[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.

An expert consensus definition of failure of a treatment to provide adequate relief (F-PAR) for chronic constipation - an international Delphi survey.

BACKGROUND: As treatments for constipation become increasingly available, it is important to know when to progress along the treatment algorithm if the patient is not better. AIM: To establish the definition of failure of a treatment to provide adequate relief (F-PAR) to support this management and referral process in patients with chronic constipation. METHODS: We conducted an international Delphi Survey among gastroenterologists and general practitioners with a special interest in chronic constipation. An initial questionnaire based on recognised rating scales was developed following a focus group. Data were collected from two subsequent rounds of questionnaires completed by all authors. Likert scales were used to establish a consensus on a shorter list of more severe symptoms. RESULTS: The initial focus group yielded a first round questionnaire with 84 statements. There was good consensus on symptom severity and a clear severity response curve, allowing 67 of the symptom-severity pairings to be eliminated. Subsequently, a clear consensus was established on further reduction to eight symptom statements in the final definition, condensed by the steering committee into five diagnostic statements (after replicate statements had been removed). CONCLUSIONS: We present an international consensus on chronic constipation, of five symptoms and their severities, any of which would be sufficient to provide clinical evidence of treatment failure. We also provide data representing an expert calibration of commonly used rating scales, thus allowing results of clinical trials expressed in terms of those scales to be converted into estimates of rates of provision of adequate relief.

Prolonged measurement improves the assessment of the barrier function of the esophago-gastric junction by high-resolution manometry.

BACKGROUND: Etiology of gastro-esophageal reflux disease (GERD) is multifactorial, but incompetence of the esophago-gastric junction (EGJ) appears to be of crucial importance. Established manometric parameters for assessment of EGJ barrier function are sub-optimal, potentially because they reflect only a very brief (up to 30 seconds), not necessarily representative period. This prospective, case-control study tested the performance of novel, high-resolution manometry (HRM) parameters of EGJ function in the assessment of GERD. METHODS: Patients with reflux symptoms and healthy controls (HC) underwent standard HRM and 24-hour pH±impedance measurements. EGJ morphology, lower esophageal sphincter pressure integral (LES-PI), EGJ contractile integral (EGJ-CI) were compared with total-EGJ-CI, a novel parameter summarizing EGJ barrier function during the entire HRM protocol. Esophageal acid exposure ≥4.2%/24 h (A-Reflux-pos) or ≥73 reflux episodes in 24 hours (V-Reflux-pos) were considered pathological. KEY RESULTS: Sixty five HC and 452 patients completed HRM, 380 (84%) patients underwent ambulatory reflux-monitoring. LES-PI, EGJ-CI and total-EGJ-CI correlated with EGJ morphology subtypes (all P<.00001). Only total-EGJ-CI was consistently lower in A-Reflux-pos and V-Reflux-pos subjects compared with HC and patients without GERD. Total-EGJ-CI was also the single best parameter for prediction of pathological reflux (optimal cut-off 47 mmHg cm, AUC 0.746, P<.0001). This cut-off value, approximately 1 SD below the mean normal value, showed modest sensitivity 54% and positive predictive value 46%, but good specificity 85% and negative predictive value 89% for GERD diagnosis. CONCLUSION & INFERENCES: Total EGJ-CI, a new metric that summarizes EGJ contractility over time, allows an improved assessment of EGJ barrier function. Pathological reflux is unlikely if this metric is within the upper two-thirds of the normal range.

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.

[Acute colonic pseudo-obstruction: Ogilvie syndrome]. / Akute Kolonpseudoobstruktion: Ogilvie-Syndrom.

Acute colonic pseudo-obstruction (ACPO) is characterized by marked colonic dilatation which develops over several days. ACPO is due to a motility disorder and is not caused by colonic obstruction and occurs in patients with severe, often acute underlying diseases or postoperatively. It is associated with a 25-30% mortality overall that increases to up to 50% in patients who develop complications (e.g. colonic ischemia and perforation). The pathogenesis of the disorder has not yet been clarified and clinical symptoms and signs are relatively unspecific. In particular, ACPO has to be differentiated from colonic obstruction and toxic megacolon. For this blood tests and radiological tests are required, e.g. plain abdominal radiograph, abdominal computed tomography (CT) and water soluble contrast enema, which are also required for detection of complications. Patients with ACPO should generally receive supportive therapy for decompression of the gastrointestinal tract (e.g. gastric and rectal tubes) and to minimize predisposing factors. In most uncomplicated cases this leads to resolution of colonic dilatation. Clinical and radiological controls at close intervals are required until the condition is resolved. If patients do not respond within 1-2 days or if ACPO has already reached a critical duration (>3-4 days) or extent (i.e. cecal diameter ≥12 cm), neostigmine should be administered and leads to durable success in approximately 3 out of 4 patients. Patients who are still refractory to treatment should receive endoscopic decompression. More invasive therapeutic options, such as cecostomy or (segmental) colonic resection should only be considered for patients who still do not respond to treatment or present with the abovementioned complications.

[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.

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.

Randomized, controlled trial of 2 L polyethylene glycol plus ascorbate components versus sodium phosphate for bowel cleansing prior to colonoscopy for cancer screening.

BACKGROUND: Colonoscopy requires effective bowel preparation for adequate mucosal visualization. Safety and acceptability of bowel preparation are key components in colorectal cancer screening (CRC) populations. OBJECTIVE: To compare the efficacy, safety and acceptability of bowel preparation with polyethylene glycol (PEG), ascorbic acid, sodium ascorbate (ascorbate components), sodium sulfate and electrolytes (PEG+Asc) or sodium phosphate (NaP). METHODS: Consenting adults undergoing elective out-patient colonoscopy for CRC were randomized to take 2 L PEG+Asc or 90 mL NaP (control) following manufacturer's instructions. PEG+Asc was taken the evening before and morning of the colonoscopy; NaP was taken the morning and evening before colonoscopy. Participants followed a restricted diet specific to each preparation. Primary endpoint was bowel cleansing success (100% colon mucosa visible) rated by an independent expert panel (all experienced endoscopists) unaware of treatment allocations. Subject reported outcomes about the preparations were elicited. Adverse events were recorded. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov: NCT00427089. RESULTS: Successful bowel cleansing rate was significantly higher in the PEG+Asc (N = 242) than the NaP (N = 114) group (PEG+Asc 93.4% [95% CI 89.5-96.2] versus NaP 22.8% [15.5-31.6%], p < 0.0001). Subject reported outcomes on acceptability of the two different preparations were not significantly different (p = 0.238). However, taste ratings for PEG+Asc were significantly better versus NaP (mean VAS: 31.2 and 38.1 respectively, p = 0.0111). The proportion of patients prepared to receive the same preparation again was significantly higher in the PEG+Asc group (88.4% vs. 78.1%, p < 0.0001). CONCLUSIONS: PEG+Asc provided superior bowel cleansing to NaP and was well tolerated. Findings for PEG+Asc are aligned with previous similar studies; however, differences observed in NaP cleansing results, especially for the proximal colon segments, may be due to factors including: differences in demographics and population types and the use of the validated Harefield Cleansing Scale as an assessment tool combined with expert reviews, which may have resulted in conservative cleansing assessments.

[Eating disorder or gastrointestinal disease? Massive weight loss and abdominal complaints in a 13-year-old girl]. / Essstörung oder gastroenterologische Erkrankung? Bedrohlicher Gewichtsverlust und abdominelle Beschwerden bei einem 13-jährigen Mädchen.

MEDICAL HISTORY: In a 13-year-old girl regurgitation, constipation and postprandial abdominal pain developed, with decreased nutrient uptake and severe weight loss (BMI 12,6) following a gastroenteritis 2 years before. An eating disorder had been strongly suspected but this diagnosis was not accepted by the family. DIAGNOSTICS: Initial investigations including physical investigation, elaborate laboratory tests and imaging techniques showed normal results, but we found transit disturbances and hypotensive motility of the upper gastrointestinal tract. Therapy and course of disease: During prokinetic treatment the girl was asymptomatic for about 9 months, but then the symptoms recurred and no longer responded to drug treatment. Feeding via a jejunal tube because of severe malnutrition was not tolerated either. Refractory vomiting and life-threatening hypokalemia and alkalosis occurred. Imaging techniques now showed marked dilatation of the proximal duodenum. Laparotomy was performed because a Wilkie's syndrome was suspected. However, during the operation mesenterial malrotation was found with adhesive fixation of the distal ileum in the upper left abdomen and compression of the proximal jejunum. The malrotation had been possible because the proximal colon was hypermobile. Following correction of the anatomical situation and retroperitoneal fixation of the colon, oral nutrition was well tolerated. The girl gained weight and remained symptom-free. CONCLUSIONS: Not only eating disorders but also defined gastroenterological disturbances may cause weight loss and abdominal symptoms in adolescent girls, even in patients with suggestive symptoms and without pathological findings with routine diagnostics.

[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.

Review article: Linaclotide for the management of irritable bowel syndrome with constipation.

BACKGROUND: Irritable bowel syndrome with constipation (IBS-C) represents a significant burden to patients and healthcare systems due to its prevalence and lack of successful symptomatic resolution with established treatment options. Linaclotide 290 µg has recently been approved by the European Medicines Agency (EMA) for moderate-to-severe IBS-C and by the US Food and Drug Administration for IBS-C (290 µg dose) and for chronic constipation (145 µg dose). AIM: To summarise data leading to the approval of linaclotide for IBS-C, with focus on EMA-pre-specified outcome measures. METHODS: Literature search of a peer-review database (PubMed) and review of congress abstracts on linaclotide preclinical and clinical trial data in IBS-C. RESULTS: Preclinical studies suggest that the guanylate cyclase C agonist (GCCA) linaclotide acts through elevation of cyclic guanosine monophosphate (cGMP) levels, leading to accelerated gastrointestinal (GI) transit through increased fluid secretion and reduced visceral hypersensitivity. Clinical trial data demonstrate that linaclotide improves abdominal symptoms (pain, bloating) and bowel symptoms (constipation) compared with placebo in patients with IBS-C. The most frequent side effect, diarrhoea, results from the therapeutic action of linaclotide. Linaclotide acts locally in the GI tract with minimal systemic exposure, resulting in low oral bioavailability and thus a low risk of relevant systemic adverse effects. CONCLUSION: Linaclotide, a first-in-class GCCA, is a promising new drug with a novel, dual mechanism of action that, unlike more well-established agents, can relieve the abdominal pain, bloating and constipation associated with IBS-C and has a low propensity for systemic side effects.

[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.

[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.

[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.