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.

Esophageal function tests are not helpful in symptoms suspicious of extraesophageal reflux - a prospective study in 74 patients.

BACKGROUND/AIMS: Symptoms suspicious of extraesophageal reflux (SSEER) include globus, chronic cough, mucous obstruction and hoarseness. Reports of conventional esophageal function tests and measurement of extraesophageal reflux (EER) in these patients are spare providing conflicting results. METHODS: In a prospective study we evaluated 60 patients with SSEER by esophageal function tests (esophageal manometry, combined 24 h pH - metry - impedance and oropharyngeal pH measurement, Dx - pH measurement) and esophagogastroduodenoscopy (EGD). The patients were stratified into 2 groups according to their accompanying reflux symptoms. Group 1, n = 23, comprised patients with SSEER solely and group 2, n = 37 patients with SSEER and reflux symptoms. The patients were compared to patients with reflux symptoms solely (group 3, n = 14). RESULTS: There were no significant differences between the groups according to age, sex and BMI. Patients with SSEER and reflux symptoms (group 2) showed significantly increased proportion of pathological acid reflux, de Meester Score, pH < 4 overall and in upright positon and hypotensive lower esophageal sphincter pressure compared to patients with SSEER solely (group 1) but no significant difference to patients with reflux symptoms solely (group 3). All the other parameters of esophageal testing including non-acid reflux and EER were not significantly different between the three groups. CONCLUSION: The results of the present study do not support a causal link between SSEER and esophageal motility disorders, acid or non-acid reflux and EER as measured by conventional esophageal function tests and oropharyngeal pH measurement.

Clinical impact of esophageal function tests and argon plasma coagulation in heterotopic gastric mucosa of the esophagus and extraesophageal reflux symptoms - a prospective study.

BACKGROUND/AIMS: Globus, chronic cough, mucous obstruction and hoarseness are frequently interpreted and classified as manifestation of extraesophageal reflux (EER) or laryngopharyngeal reflux (LPR). Recent studies have indicated that ablation of heterotopic gastric mucosa of the proximal esophagus (HGMPE) by argon plasma coagulation (APC) significantly reduces EER/LPR symptoms. METHODS: In a prospective study we evaluated 14 patients with HGMPE and EER/LPR symptoms by esophageal function testing (esophageal manometry, combined 24 h-pH-metry-impedance - oropharyngeal-pH measurement), standardized symptom questionnaire (visual analogue scales), and esophagealgastroduodenoscopy (EGD). The patients were stratified into 3 groups: GERD (n = 5), functional heartburn (n = 5) and non-GERD-non-functional heartburn (n = 4). Patients (n = 12) received endoscopic ablation of HGMPE by APC. RESULTS: 73 % of the patients responded to APC with a reduction of frequency and intensity of their EER/LPR symptoms. The response to APC varied between the quality of symptoms and was most frequently seen in globus, swallowing difficulty and mucous obstruction. The magnitude of symptom reduction was highest in heartburn, sore throat, and globus. The response to APC was comparable between the three groups of patients irrespective of GERD and the presence or absence of reflux symptoms. Although 50 % of the patients showed an increased Ryan Score as measured by acid reflux in the posterior oropharynx, comparison between responders and non-responders to APC showed no significant differences with regard to symptom quality, acid and non-acid reflux, LES resting pressure, esophageal motility and Ryan Score. CONCLUSION: The study indicates that a large proportion of patients with HGMPE and EER/LPR symptoms responded to APC. However, we could not demonstrate a clinical or functional parameter that differentiated between responders and non-responders to APC or could predict the response to APC.

[Chest pain - not always the heart! Clinical impact of gastrointestinal diseases in non-cardiac chest pain]. / Brustschmerz - nicht immer das Herz! Klinische Bedeutung gastrointestinaler Erkrankungen beim nicht-kardialen Thoraxschmerz.

Non cardiac chest pain (NCCP) are recurrent angina pectoris like pain without evidence of coronary heart disease in conventional diagnostic evaluation. The prevalence of NCCP is up to 70 % and may be detected in this order at all levels of the medical health care system (general practitioner, emergency department, chest pain unit, coronary care). Reduction of quality of life in NCCP is comparable, partially even higher compared to cardiac chest pain. Reasons for psychological strain are symptom recurrence in app. 50 %, nonspecific diagnosis with resulting uncertainty and insufficient integration of other medical disciplines in diagnostic work-up. Managing of patients with NCCP has to be interdisciplinary because non cardiac causes of chest pain may be found frequently. Especially gastroenterological expertise is required because in 50 - 60 % of cases gastroesophageal reflux disease (GERD), in 15 - 18 % hypercontractile esophageal motility disorders with nutcracker, jackhammer esophagus or distal esophageal spasmus or achalasia and in 32 - 35 % other esophageal alterations (e. g. infectious esophageal inflammation, drug-induced ulcer, rings, webs, eosinophilic esophagitis) as cause of chest pain may be detected. This implicates that regular interdisciplinary round wards and management of chest pain units are mandatory.

[Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options]. / Systemische Mastzellaktivierungserkrankung: Ein praxisorientierter Leitfaden zu Diagnostik und Therapie.

In the present paper clinical phenotypes, pathogenetic relationships, and diagnostic algorithms as well as therapeutic concepts of/for systemic mast cell activation disease are reviewed. The reader should be able to recognize and diagnose a systemic mast cell activation disease, as well as to counsel a personalized drug therapy. In the case of chronic multisystem polymorbidity systemic mast cell activation disease should be considered as a differential diagnosis at an early stage. In most cases, specific, little invasive investigations allow diagnosing the disease and, hence, an appropriate therapy can be initiated.

Prospective and randomized study to evaluate the clinical impact of cap assisted colonoscopy (CAC).

BACKGROUND: Although colonoscopy is the standard procedure in the diagnosis of colorectal neoplasia, a significant number of clinical relevant lesions may be missed even by experienced endoscopists using current technology. A transparent cap mounted at the tip of a colonoscope may be an easy way to extend the visual field during colonoscopy and may improve the detection rate of mucosal lesions. MATERIAL AND METHODS: The significance of cap assisted (CAC) vs. conventional colonoscopy (CC) on polyp detection rate was evaluated in a prospective randomized controlled trial in 504 patients. RESULTS: CC and CAC detected polyps in 39.3 % and 31.8, not significantly different. There was also no significant difference between CAC and CC according to age, sex, indication for colonoscopy, diverticulosis, sedation, bowel cleansing, withdrawal time, time/number of attempts to intubate the cecal walve, number, localization, size or histology of polyps,. However, the time to reach the cecal floor and the overall time of colonoscopy were significantly lower for CAC (1 minute). CONCLUSION: CAC was without clinical impact on polyp detection rate or performance of colonoscopy.

Sedation-associated complications in endoscopy--prospective multicentre survey of 191142 patients.

BACKGROUND/AIMS: Propofol sedation is applied as moderate sedation for almost all diagnostic and interventional endoscopies. Propofol sedation bears the risk of complications such as respiratory as well as cardiopulmonary insufficiency including sedation-induced death. According to recent guidelines, non-anesthesiologist-administered propofol (NAAP) should be performed by an additional person who has NAAP as their sole task. METHODS: In a prospective multicentre survey involving 191,142 patients, clinically relevant endoscopy-associated complications were registered from 02/2010 to 01/2012. RESULTS: The majority of propofol sedations were applied without additional persons for NAAP. Overall endoscopy-related complication rate was 0.0022 % (n = 424) and sedation-related complications 0.00 042 % (n = 82). Variability over time and between the clinics was low and not influenced by the number of endoscopies performed during the investigation period. Sedation-related death occurred in 6 patients (0.00 003 %), 50 % during emergency endoscopies. In all sedation-associated deaths the patients had ASA class 3 before endoscopy. All fatal complications occurred in the presence of an additional trained person for NAAP. CONCLUSION: This large prospective survey shows that propofol sedation in gastrointestinal endoscopy is a safe procedure with a low potential of risk in daily routine. However, high risk patients (ASA ≥ 3) should be identified, especially before emergency endoscopies and managed by additional persons for NAAP and under intensive care surveillance.

[How safe is sedation in gastrointestinal endoscopy? A multicentre analysis of 388,404 endoscopies and analysis of data from prospective registries of complications managed by members of the Working Group of Leading Hospital Gastroenterologists (ALGK)]. / Wie sicher ist die Sedierung in der gastrointestinalen Endoskopie? Eine multizentrische Auswertung von 388 404 Endoskopien und Auswertung der Daten aus prospektiv geführten Komplikationsregistern von Mitgliedern der Arbeitsgemeinschaft leitender Gastroenterologen im Krankenhaus (ALGK).

BACKGROUND: Gastrointestinal endoscopies are increasingly being carried out with sedation. All of the drugs used for sedation are associated with a certain risk of complications. Data currently available on sedation-associated morbidity and mortality rates are limited and in most cases have substantial methodological limitations. The aim of this study was to record severe sedation-associated complications in a large number of gastrointestinal endoscopies. METHODS: Data on severe sedation-associated complications were collected on a multicentre basis from prospectively recorded registries of complications in the participating hospitals (median documentation period 27 months, range 9 - 129 months). RESULTS: Data for 388,404 endoscopies from 15 departments were included in the study. Severe sedation-associated complications occurred in 57 patients (0.01 %). Forty-one percent of the complications and 50 % of all complications with a fatal outcome (10/20 patients) occurred during emergency endoscopies. In addition, it was found that 95 % of the complications and 100 % of all fatal complications affected patients in ASA class ≥ 3. CONCLUSIONS: Including nearly 400,000 endoscopies, this study represents the largest prospective, multicenter record of the complications of sedation worldwide. The analysis shows that sedation is carried out safely in gastrointestinal endoscopy. The morbidity and mortality rates are much lower than previously reported in the literature in similar groups of patients. Risk factors for the occurrence of serious complications include emergency examinations and patients in ASA class ≥ 3.

[Diagnosis of oesophageal reflux by PH, impedance, and bilirubin measurement: recommendations of the German Society of Neurogastroenterology and of the working group for neurogastroenterology of the German Society for Digestive and Metabolic Diseases]. / Ösophageale Refluxdiagnostik - pH-Metrie, Impedanzmessung, Bilirubin-Messung: Empfehlungen der Deutschen Gesellschaft für Neurogastroenterologie und Motilität und der Arbeitsgruppe Neurogastroenterologie der Deutschen Gesellschaft für Verdauungs- und Stoffwechselkrankheiten.

The current recommendations on indications, technical performance, and interpretation of diagnostic techniques for oesophageal reflux update the German recommandations about 24 hour pH measurement of 2003. The recommendations encompass conventional pH measurement, wireless pH measurement, pH and impedance measurements, and bilirubin measurement (duodenogastro-oesophageal reflux).

Cap-assisted colonoscopy (CAC) significantly extends visualization in the right colon.

BACKGROUND: Although colonoscopy is the standard procedure in the diagnosis of colorectal neoplasia, a significant number of clinically relevant lesions may be missed even by experienced endoscopists using current technology. Particular problems may occur with blind spots behind the semilunar folds and within the right colon. A transparent cap mounted at the tip of a colonoscope may be an easy way to extend the visual field during colonoscopy and may improve the detection rate of mucosal lesions. However, data in the literature are controversial and the quantity of the potential extension of visualization by a transparent cap has not been reported yet. MATERIAL AND METHODS: The significance of cap-assisted colonoscopy (CAC) to increase visualization within different colonic segments (rectum, sigmoid colon, descending colon, transverse colon, ascending colon, cecum) was quantitatively analyzed by randomized back-to-back colonoscopies with and without cap. The investigations were performed in a colonic training model by 5 investigators. The inner colonic surface was stained by a raster of dots and the number of dots counted during colonoscopy served as a measure for the visible surface area of each segment. RESULTS: The time to advance the colonoscope to the respective colonic segments and the overall time to reach the cecum were not significantly different between conventional and CAC. In contrast, overall withdrawal time and withdrawal times for the cecum, ascending colon, descending colon and rectum were significantly longer for CAC, but not for the transverse and sigmoid colon. Visualization of the colonic surface was significantly increased during CAC. Overall, 59.76 ± 2.70 % of the maximal countable dots were visualized without cap and 85.36 ± 9.62 % with cap. The improvement of visualization was only significant for the right colon, but not for the rectum, sigmoid or descending colon. CONCLUSION: The finding of the present study suggests that the extension of visualization by CAC may be of particular value for the right colon.

Fructose malabsorption: how much fructose can a healthy subject tolerate?

BACKGROUND/AIMS: In a prospective study, we evaluated fructose absorption capacity in 17 healthy female volunteers aged 16-27 years. METHODS: All volunteers underwent analysis of their daily food intake diary and standardized breath tests. The volunteers were challenged consecutively with oral intake of 50, 25 and 15 g of fructose. RESULTS: The average daily ingestion of fructose (19.54 ± 14.95 g) was not different between volunteers with positive and negative breath tests. On day 1, 53% of subjects exhibited a significant (≥20 ppm) increase in breath hydrogen and gastrointestinal symptoms upon challenge with 50 g of fructose. Moreover, 37.5% of the volunteers with a negative breath test became positive upon a second challenge with 50 g of fructose but remained asymptomatic. On day 2, 1 of the 9 volunteers (12.5%) with a positive breath test on day 1 exhibited an asymptomatic positive breath test upon exposure to 25 and 15 g of fructose on day 3. The 8 volunteers with a negative test (25 g of fructose) remained negative after a second exposure to 25 g of fructose. CONCLUSION: The results of this study indicate that hydrogen breath tests with fructose challenge of 50 g of fructose are inappropriate to characterize clinically significant fructose malabsorption.

[Endoscopic therapy for leaks in the gastrointestinal tract, the bile ducts and the pancreas]. / Endoskopische Therapie von Leckagen im Gastrointestinaltrakt, an den Gallenwegen und im Pankreas.

Surgery has been the mainstay of therapy in patients with gastrointestinal perforations, leakage or fistulas. New techniques for endoscopic closure of gastrointestinal perforations provide tools for an effective treatment by less invasive procedures. Temporary placement of covered self-expanding stents is an established therapy for oesophageal perforations and anastomotic leaks. Using conventional endoclips small perforations and leaks in the oesophagus and gastrointestinal tract may be closed. With the new over-the-scope-clips a more effective endoscopic full wall closure is possible in the upper gastrointestinal tract and the rectum. Endoscopically guided endoluminal vacuum therapy using polyurethane sponges is an established method for treating rectal leaks and is now increasingly used also in oesophageal leaks. Biliary leakage following endoscopic or surgical interventions is effectively treated with temporary bile stenting in most cases, but closure using metal stents or coiling may be necessary. Pancreatic leaks are a major therapeutic problem and may require multimodal therapies.

Evidence for mast cell activation in patients with therapy-resistant irritable bowel syndrome.

Previous findings suggested an involvement of mast cells in the pathogenesis of irritable bowel syndrome (IBS). The pathophysiological significance of mast cells is defined both by their number in tissue and by their activity. In the present pilot study activity of mast cells in patients with therapy-resistant IBS was investigated for the first time systematically. Twenty patients with therapy-resistant IBS were investigated for the presence of a pathologically increased mast cell mediator release by means of a validated structured interview suitable to identify mast cell mediator-related symptoms and by determing selected surrogate parameters for mast cell activity. Nineteen of the 20 patients presented mast cell mediator-related symptoms. Pathologically increased mast cell activity-related coagulation and fibrinolysis parameters were detected in 11 of 12 patients investigated in that regard. One patient had an elevated level of methylhistamine in urine. The present data provide evidence that in patients with therapy-resistant IBS a pathologically increased systemic mast cell activity may occur with high prevalence. This finding fits to the idea of an assumed contribution of activated mast cells in the pathophysiology of IBS.