[Irritable bowel syndrome and functional dyspepsia : Diagnosis and treatment]. / Reizdarmsyndrom und funktionelle Dyspepsie : Diagnostik und Therapie.

Irritable bowel syndrome (IBS) and functional dyspepsia are chronic diseases of the digestive tract that challenge both patients and physicians due to their difficult diagnosis and limited treatment options. The international Rome IV diagnostic criteria are commonly used for research purposes. For IBS, the diagnostic criteria based on the German S3 guideline offer a less complicated alternative for everyday clinical practice. A thorough history and basic diagnostic work-up are essential for diagnosis, as reliable biomarkers are still lacking. Clinical manifestations of both disorders are variable, and it has been useful to allocate subtypes based on leading symptom clusters; these may facilitate the choice of diagnostic tests as well as symptomatic treatment approaches. Used correctly, the combination of available drug (mostly off-label) and non-drug options can help to reduce symptoms and improve quality of life.

Classifying the severity of acute pancreatitis: towards a way forward.

BACKGROUND: The recent development of two different severity classifications for acute pancreatitis has appropriately raised questions about which should be used. The aim of this paper is to review the two new severity classifications, outline their differences, review validation studies, and identify gaps in knowledge to suggest a way forward. METHODS: A literature review was performed to identify the purposes and differences between the classifications. Validation studies and those comparing the two different classifications were also reviewed. RESULTS: The Revised Atlanta Classification (RAC) and the Determinants Based Classification (DBC) both rely on assessment of local and systemic factors. The differences between the classifications provides opportunities for further research to improve the accuracy and utility of severity classification. This includes understanding how best to tailor severity classification to setting (e.g. secondary or tertiary hospital) and purpose (e.g. clinical management or research). A key difference is that the RAC does not consider infected pancreatic necrosis an indicator of severe disease. There is also the need to develop methods for the accurate non-invasive diagnosis of infected necrosis and evaluation of the characteristics of organ dysfunction in relation to severity and outcome. CONCLUSION: Further improvement in severity classification is possible and research priorities have been identified. For now, the decision as to which classification to use should be on the basis of setting, validity, accuracy, and ease of use.

English language version of the S3-consensus guidelines on chronic pancreatitis: Definition, aetiology, diagnostic examinations, medical, endoscopic and surgical management of chronic pancreatitis.

Chronic pancreatitis is a disease of the pancreas in which recurrent inflammatory episodes result in replacement of pancreatic parenchyma by fibrous connective tissue. This fibrotic reorganization of the pancreas leads to a progressive exocrine and endocrine pancreatic insufficiency. In addition, characteristic complications arise, such as pseudocysts, pancreatic duct obstructions, duodenal obstruction, vascular complications, obstruction of the bile ducts, malnutrition and pain syndrome. Pain presents as the main symptom of patients with chronic pancreatitis. Chronic pancreatitis is a risk factor for pancreatic carcinoma. Chronic pancreatitis significantly reduces the quality of life and the life expectancy of affected patients. These guidelines were researched and compiled by 74 representatives from 11 learned societies and their intention is to serve evidence-based professional training as well as continuing education. On this basis they shall improve the medical care of affected patients in both the inpatient and outpatient sector. Chronic pancreatitis requires an adequate diagnostic workup and systematic management, given its severity, frequency, chronicity, and negative impact on the quality of life and life expectancy.

[Motility disorders of the small intestine]. / Motilitätsstörungen des Dünndarms.

Chronic intestinal pseudo-obstruction (CIPO) is the most severe form of intestinal motility disorder, which leads to chronic or intermittent symptoms and signs of (sub-)ileus despite the absence of an intestinal obstruction. Small bowel motility disturbances may occur as primary diseases or secondary to a large number of other diseases and disturbances including rheumatological diseases and neurotoxic drugs. Pathological alterations affect the nervous system, smooth muscles, and/or mesenchymal structures such as the interstitial cells of Cajal or glia cells. Clinical symptoms are unspecific so that the initially suspected diagnosis is almost always wrong. Thus, extensive and stepwise diagnostic procedures are required involving specialized centers in order to exclude intestinal obstruction, to search for complications and potential causes of the disease, to quantify the extension and severity of the motility disorder, and to clarify the pathomechanism if possible. General therapeutic goals include maintenance of adequate nutritional status, improvement of propulsive motility, amelioration of abdominal symptoms, and avoidance and/or therapy of complications. Some CIPO patients require permanent parenteral nutrition. If this causes intolerable complications, small bowel transplantation can be considered in suitable patients as ultima ratio.

[Pain therapy in irritable bowel syndrome]. / Schmerztherapie beim Reizdarmsyndrom.

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal diseases. It is characterized by chronic abdominal pain, typically associated with altered bowel habits that cannot be explained by structural abnormalities in routine diagnostic workup. Based on the predominant symptom, IBS can be divided into different subtypes: IBS with predominant constipation, diarrhea, bloating, or pain. Knowledge about the complex and multifactorial IBS pathophysiology has increased tremendously in recent years, e.g., IBS may be related to alterations in gastrointestinal motility, visceral sensitivity, and the mucosal immune system. It is important, both for the patient and the physician, that IBS diagnosis is made quickly and thoroughly based on the typical symptom complex and exclusion of relevant differential diagnoses and to reassure the patient that IBS is a chronic, but benign disease. These components are the fundamental basis for a good patient-physician relationship and for a successful long-term management of this potentially very compromising disorder. IBS therapy is based on general measures as well as symptom-oriented medical therapy, where improvement of abdominal pain is one of the main goals in treating IBS patients. Several pain treatment options are available, which may be used long-term or on demand and which may be combined with other therapies. General medical approaches include antispasmodics, improvement of bowel function, phytotherapy, and probiotics. Especially in patients with psychological comorbidities, antidepressants may be used. Modern drug treatments include the GC-C agonist linaclotide in IBS with predominant constipation, the locally acting antibiotic rifaximin in IBS with bloating, and 5-HT3 antagonists in IBS with predominant diarrhea. Psychotherapy should be included in an interdisciplinary approach in refractory cases or in psychological comorbidity.

[International multidisciplinary classification of acute pancreatitis severity: the 2013 Spanish edition]. / Clasificación Internacional y Multidisciplinaria de la Pancreatitis Aguda: Edición Española 2013.

OBJECTIVE: To develop a new classification of acute pancreatitis severity on the basis of a sound conceptual framework, comprehensive review of the published evidence, and worldwide consultation. BACKGROUNDS: The Atlanta definitions of acute pancreatitis severity are ingrained in the lexicon of specialist in pancreatic diseases, but are suboptimal because these definitions are based on the empiric description of events not associated with severity. METHODS: A personal invitation to contribute to the development of a new classification of acute pancreatitis severity was sent to all surgeons, gastroenterologists, internists, intensivists and radiologists currently active in the field of clinical 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 organized to bring contributors from different disciplines together and discuss the concept and definitions. RESULTS: The new classification of severity is based on the actual local and systemic determinants of severity, rather than on the description of events that are non-causally associated 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, whereby the presence of both infected (peri) pancreatic necrosis and persistent organ failure has a greater impact upon severity than either determinant alone. The derivation of a classification based on the above principles results in four categories of severity: mild, moderate, severe, and critical. CONCLUSIONS: This classification is the result of a consultative process among specialists in pancreatic diseases 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.

[Determinant-based classification of acute pancreatitis severity. International multidisciplinary classification of acute pancreatitis severity: the 2013 German edition]. / Einteilung des Schweregrads der akuten Pankreatitis. Internationale, multidisziplinäre klinische Klassifikation auf Basis pathogenetischer Determinanten: Deutsche Version 2013.

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.

[Multidisciplinar international classification of the severity of acute pancreatitis: Italian version 2013]. / Classificazione Internazionale Multidisciplinare della Gravità della Pancreatite Acuta Versione Italiana 2013.

AIM: The aim of this paper was to present the 2013 Italian edition of a new international classification of acute pancreatitis severity. The Atlanta definitions of acute pancreatitis severity are ingrained in the lexicon of pancreatologists but suboptimal because these definitions are based on empiric description 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, intensivists, and radiologists who are currently active in clinical research on acute pancreatitis. A global web-based survey was conducted and a dedicated international symposium was organized to bring contributors from different disciplines together and discuss the concept and definitions. RESULTS: The new international classification is based on the actual local and systemic determinants of severity, rather than description 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. CONCLUSION: This classification 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.

[Functional gastrointestinal diseases]. / Funktionelle Magen-Darm-Erkrankungen.

Functional dyspepsia (FD) and irritable bowel syndrome (IBS) are the most important functional gastrointestinal diseases (FGID), and both affect about 5-15 % of the German population. The patients' symptoms are caused by disturbances of gastrointestinal (GI) motility, secretion and sensitivity. Central processing of visceral afferences is disturbed, and the course of the disease and individual symptom perception are influenced by psychosocial factors. Diagnosis of FD and IBS is based on a compatible symptom pattern, absence of alarm symptoms and exclusion of relevant differential diagnoses. The diagnosis of FD requires a normal upper GI endoscopy. Current German guidelines also demand a normal colonoscopy for diagnosis of IBS. Basic therapeutic measures include explanation of the nature of the disease and its harmlessness quo ad vitam . Individual trigger factors should be identified and eliminated if possible. Drug therapy of persisting complaints is guided by the dominant symptom.

[Rational and efficient diagnosis in different stages of Crohn's disease]. / Rationale und rationelle Diagnostik in unterschiedlichen Krankheitsphasen des Morbus Crohn.

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.

[IBD ahead 2010--Answering important questions in Crohn's disease treatment]. / IBD ahead 2010--Antworten auf zehn zentrale Fragen in der aktuellen Therapie des Morbus Crohn.

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.

Crust formation and plate motion in the early archean.

Mounting evidence for voluminous continental crust formation in the early Archean involving intracrustal melting and selective preservation of granitoid rocks suggests that initial crust formation crust formation and growth were predominantly by magmatic underplating in plumegenerated Iceland-type settings. Collision of these early islands to give rise to larger blocks is suggested by extensive horizontal shortening in both supracrustal and granitoid assemblages. Preservation of early Archean high-grade gneisses that were once at depths of 20 to 30 kilometers implies that these blocks developed thick, subcrustal roots despite high mantle heat flow. Rigid continental plates must have existed since at least 3.5 billion years ago, and greenstone belts (composed of mixed metavolcanic and metasedimentary sequences intruded by granitoid plutons) probably developed on or near these microcontinents. Paleomagnetic data with good age control from at least one ancient craton suggest that plate motion was at normal minimum average velocities of about 17 millimeters per year with respect to the poles during the period 3.5 billion to 2.4 billion years ago. If this is true on a global scale, Archean plate motion was not faster than in later geologic times.

S3-guideline "helicobacter pylori and gastroduodenal ulcer disease" of the German society for digestive and metabolic diseases (DGVS) in cooperation with the German society for hygiene and microbiology, society for pediatric gastroenterology and nutrition e. V., German society for rheumatology, AWMF-registration-no. 021 / 001.

This guideline updates a prior consensus recommendation of the German Society for Digestive and Metabolic Diseases (DGVS) from 1996. It was developed by an interdisciplinary cooperation with representatives of the German Society for Hygiene and Microbiology, the Society for Pediatric Gastroenterology and Nutrition (GPGE), and the German Society for Rheumatology. The guideline is methodologically based on recommendations of the Association of the Scientific Medical Societies in Germany (AWMF) for providing a systematic evidence-based S 3 level consensus guideline and has also implemented grading criteria according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) process. Clinical applicability of study results as well as specifics for Germany in terms of epidemiology, antibiotic resistance status, diagnostics, and therapy were taken into account.

Characterisation of cholinesterase expression during murine embryonic stem cell differentiation.

It is already established that cholinesterases (ChEs) appear in every embryonic blastema at a very early stage of development, independently from innervation. Embryonic butyrylcholinesterase (BChE) is typically found in cells engaged in proliferation processes, while acetylcholinesterase (AChE) is expressed by cells undergoing morphogenetic processes. In order to better define the regulation of cholinesterases during development, we examined their expressions during in vitro differentiation of two murine embryonic stem cell lines by reverse transcription polymerase chain reaction, histochemistry and enzyme activity measurements. AChE and BChE activity and mRNA were present in the undifferentiated stem cells. To test whether the ChEs expression is regulated during differentiation, we employed the embryoid bodies (EBs) culture method, allowing the cells to differentiate, to then collect them at various stages in culture. Interestingly, phases of differentiation were accompanied by increased AChE transcripts; BChE expression was constant, decreasing at later differentiation stages. Cholinesterase activities showed corresponding patterns, with AChE activity increasing at later stages in culture and BChE slightly decreasing. Histochemistry revealed that AChE and BChE activities were mutually exclusive, being expressed by different cell subpopulations. Thus, we have demonstrated that mouse embryonic stem cells express cholinesterases, the enzymes are functional and their expression is regulated during differentiation. Therefore, it appears that their functions under these conditions are not related to synaptic transmission, but for the developmental processes.

Laparoscopic fundoplication: Nissen versus Toupet two-year outcome of a prospective randomized study of 200 patients regarding preoperative esophageal motility.

OBJECTIVE: To determine the influence of preoperative esophageal motility on clinical and objective outcome of the Toupet or Nissen fundoplication and to evaluate the success rate of these procedures. Nissen fundoplication (360 degrees ) is the standard operation in the surgical management of gastroesophageal reflux disease (GERD). In order to avoid postoperative dysphagia it has been proposed to tailor antireflux surgery according to pre-existing esophageal motility. Postoperative dysphagia is thought to occur more commonly in patients with esophageal dysmotility and it has been recommended to use the Toupet procedure (270 degrees ) in these patients. We performed a randomized trial to evaluate this tailored concept and to compare the two operative techniques concerning reflux control and complication rate (dysphagia). METHODS: 200 patients with GERD were included in a prospective, randomized study. After preoperative examinations (clinical interview, endoscopy, 24-hour pH-metry and esophageal manometry) 100 patients underwent either a laparoscopic Nissen procedure (50 with and 50 without motility disorders), or Toupet (50 with and 50 without motility disorders). Postoperative follow-up after two years included clinical interview, endoscopy, 24-hour pH-metry, and esophageal manometry. RESULTS: After two years 85% (Nissen) and 85% (Toupet) of patients were satisfied with the operative result. Dysphagia was more frequent following a Nissen fundoplication compared to Toupet (19 vs. 8, p < 0.05) and did not correlate with preoperative motility. Concerning reflux control the Toupet proved to be as good as the Nissen procedure. CONCLUSION: Tailoring antireflux surgery according to the esophageal motility is not indicated, as motility disorders are not correlated with postoperative dysphagia. The Toupet procedure is the better operation as it has a lower rate of dysphagia and is as good as the Nissen fundoplication in controlling reflux.