[Whether or not to perform an early endoscopy following ingestion of potentially caustic agents - a retrospective longterm analysis in a tertiary referral institution]. / Wann sollte eine frühe endoskopische Inspektion bei Verletzungen des oberen Gastrointestinaltrakts nach Ingestion von potenziell ätzenden Substanzen und anderen Noxen erfolgen? - Eine retrospektive 13-Jahres-Analyse in einem tertiären Haus der Maximalversorgung.

BACKGROUND: The optimal clinical management of patients following ingestion of potentially caustic lesions is still undetermined. In particular, the indication for early upper GI endoscopy in this context remains unclear. PURPOSE: To draft recommendations regarding the use of early upper GI endoscopy following hospital admissions of patients after ingestion of potentially caustic agents. METHODS: For this purpose, a retrospective cohort study of patients treated for ingestion of potentially caustic substances during a 13 year-period at the university hospital of Berne was performed. RESULTS: In total, 61 patients with acute ingestion of potentially caustic substances were identified. Overall mortality was 5 %. 11/61 patients had to be admitted to the intensive care unit. Most ingestions were performed in suicidal intention (62 %). In 53 % of these patients, a combined ingestion of several substances occurred. In 33 % of patients, an early upper GI endoscopy was performed within 24 hours after ingestion. The degree of burn depended upon the hazard potential of the respective substance. In patients with ingestion of low risk substances, upper GI endoscopy was only performed when additional risk factors were present. CONCLUSION: Based upon the results of the present study, ingestion of potentially caustic agents requires an individualized strategy whether or not to perform early endoscopy.

The effect of naloxone-3-glucuronide on colonic transit time in healthy men after acute morphine administration: a placebo-controlled double-blinded crossover preclinical volunteer study.

BACKGROUND: Constipation is a significant side effect of opioid therapy. We have previously demonstrated that naloxone-3-glucuronide (NX3G) antagonizes the motility-lowering-effect of morphine in the rat colon. AIM: To find out whether oral NX3G is able to reduce the morphine-induced delay in colonic transit time (CTT) without being absorbed and influencing the analgesic effect. METHODS: Fifteen male volunteers were included. Pharmacokinetics: after oral administration of 0.16 mg/kg NX3G, blood samples were collected over a 6-h period. Pharmacodynamics: NX3G or placebo was then given at the start time and every 4 h thereafter. Morphine (0.05 mg/kg) or placebo was injected s.c. 2 h after starting and thereafter every 6 h for 24 h. CTT was measured over a 48-h period by scintigraphy. Pressure pain threshold tests were performed. RESULTS: Neither NX3G nor naloxone was detected in the venous blood. The slowest transit time was observed during the morphine phase, which was significantly different from morphine with NX3G and placebo. The pain perception was not significantly influenced by NX3G. CONCLUSIONS: Orally administered NX3G is able to reverse the morphine-induced delay of CTT in humans without being detected in peripheral blood samples. Therefore, NX3G may improve symptoms of constipation in-patients using opioid medication without affecting opioid-analgesic effects.

Esophageal strictures in adult eosinophilic esophagitis: dilation is an effective and safe alternative after failure of topical corticosteroids.

Strictures are a frequent complication of eosinophilic esophagitis. The efficacy and safety of topical corticosteroids and of dilation of eosinophilic esophagitis-associated strictures have not yet been thoroughly clarified. We present a retrospective analysis of 10 adult patients with eosinophilic esophagitis who had symptomatic esophageal stenosis that was unresponsive to topical corticosteroids, and who were treated using bougienage. Eight patients had one single stricture, one patient had two, and another had three strictures; mean stricture length was 2.1 cm (range 1 - 6 cm). Bougienage led to prompt symptom relief. Apart from transient postprocedural odynophagia, no severe complications occurred. During the follow-up (mean 6 months; range 2 - 11 months), all patients enjoyed sustained treatment response.

[The hepato-pulmonary syndrome--where do we stand in the year 2006?]. / Das hepatopulmonale Syndrom -- Wo stehen wir im Jahr 2006?

The hepato-pulmonary syndrome (HPS) is characterized by a combination of liver disease and pulmonary gas exchange abnormalities with arterial hypoxemia, intrapulmonary vasodilatation and arteriovenous shunting in the absence of intrinsic cardiopulmonary disease. The course of the disease is typically progressive. The mortality rate correlates with the pulmonary shunt volume and the degree of hypoxemia at room air. While the patho-physiology of HPS is still not fully understood, a multifactorial etiology is favored. Apart from functional intrapulmonary arteriovenous shunts which appear to represent a major factor in the development of HPS, both ventilation-perfusion mismatch and limited oxygen diffusion contribute to the HPS. Regarding its clinical appearance, pulmonary and hepatic symptoms have to be distinguished. Contrast echocardiography is the primary diagnostic tool. Symptomatically, hypoxemia can be treated with oxygen. So far, the only successful treatment approach which has been tested in larger patient groups, is liver transplantation. Given this background, the aim of this review is to critically discuss current concepts of this serious complication of liver diseases.

[Abdominal pain]. / Abdominaler Schmerz.

Abdominal pain can result from a variety of different intra- and extra-abdominal disorders. Given the wide variety of etiological triggers for this pain, the primary task during the first stage of the diagnostic work-up is to determine as soon as possible the underlying cause and the degree of emergency. The aim of this evaluation is to adapt the therapeutic measures which are necessary for a causal treatment to the individual situation. Contrary to somatic causes of abdominal pain, the availability of such a causal therapy for functional bowel disorders is still very limited. Given this dilemma, the therapeutic focus of abdominal pain associated with these functional syndromes has to be placed on symptom-oriented treatment.

Human ileal bile acid transporter gene ASBT (SLC10A2) is transactivated by the glucocorticoid receptor.

BACKGROUND: Patients with Crohn's disease suffer from intestinal bile acid malabsorption. Intestinal bile acid absorption is mediated by the apical sodium dependent bile acid transporter ASBT/IBAT (SLC10A2). In rats, ASBT is induced by glucocorticoids. AIMS: To study whether human ASBT is activated by glucocorticoids and to elucidate the mechanism of regulation. PATIENTS AND METHODS: ASBT expression in ileal biopsies from patients with Crohn's disease and from healthy subjects was quantified by western blot. ASBT promoter function was studied in luciferase assays and by electrophoretic mobility shift assay. RESULTS: In 16 patients with Crohn's disease, ASBT expression was reduced to 69 (7.5)% compared with healthy controls (mean (SEM); p = 0.01). In 10 healthy male volunteers, ASBT protein expression was increased 1.34 (0.11)-fold (mean (SEM); p<0.05) after 21 days' intake of budesonide (9 mg/day) whereas expression of the peptide transporter 1 was unaffected. Reporter constructs of the human ASBT promoter were activated 15-20-fold by coexpression of the glucocorticoid receptor (GR) and exposure to the GR ligands dexamethasone or budesonide. Two glucocorticoid response elements in the ASBT promoter, arranged as inverted hexanucleotide repeats (IR3 elements), conferred inducibility by GR and dexamethasone in a heterologous promoter context and were shown to bind GR in mobility shift assays. CONCLUSIONS: Human ASBT is induced by glucocorticoids in vitro and in vivo. Induction of ASBT by glucocorticoids could be beneficial in patients with Crohn's disease who exhibit reduced ASBT expression. This study identifies ASBT as a novel target of glucocorticoid controlled gene regulation in the human intestine.

Dysphagia in Crohn's disease: a diagnostic challenge.

Dysphagia is a rare manifestation in a patient with Crohn's disease. We report on the case of a patient with long-standing Crohn's disease who developed progressive dysphagia over 3 years. Endoscopy showed minimal distal oesophagitis with non-specific histological findings. Further investigation with cinematography, barium swallow and manometry established an achalasia-like motility disorder. Biopsies obtained from the oesophagus were non-specific. Balloon dilatation was performed. Initial success was followed by recurrent dysphagia. At repeat endoscopy, an oesophageal fistula was detected. An attempt at conservative medical management failed and oesophagectomy was successfully performed. Pathology results of the resected specimen confirmed the suspected diagnosis of oesophageal Crohn's disease. Even if achalasia is suspected in a Crohn's patient, it should be taken into consideration that the motility disorder could be the result of a transmural inflammation with or without fibrosis caused by Crohn's disease.

Influence of naloxone on gastric emptying of solid meals, myoelectrical gastric activity and blood hormone levels in young healthy volunteers.

There is considerable evidence that opioid mechanisms are involved in the mediation of pyloric motor responses that in turn regulate gastric emptying. The purpose of this randomized, placebo-controlled crossover study was to investigate the effect of naloxone on gastric emptying of a solid meal, gastric myoelectrical activity and the postprandial release of gastrointestinal peptides and neuropeptides in 20 healthy volunteers. Naloxone was administered as an intravenous bolus, followed by continuous infusion according to an intravenous dosing nomogram. Gastric emptying time was evaluated by scintigraphy and gastric myoelectrical activity was evaluated by cutaneous electrogastrography. Naloxone did not significantly alter gastric half-emptying time and postprandial dominant gastric electrical frequency compared with placebo. It also did not significantly change the plasma levels of several peptide hormones with the exception of neuropeptide Y, which was significantly increased (P = 0.001). In conclusion, in doses that influence human intestinal motility, naloxone had no effect on gastric motility and release of several peptide hormones in healthy male volunteers. The importance of the isolated increased neuropeptide Y plasma level needs further investigation.

Does intravenous ondansetron affect gastric emptying of a solid meal, gastric electrical activity or blood hormone levels in healthy volunteers?

BACKGROUND: In previous studies, tropisetron has been shown to accelerate gastric emptying of a solid meal. However, it is uncertain whether other specific 5-hydroxytryptamine-3 receptor antagonists, such as ondansetron, also have a gastroprokinetic effect in humans. AIM: To evaluate the effect of ondansetron on gastric half-emptying time (T1/2) of a solid meal, gastric myoelectrical activity and hormone levels in 14 healthy volunteers. METHODS: In a placebo-controlled, randomized, crossover study, we investigated the effects of ondansetron (8 mg intravenously) on the gastric emptying of solids (by scintigraphy), gastric myoelectrical activity (by electrogastrography) and the post-prandial release of cholecystokinin, gastrin, human pancreatic polypeptide, gastric inhibitory polypeptide, vasoactive intestinal polypeptide, motilin, substance P and galanin. RESULTS: The average T1/2 values were 86 min and 85.5 min without lag time (P=0.082) and 92 min and 93 min with lag time (P=0.158) for the placebo and ondansetron treatments, respectively. The average T1/2 of female volunteers was significantly longer than that of male volunteers. The dominant gastric electrical frequency and hormone plasma concentrations were not altered by ondansetron. CONCLUSIONS: Ondansetron did not affect the gastric emptying of solids, the dominant gastric electrical frequency or the plasma concentrations of the analysed gastrointestinal peptides.

Acute pancreatitis--ERCP/endoscopic papillotomy (EPT) yes or no?

Until the mid eighties ERCP and EPT were considered to be contraindicated in acute pancreatitis, because of possible aggravation of active pancreatitis or induction of new attacks of pancreatitis. This attitude was revised with the new knowledge obtained from four prospective randomised studies, which compared the effects of endoscopic treatment with conservative management of acute pancreatitis. Although the four studies are not strictly comparable their results indicate that there is no advantage to ERCP +/- EPT over conservative treatment alone in mild biliary pancreatitis. In severe biliary pancreatitis, however, ERCP with EPT reduced the number of purulent cholangitis and incidence of morbidity and in one study mortality was also significantly reduced. There is evidence, that ERCP + EPT may be important in a deteriorating acute mild pancreatitis, in the smouldering type of pancreatitis and in pancreatitis with persistent cholostasis. To avoid recurrent severe pancreatitis in patients unfit for surgery without bile duct stones but with gallbladder stones, EPT is recommended. ERCP and EPT in acute severe biliary pancreatitis during the first trimester of pregnancy have been successfully performed in four patients. Sludge and microlithiasis may be the cause of recurrent "idiopathic" pancreatitis and ERCP + EPT is effective especially in cholecystectomised patients. Furthermore in patients with recurrent pancreatitis due to malformations, such as pancreas divisum, ERP and minor-papillotomy produced similar results to surgical treatment. Acute pancreatitis in patients with pancreatic duct stones or ductal leaks may be treated by ERP and EPT in selected patients. Alcoholic, metabolic and infectious pancreatitis remain within the domain of conservative treatment.

Impacted papilla minor stone in pancreas divisum causing severe acute pancreatitis: a case for early ERCP in acute pancreatitis of unknown origin.

This is the first description of severe acute pancreatitis in pancreas divisum caused by a solitary stone impacted in the minor papilla. Recovery was rapid after diagnostic endoscopic retrograde cholangiopancreaticography (ERCP) and endoscopic stone removal. Since other etiological factors accounting for the acute pancreatitis were carefully excluded, it seems that obstruction of the minor papilla by a solitary pancreatic concrement was the most likely cause of acute pancreatitis. This case report demonstrates the diagnostic importance of early ERCP in cases of etiologically unexplained acute pancreatitis.

[Idiopathic dilatation of the large intestine (Ogilvie syndrome--acute pseudo-obstruction)]. / Idiopathische Dickdarmdilatation ("Ogilvie-Syndrom"--"Akute Pseudoobstruktion").

Acute colonic pseudo-obstruction (Ogilvie's syndrome) is characterized by abdominal distention and massive colonic dilatation without any mechanical cause of obstruction. We have reviewed the records of 57 patients, 36 men and 21 women (median age 65.4 y), from 1/1992 to 12/1996, with a colonic pseudo-obstruction, defined as dilatation of at least 10 cm on plain abdominal x-ray. 38 cases (66.5%) followed surgery or trauma and 19 (33.5%) developed symptoms during severe medical illness. 36 cases (63.2%) got i.v. narcotics prior to development of Ogilvie's syndrome. 4 patients underwent conservative treatment alone, 53 patients (93%) had endoscopic decompression with a decompression tube placed in 49 (86%). Due to 2 failures and 2 complications of endoscopic treatment (one ischemic lesion, one perforation; complication rate 3.8%) 4/53 patients had to be operated (7.5%). Clinical success of endoscopic treatment was 88.6% at first attempt and 92.5% at second attempt. General complications tended to be severe, according to the concomitant diseases (morbidity 35%); overall hospital mortality was 21% (12/57). In conclusion, we believe that endoscopic decompression and tube placement is effective and safe for acute colonic pseudo-obstruction not responding to 24 hour conservative treatment.

[Lower gastrointestinal hemorrhage: etiologic assessment and surgical concept]. / Untere gastrointestinale Blutung: Abklärungsstrategie und Operationskonzept.

Due to its occurence in patients at higher ages with comorbidities, lower gastrointestinal bleeding remains a challenge in terms of diagnostic and therapeutic strategies. In this series (1994-1997, n = 40) the source of bleeding was in the upper gastrointestinal tract in 38% and in the lower gastrointestinal tract in 62%. The source of bleeding could be localized in 58%. Bleeding stopped spontaneously in 40% of all patients but 60% required intervention (54% radiologic or endoscopic intervention, 46% surgery). Segmental resection was the procedure most frequently employed (8/11 patients), 3 patients underwent a subtotal colectomy. In-hospital mortality and surgical morbidity were 0/11 each. Following a staged diagnostic approach and segmental surgical resection, lower gastrointestinal bleeding can be treated with a low morbidity, mortality and a low rebleeding rate.

Comparison between esophageal Wallstent and Ultraflex stents in the treatment of malignant stenoses of the esophagus and cardia.

BACKGROUND AND STUDY AIMS: Several published studies have examined various self-expanding metal esophageal stents for use in the palliative treatment of esophageal or cardiac neoplasia, but few have compared different self-expanding metal stents. The aim of this study was to evaluate non-covered Wallstent and Ultraflex prostheses in the treatment of malignancies in the esophagus and the cardiac region. MATERIALS AND METHODS: In a retrospective study, the effectiveness of non-covered Wallstents (46 patients) and Ultraflex stents (36 patients) was compared in the treatment of malignancies in the esophageal and cardiac regions. RESULTS: Reintervention procedures were necessary in 16 of the 46 Wallstent patients (six patients during an early phase) and in 22 of the 36 Ultraflex patients (13 during an early phase) (overall P = 0.022; early P = 0.018). The major complication in the Wallstent group was tumor ingrowth (12 of 35 complications), while in the Ultraflex group, it was incomplete deployment (18 of 49 complications). Incomplete stent deployment occurred more often in patients treated with Ultraflex (P = 0.01), and food impaction was more often observed in the Wallstent group (P = 0.001). In addition, in patients with Ultraflex stents, more complex reinterventions were necessary than those required with Wallstents (four vs. 13 complex reinterventions, P = 0.0046). Wallstents tended to improve dysphagia better than Ultraflex stents. CONCLUSION: Compared to Ultraflex stents, Wallstents have several significant short-term and long-term advantages in the palliative treatment of malignancy of the esophagus and cardia.

Self-expanding metal stents in malignant esophageal obstruction: a comparison between two stent types.

OBJECTIVES: Self-expanding metal stents are a promising alternative in the palliation of malignant esophageal obstruction, but the relative value of different stent types is not well established. METHODS: During a 3-year enrollment period in four different centers, 82 consecutive patients with malignant dysphagia without tumor recurrence after surgery or esophagorespiratory fistulas received either an uncovered Wallstent (44 patients) or a knitted nitinol stent (38 patients). RESULTS: Age (median: 79 yr), sex (F:M = 33:67), dysphagia score (median: 3), Karnofsky score (median: 53), body mass index (median: 19), type of pretreatment, tumor stage, stricture length (median: 5.4 cm), and stricture location were comparable in both stent groups. After stent placement, median dysphagia score improved markedly in both groups by two points. Procedure-related mortality (16 vs 0%; p < 0.01), early complication rate (32 vs 8%; p < 0.01), and severe persistent pain after stent placement (23 vs 0%; p < 0.002) were higher in the Wallstent compared with the knitted nitinol stent group. In contrast, stent dysfunction (7 vs 32%; p < 0.005), reintervention rate (9 vs 34%; p < 0.005), and costs were lower in the Wallstent compared with the nitinol stent group. CONCLUSIONS: In malignant esophageal obstruction, both stents markedly improved dysphagia. Uncovered Wallstents seem to cause more early severe complications than knitted nitinol stents. In contrast, stent dysfunction, reintervention rate, and costs appear to be higher in the nitinol stent group.

[15 years of endoscopic therapy in choledocholithiasis]. / 15 Jahre endoskopische Therapie der Choledocholithiasis.

INTRODUCTION: The relevance of endoscopic retrograde cholangiopancreatography (ERCP) in the diagnosis and treatment of common bile duct stones has increased since the introduction of laparoscopic cholecystectomy in 1989-1990. METHODS: The number, indications, success and complication rate of ERCP were analyzed retrospectively in 1121 consecutive patients with bile duct stones treated at Berne University Hospital between 1980 and 1994. RESULTS: The number of patients undergoing endoscopic stone extraction increased slowly from 1980 to 1990, but has shown a 4-fold increase in the last 5 years parallel to the introduction of laparoscopic cholecystectomy. Failure to diagnose and remove bile duct stones decreased 5-fold from 23% (14 of 60 patients) in 1986 to 4.4% (10 of 225 patients) in 1994. Major complications occurred in 3.2% (30 of 617 patients) and consisted of acute pancreatitis (1.6%), hemorrhage of the papilla (1%), and cholangitis (0.6%). The severity but not the number of complications has decreased in the last 15 years. CONCLUSION: Gallbladder stones with common bile duct stones are usually treated by endoscopic stone extraction combined with laparoscopic cholecystectomy. Open operation with bile duct exploration is reserved for a small subgroup of patients with specific problems.

[Pancreatic carcinoma: diagnosis]. / Pankreaskarzinom: Diagnostik.

Early detection, tumor diagnosis with histological proof and tumor-staging are the principle aims of diagnostic approaches in patients suffering from pancreatic cancer. Asymptomatic and small cancers are often missed since they produce no or no typical symptoms and no reliable screening methods are available. Symptomatic pancreatic cancers are often so advanced that only about 20-30% of patients qualify for curative treatment. The diagnosis of pancreatic cancer with histological characterization occurs by imaging techniques [sonography and CT-scan with guided fine needle punction, MRI, ERCP with biopsy or aspiration cytology, endoscopic sonography] and in some cases by laparoscopy or laparotomy. The combined use of tumor markers [CA 19-9, CEA, elastase-1] support the diagnosis of pancreatic cancer. The same methods used for diagnosis are also used for the preoperative tumor staging. Unfortunately the accuracy of these methods is smaller than 77%. The involvement of lymph nodes, encasement of large vessels and small liver metastases or a peritoneal spread of the tumor may be difficult to visualize and the real extent of the disease may only be observed during laparotomy.

Wallstents versus plastic stents in malignant biliary obstruction: effects of stent patency of the first and second stent on patient compliance and survival.

OBJECTIVES: In prospective trials in patients with malignant biliary obstruction, it has been reported that Wallstents prolong stent patency, but this does not translate into a significant survival benefit. Compared with prospective trials, however, survival may be different in clinical practice because of differences in patient compliance. We report on a retrospective, long term analysis comparing Wallstents versus plastic stents. METHODS: Plastic endoprostheses (70 patients) and endoscopic Wallstents (95 patients) were placed in 165 consecutive patients with irresectable, malignant biliary obstruction in a first (1990-91) and second (1992-93) time period. Stent occlusion was treated by plastic stent placement. RESULTS: Patient characteristics were quite comparable in both stent groups. Initial placement of a Wallstent resulted in an increase of median stent patency of the first (10 vs 4 months, p < 0.001) and second (8 vs 3 months, p < 0.05) stent, a decrease of additional endoscopic procedures (20 vs 58%, p < 0.005), an increase of patient compliance reflected by a decrease of patients dying with untreated stent occlusion (9 vs 30%, p < 0.001), and an increase of survival time (6.5 vs 4 months, p < 0.05). CONCLUSIONS: Initial placement of a Wallstent results in an increase of stent patency of the first and second stent. Duration of stent patency appears to have a determinant effect on patient compliance. Increased stent patency and patient compliance seem to improve survival in clinical practice.