasis (M1-PUL) as first site of dissemination in pancreatic ductal adenocarcinoma (PDAC) is a rare event and may define a distinct biological subgroup. PATIENTS AND METHODS: Arbeitsgemeinschaft Internistische Onkologie-Young Medical Oncologists-Pankreas-0515 study (AIO-YMO-PAK-0515) was a retrospective German multicenter study investigating clinical and molecular characteristics of M1-PUL PDAC patients; 115 M1-PUL PDAC patients from 7 participating centers were included. Clinical characteristics and potential prognostic factors were defined within the M1-PUL cohort. Archival tumor samples were analyzed for Her2/neu, HNF1A and KRT81 expression. Additionally, messenger RNA (mRNA) expression analysis (using a 770-gene immune profiling panel) was carried out in the M1-PUL and in a control cohort (M1-ANY). RESULTS: Median overall survival in the entire M1-PUL cohort was 20 months; the most favorable prognosis (median survival: 28 months) was observed in the subgroup of 66 PDAC patients with metachronous lung metastases after previous curative-intent surgery. The number of metastatic lesions, uni- or bilateral lung involvement as well as metastasectomy were identified as potential prognostic factors. Her2/neu expression and PDAC subtyping (by HNF1A and KRT81) did not differ between the M1-PUL and the M1-ANY cohort. mRNA expression analysis revealed significant differentially expressed genes between both cohorts: CD63 and LAMP1 were among the top 20 differentially expressed genes and were identified as potential mediators of organotropism and favorable survival outcome of M1-PUL patients. CONCLUSION: M1-PUL represents a clinically favorable cohort in PDAC patients. Site of relapse might already be predetermined at the time of surgery and could potentially be predicted by gene expression profiling.

Afatinib plus gemcitabine versus gemcitabine alone as first-line treatment of metastatic pancreatic cancer: The randomised, open-label phase II ACCEPT study of the Arbeitsgemeinschaft Internistische Onkologie with an integrated analysis of the 'burden of therapy' method.

BACKGROUND: Targeting the epidermal growth factor receptor pathway remains controversial in pancreatic cancer. Afatinib is an oral irreversible ErbB family blocker approved in non-small-cell lung cancer. This open-label, multicenter, randomised phase II trial evaluated gemcitabine plus afatinib (Gem/afatinib) versus gemcitabine (Gem) alone as first-line treatment for metastatic pancreatic cancer. PATIENTS AND METHODS: Patients were randomised in a 2:1 ratio to either Gem (1000 mg/m2 weekly for three weeks followed by one week of rest, repeated every four weeks) and afatinib (40 mg orally once daily) or Gem alone. Overall survival (OS) was the primary study end-point. The novel BOTh©™ methodology was implemented to derive a quantitative estimate for the 'Burden of Therapy/Toxicity' (BOTh) for each patient on every day during the clinical study. RESULTS: One hundred nineteen patients from 25 centres were randomised, 79 patients for Gem/afatinib and 40 for Gem. Median OS was 7.3 months in the Gem/afatinib arm versus 7.4 months in the Gem-alone arm (hazard ratio [HR]: 1.06, p = 0.80). Median progression-free survival was identical in both arms (3.9 months versus 3.9 months, HR: 0.85, p = 0.43). Adverse events were more frequent in the Gem/afatinib arm, especially diarrhoea (71% vs. 13%) and skin rash (65% vs. 5%). The BOTh©™ analysis revealed a significantly higher burden of toxicity in the combination arm (p = 0.0005). CONCLUSION: The addition of afatinib to Gem did not improve treatment efficacy and was more toxic. The BOTh©™ methodology allowed a detailed insight into the course of treatment-related adverse events over the study period. The trial was registered at clinicaltrials.gov (NCT01728818) and Eudra-CT (2011-004063-77).

Dynamics in treatment response and disease progression of metastatic colorectal cancer (mCRC) patients with focus on BRAF status and primary tumor location: analysis of untreated RAS-wild-type mCRC patients receiving FOLFOXIRI either with or without panitumumab in the VOLFI trial (AIO KRK0109).

PURPOSE: In mCRC, disease dynamics may play a critical role in the understanding of long-term outcome. We evaluated depth of response (DpR), time to DpR, and post-DpR survival as relevant endpoints. METHODS: We analyzed DpR by central review of computer tomography images (change from baseline to smallest tumor diameter), early tumor shrinkage (≥ 20% reduction in tumor diameter at first reassessment), time to DpR (study randomization to DpR-image), post-DpR progression-free survival (pPFS = DpR-image to tumor progression or death), and post-DpR overall survival (pOS = DpR-image to death) with special focus on BRAF status in 66 patients and primary tumor site in 86 patients treated within the VOLFI-trial, respectively. RESULTS: BRAF wild-type (BRAF-WT) compared to BRAF mutant (BRAF-MT) patients had greater DpR (- 57.6% vs. - 40.8%, p = 0.013) with a comparable time to DpR [4.0 (95% CI 3.1-4.4) vs. 3.9 (95% CI 2.5-5.5) months; p = 0.8852]. pPFS was 6.5 (95% CI 4.9-8.0) versus 2.6 (95% CI 1.2-4.0) months in favor of BRAF-WT patients (HR 0.24 (95% CI 0.11-0.53); p < 0.001). This transferred into a significant difference in pOS [33.6 (95% CI 26.0-41.3) vs. 5.4 (95% CI 5.0-5.9) months; HR 0.27 (95% CI 0.13-0.55); p < 0.001]. Similar observations were made for patients stratified for primary tumor site. CONCLUSIONS: BRAF-MT patients derive a less profound treatment response compared to BRAF-WT patients. The difference in outcome according to BRAF status is evident after achievement of DpR with BRAF-MT patients hardly deriving any further disease control beyond DpR. Our observations hint towards an aggressive tumor evolution in BRAF-MT tumors, which may already be molecularly detectable at the time of DpR.

Nal-IRI with 5-fluorouracil (5-FU) and leucovorin or gemcitabine plus cisplatin in advanced biliary tract cancer - the NIFE trial (AIO-YMO HEP-0315) an open label, non-comparative, randomized, multicenter phase II study.

BACKGROUND: Biliary tract cancer (BTC) has a high mortality. Primary diagnosis is frequently delayed due to mostly unspecific symptoms, resulting in a high number of advanced cases at the time of diagnosis. Advanced BTCs are in principle chemotherapy sensitive as determined by improved disease control, survival and quality of life (QoL). However, median OS does not exceed 11.7 months with the current standard of care gemcitabine plus cisplatin. Thereby, novel drug formulations like nanoliposomal-irinotecan (nal-IRI) in combination with 5- fluorouracil (5-FU)/leucovorin may have the potential to improve therapeutic outcomes in this disease. METHODS: NIFE is an interventional, prospective, randomized, controlled, open label, two-sided phase II study. Within the study, 2 × 46 patients with locally advanced, non-resectable or metastatic BTC are to be enrolled by two stage design of Simon. Data analysis will be done unconnected for both arms. Patients are allocated in two arms: Arm A (experimental intervention) nal-IRI mg/m2, 46 h infusion)/5-FU (2400 mg/m2, 46 h infusion)/leucovorin (400 mg/m2, 0.5 h infusion) d1 on 14 day-cycles; Arm B (standard of care) cisplatin (25 mg/m2, 1 h infusion)/gemcitabine (1000 mg/m2, 0.5 h infusion) d1 and d8 on 21 day-cycles. The randomization (1:1) is stratified for tumor site (intrahepatic vs. extrahepatic biliary tract), disease stage (advanced vs. metastatic), age (≤70 vs. > 70 years), sex (male vs. female) and WHO performance score (ECOG 0 vs. ECOG 1). Primary endpoint of the study is the progression free survival (PFS) rate at 4 months after randomization by an intention-to-treat analysis in each of the groups. Secondary endpoints are the overall PFS rate, the 3-year overall survival rate, the disease control rate after 2 months, safety and patient related outcome with quality of life. The initial assessment of tumor resectability for locally advanced BTCs is planned to be reviewed retrospectively by a central surgical board. Exploratory objectives aim at establishing novel biomarkers and molecular signatures to predict response. The study was initiated January 2018 in Germany. DISCUSSION: The NIFE trial evaluates the potential of a nanoliposomal-irinotecan/5-FU/leucovorin combination in the first line therapy of advanced BTCs and additionally offers a unique chance for translational research. TRIAL REGISTRATION: Clinicaltrials.gov NCT03044587. Registration Date February 7th 2017.

Genotyping of circulating tumor DNA in cholangiocarcinoma reveals diagnostic and prognostic information.

Diagnosis of Cholangiocarcinoma (CCA) is difficult, thus a noninvasive approach towards (i) assessing and (ii) monitoring the tumor-specific mutational profile is desirable to improve diagnosis and tailor treatment. Tumor tissue and corresponding ctDNA samples were collected from patients with CCA prior to and during chemotherapy and were subjected to deep sequencing of 15 genes frequently mutated in CCA. A set of ctDNA samples was also submitted for 710 gene oncopanel sequencing to identify progression signatures. The blood/tissue concordance was 74% overall and 92% for intrahepatic tumors only. Variant allele frequency (VAF) in ctDNA correlated with tumor load and in the group of intrahepatic CCA with PFS. 63% of therapy naive patients had their mutational profile changed during chemotherapy. A set of 76 potential progression driver genes was identified among 710 candidates. The molecular landscape of CCA is accessible via ctDNA. This could be helpful to facilitate diagnosis and personalize and adapt therapeutic strategies.

[Cystic pancreatic tumors: diagnostics and new biomarkers]. / Zystische Pankreastumoren: Diagnostik und neue Biomarker.

Mortality due to pancreatic ductal adenocarcinoma (PDAC) will increase in the near future. The only curative treatment for PDAC is radical resection; however, even small carcinomas exhibit micrometastases leading to early relapse. Accordingly, detection of premalignant precursor lesions is important. In essence, PDAC develops from three precursor lesions: pancreatic intraepithelial lesions (PanIN), intraductal papillary-mucinous neoplasia (IPMN) and mucinous-cystic neoplasia (MCN). Together with serous cystic neoplasia (SCN) and solid pseudopapillary neoplasia (SPN), these cystic lesions constitute the most common cystic neoplasms in the pancreas. In the case of IPMN, main and branch duct IPMN have to be differentiated because of a markedly different malignancy potential. While main duct IPMN and MCN have a high malignancy transformation rate, branch duct IPMNs are more variable with respect to malignant transformation. This shows that differential diagnosis of cystic lesions is important; however, this is often very difficult to accomplish using conventional imaging. Novel biomarkers and diagnostic tools based on the molecular differences of cystic pancreatic lesions could be helpful to differentiate these lesions and facilitate early diagnosis. The aim is to distinguish the premalignant cysts from strictly benign cystic lesions and a timely detection of malignant transformation. This article provides an overview on the molecular characteristics of cystic pancreatic lesions as a basis for improved diagnostics and the development of new biomarkers.

Esophageal stenting for benign and malignant disease: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE), endorsed by the European Society for Radiotherapy and Oncology (ESTRO), the European Society of Digestive Endoscopy (ESDO), and the European Society for Clinical Nutrition and Metabolism (ESPEN). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence. Main recommendations for malignant disease 1 ESGE recommends placement of partially or fully covered self-expandable metal stents (SEMSs) for palliative treatment of malignant dysphagia over laser therapy, photodynamic therapy, and esophageal bypass (strong recommendation, high quality evidence). 2 For patients with longer life expectancy, ESGE recommends brachytherapy as a valid alternative or in addition to stenting in esophageal cancer patients with malignant dysphagia. Brachytherapy may provide a survival advantage and possibly a better quality of life compared to SEMS placement alone. (Strong recommendation, high quality evidence.) 3 ESGE recommends esophageal SEMS placement as the preferred treatment for sealing malignant tracheoesophageal or bronchoesophageal fistula (strong recommendation, low quality evidence). 4 ESGE does not recommend the use of concurrent external radiotherapy and esophageal stent treatment. SEMS placement is also not recommended as a bridge to surgery or prior to preoperative chemoradiotherapy. It is associated with a high incidence of adverse events and alternative satisfactory options such as placement of a feeding tube are available. (Strong recommendation, low quality evidence.) Main recommendations for benign disease 1 ESGE recommends against the use of self-expandable stents (SEMSs) as first-line therapy for the management of benign esophageal strictures because of the potential for adverse events, the availability of alternative therapies, and costs (strong recommendation, low quality evidence). 2 ESGE suggests consideration of temporary placement of SEMSs as therapy for refractory benign esophageal strictures (weak recommendation, moderate evidence). Stents should usually be removed at a maximum of 3 months (strong recommendation, weak quality evidence). 3 ESGE suggests that fully covered SEMSs be preferred over partially covered SEMSs for the treatment of refractory benign esophageal strictures, because of their lack of embedment and ease of removability (weak recommendation, low quality evidence). 4 For the removal of partially covered esophageal SEMSs that are embedded, ESGE recommends the stent-in-stent technique (strong recommendation, low quality evidence). 5 ESGE recommends that temporary stent placement can be considered for treating esophageal leaks, fistulas, and perforations. The optimal stenting duration remains unclear and should be individualized. (Strong recommendation, low quality evidence.) 6 ESGE recommends placement of a SEMS for the treatment of esophageal variceal bleeding refractory to medical, endoscopic, and/or radiological therapy, or as initial therapy for patients with massive esophageal variceal bleeding (strong recommendation, moderate quality evidence).

[IgG4-associated diseases : State of the art]. / IgG4-assoziierte Erkrankung : Eine Standortbestimmung.

CLINICAL ISSUE: IgG4-related diseases are rare but the incidence is continuously increasing. The pathophysiology is only incompletely understood. Multiorgan involvement correlates with high relapse rates, high serum IgG4 levels and an aggressive disease course, which is why diagnostics and therapy must be carried out rapidly and efficiently according to international guidelines despite all the difficulties. STANDARD TREATMENT: Currently the therapeutic standard is initial therapy (induction therapy) with glucocorticosteroids over a longer period of time and if necessary followed by low-dose maintenance therapy. Steroids are also the first choice therapy for management of relapses. Refractory disease courses are a rare but relevant problem. TREATMENT INNOVATIONS: The B­cell depleting antibody rituximab has shown excellent results in terms of remission induction and also maintenance therapy. The good effectiveness profile is likely to change the current treatment regimen for IgG4-related diseases in the future. DIAGNOSTIC WORK-UP: The current diagnostic algorithms applicable for several organ systems are based on four major pillars: (i) patient history and physical examination, (ii) serological diagnostics, (iii) organ swelling in the appropriately selected imaging procedure and (iv) the histological picture as gold standard. PERFORMANCE: The currently used algorithms allow a diagnosis to be made in most cases. ACHIEVEMENTS: IgG4-related diseases are a relevant differential diagnosis, particularly of malignant diseases. It is often a diagnosis by exclusion. An interdisciplinary approach is essential for rapid diagnostics and induction of therapy. PRACTICAL RECOMMENDATIONS: In Europe IgG4 serum levels are just one of several diagnostic criteria. Imaging studies should be chosen according to the organ and disease manifestations.

"Miniguts" from plucked human hair meet Crohn's disease.

Human pluripotent stem cells represent a powerful tool to study human embryonic development and disease but also open up novel strategies for cell replacement therapies. Their capacity to give rise to every cell type of the human body, meanwhile, enables researchers to generate high yields of mesodermal, ectodermal, but also endodermal-derived tissues such as hepatic, pancreatic, or intestinal cells. Another progress in the field came with the advent of 3-dimensional culture conditions, so-called organoids, which facilitate maturation of stem cells and in turn more faithfully recapitulate human tissue architecture. While several studies reported the derivation of organoid cultures from adult intestinal tissue, the derivation of intestinal organoids derived from plucked human hair of Crohn's disease patients has not been reported. The current research project reports such successful generation and characterization of induced pluripotent stem cells (iPSCs) derived from hair sheet keratinocyte cultures of a patient with Crohn's disease. Stepwise differentiation along the intestinal lineage showed no differences in intermediate stages such as definitive endoderm formation. We also directed the patterned primitive gut tube toward intestinal organoids resembling the cellular architecture of human "miniguts". As expected from current pathophysiological knowledge on Crohn's disease, there were no obvious morphological differences in the "miniguts" derived from healthy control and diseased patient-induced pluripotent stem cells. Taken together, our platform will enable for detailed and complementary phenotyping of the pathophysiology of Crohn's disease in a novel disease-in-a-dish format.

[Obstacles and facilitators of conducting studies - the perspective of colorectal cancer centers' coordinators]. / Hemmende und fördernde Faktoren bei der Durchführung von Studien - Die Sicht von Darmkrebszentrumskoordinatorinnen und -koordinatoren.

INTRODUCTION: Clinical trials and health services research are crucial pillars for improving patient care. This paper examines factors inhibiting and promoting the study activity and the knowledge and use of trial registries (e. g. DRKS, StudyBox) as an opportunity to learn about existing studies. MATERIAL AND METHODS: The coordinators of 274 cancer center sites certified according to the requirements of the German Cancer Society were surveyed using a standardized online questionnaire. Data were analyzed using descriptive and bivariate statistics to identify associations with characteristics of the sites (e. g. patient volume, ownership, teaching status). RESULTS: 176 sites participated in the survey (64.2 %). The central obstacle to study participa-tion from the centers' view is the low number of existing studies. General knowledge of the population about studies was considered low. Trial registries are known to almost all respondents, but are rarely used. DISCUSSION: The results of the survey suggest that comprehensive measures are needed to sustainably increase the study activity. These include, for example, better information about studies, for example through appropriate databases, and (industry-independent) research funding. One possible way to sensitize patients for studies could be the comprehensive education of the population about the purpose of studies.

[ASCO-update 2015 - highlights of the 51. meeting of the american society of clinical oncology/ASCO 2015]. / ASCO-Update 2015 - Neuigkeiten vom 51. Meeting der American Society of Clinical Oncology/ASCO 2015.

The field of gastrointestinal oncology is rapidly developing, on the one hand through the identification of novel molecular targets and therapeutic principles, on the other hand through the establishment and improvement of multidisciplinary treatment strategies. The following manuscript summarizes the most important trial results of the ASCO Meeting 2015 for gastrointestinal cancers. Besides trials on perioperative treatment of esophageal-, pancreatic- and colon cancer, we will present impressive data on new therapeutic strategies such as immunotherapy in gastric-, liver and microsatellite instable colorectal cancer. The trials will be put into context by the authors.

Caliber of the common bile duct: effect of cholecystectomy and other factors in a ultrasonographic study of 8534 patients.

OBJECTIVE: The objective of the present study was to analyze the effects of different factors impacting the caliber of the common bile duct (CBD) and a comparison of maximum extrahepatic bile duct caliber in patients with and without a history of cholecystectomy. MATERIAL AND METHODS: A retrospective data analysis was undertaken of 8534 patients (4480 females; 4054 males; average age: 59.2±18.0 years) with sonographic documentation of bile duct caliber. Maximum intra- and extrahepatic bile duct diameters were studied. The normal maximum diameter of the extrahepatic bile duct was defined as 7 mm. In patients who had undergone prior cholecystectomy, a maximum bile duct diameter<10 mm was considered normal. RESULTS: The average maximum diameter of the CBD amounted to 5.3±3.0 mm for the overall collective. In patients who had undergone prior cholecystectomy, maximum CBD diameters in the normal range (<7 mm) were documented in 55%, while larger diameters (>7 mm) were observed in 45%. In the collective of patients without prior cholecystectomy, CBD diameters in the normal range (<7 mm) were found in 81%, with larger diameters observed in only 18.4% of patients. In both subgroups, there was a significant association between age and bile duct diameter (for those with prior cholecystectomy, p=0.0003; without prior cholecystectomy, p<0.0001). No statistically significant influence on CBD diameter was observed for either prior cholecystectomy (p=0.2116) or time interval since cholecystectomy (p=0.3537). Females, both with and without a history of prior cholecystectomy, showed a 1.4-1.5-fold higher risk of exhibiting a CBD diameter>7 mm (for those with prior cholecystectomy, p=0.0485; without prior cholecystectomy, p<0.001). CONCLUSIONS: Our data show a positive correlation between age and CBD diameter. There was no statistically significant relationship between CBD diameter and prior cholecystectomy, postoperative interval and BMI.