[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.

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.

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.

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.

[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.

[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.

Pre-, intra- and postoperative staging of gastric carcinoma and clinical outcome.

BACKGROUND: We compared preoperative (combined clinical and radiological staging and endoscopical Borrmann classification), intraoperative (by the surgeon: curative/palliative; R0/R1/R2-resection; intraoperative stage I to IV) and postoperative staging including histological results (pTNM) in respect of resectability and prognosis. METHODS: All patients with adenocarcinoma of the stomach were prospectively and consecutively included in the study protocol and were staged during the hospitalisation by the different specialists. Out of 215 patients with malignant tumors of the stomach, 153 were finally evaluated for the study. We excluded 62 patients with other malignancies or with a follow up of less than 6 months. Preoperative endoscopic Borrmann classification was done by the gastroenterologist, preoperative TNM-classification by the radiologist and surgeon, intraoperative classification by the surgeon and postoperative classification by the pathologist. All results were immediately described in the protocol. Follow-up and survival curves were performed by the Regional Tumor Registry and statistics by the Statistical Department of the University using Kaplan-Meier survival curves and Log-Rank and Wilcoxon Test for significance. RESULTS: Preoperative staging was unreliable and there was no relationship between preoperative and postoperative staging nor survival. In opposite intra- and postoperative staging correlated significantly between the different groups and with survival (p < 0.001). CONCLUSIONS: As long as preoperative staging systems are not improved (which may be in the future the case with endosonography), all operable patients with gastric carcinoma should undergo a laparotomy or laparoscopy, because only intraoperative evaluation of the surgeon allows a decision on a possible curative resection. Patients with stages I-III should be resected radically with complete dissection of lymph node compartments 1 and 2. This policy is justified especially in view of a minimal hospital mortality (3%).

Substance P activates rat colonic motility via excitatory and inhibitory neural pathways and direct action on muscles.

We studied effects of nicotinic, muscarinic, serotoninergic, dopaminergic, adrenergic, vasoactive intestinal peptide (VIP) antagonists, VIP, nitric oxide-synthase inhibitors and stimulators alone and in combination with tetrodotoxin on substance P (SP)-stimulated intraluminal tone of the isolated proximal, middle and distal rat colon. Tetrodotoxin significantly enhanced SP-stimulated intraluminal tonic pressure in the distal, but not in the middle and proximal colon. N omega-nitro-L-arginine methylester enhanced SP stimulation in all colonic segments, whereas L-arginine inhibited it partially and D-arginine did not affect it. Atropine and hexamethonium partially inhibited SP stimulation of the middle and distal colon. Tetrodotoxin completely abolished the effects of L-arginine, atropine and/or hexamethonium on SP stimulation. Propranolol, phentolamine, reserpine, telenzepine, naloxone, Mr 2266, a VIP antagonist (H9935) and ketanserin did not affect SP-induced colonic muscle stimulation. VIP strongly reduced SP-stimulated intraluminal pressure in all colonic segments. VIP(10-28), a putative VIP antagonist, produced similar inhibition of SP-stimulated intraluminal tonic pressure, but did not affect N omega-nitro-L-arginine methylester-induced enhancement of SP-stimulated intraluminal pressure in any segments. It is concluded that in the isolated rat colon SP-stimulated intraluminal pressure (mainly generated by circular muscles) by a direct action on colonic muscles over the whole colonic length and by simultaneous activation of neural cholinergic excitatory pathways in the middle and distal, of noncholinergic excitatory pathways in the proximal colonic segment, and by activation of nitric oxide-dependent inhibitory neural pathways. VIP seems not to be directly involved in this inhibitory pathway.

Comparison of percutaneous and endoscopic retrograde removal of postoperatively retained bile duct stones.

Forty-one patients underwent nonsurgical removal of postoperatively retained bile duct stones in two nonrandomized groups. The endoscopic-retrograde technique was used in 21 patients, and succeeded in 19. The percutaneous approach through the T-tube tract was used in 22 patients, including the two in whom endoscopic stone removal had failed, and was successful in 21 patients. Individual preferences and prior history introduced a selection bias against the percutaneous technique. Auxiliary extracorporeal shockwave lithotripsy (ESWL) was used in 2 patients whose stones could not be fragmented mechanically by the percutaneous basket technique. ESWL was successful in one patient but failed in the second. Because endoscopy had also failed in this case, the patient subsequently underwent repeat surgery. Procedure-related complications were minor with both techniques and were readily treated by conservative measures. We conclude that both the retrograde and the percutaneous approaches are effective and safe. The endoscopic approach appears convenient because there is no need to await maturation of the percutaneous tract, but sphincterotomy carries a small but distinctive risk. Because the percutaneous approach uses an existing tract, is only minimally invasive and leaves the sphincter of Oddi intact, it is preferable in those patients who have T-tubes of appropriate size and position in place.

[12 years of endoscopic stone removal]. / 12 Jahre endoskopische Steinentfernung.

All 583 attempts at endoscopic clearance of biliary calculi, performed in the Gastrointestinal Unit, Inselspital Bern, were retrospectively analyzed from 1980 until 1991. The average age of the patients was 70; 56% were female and 44% male. In 1980, 26 ERCPs for bile duct stone removal were performed, whereas in 1991 the number had increased to 90. The substantial increase in 1991 occurred after introduction of laparoscopic cholecystectomy. Over the total period of 12 years all stones were removed endoscopically after papillotomy in 82%, while the success rate in 1991 was 90%. Morbidity was 5.4% and lethality 0.2%. Total morbidity did not change markedly. However, the number of severe complications requiring surgical repair was reduced from 1.7% between 1980 and 1986 to 0% between 1987 and 1991. These results suggest that endoscopic removal of bile duct stones is increasingly performed with high success and low complication rates.

[Hematemesis. Extramural emergency]. / Hämatemesis. Spital-externer Notfall.

Hematemesis is the cardinal sign of upper gastrointestinal bleeding. It is a sign related to numerous affections, with a prognosis depending on the underlying lesion, the degree of bleeding, the accompanying disease and other risk factors. Mortality rates are generally close to 10%, although if hematemesis is secondary to variceal bleeding, as high as 30%. 65% of hemorrhages subside spontaneously, but 25% bleed recurrently (after initial cessation) and in 10% bleeding persists. Three quarters of all renewed bleeding occurs within two days after the initial hemorrhage. If hematemesis occurs outside a hospital, rapid evaluation is required to assess the necessity of emergency transport and treatment. In the case of severe to moderate bleeding, life-support measures and rapid transport to the nearest hospital are of primary importance and all measures complicating diagnosis and treatment in the hospital should be avoided. Patients with mild hematemesis, stable cardiovascular parameters and no risk factors can be investigated and, if appropriate, treated, on an out-patient basis. If the cause of hematemesis cannot be found, aggressive, inpatient investigations are required at the first sign of second bleed. Endoscopy is the primary investigative procedure for hematemesis. The success rate is highest if endoscopy is performed within the first 36 hours of the onset of bleeding. There are indications that aggressive diagnosis and therapy, including endoscopic hemostatic interventions, can reduce hematemesis mortality.

[Indications for endoscopic papillotomy]. / Indikationen zur endoskopischen Papillotomie.

Endoscopic sphincterotomy (ES) with stone removal is indicated in the post-cholecystectomy patient with retained or recurrent stones and for the very high risk surgical patient. ES has a role in the treatment of severe acute biliary pancreatitis (ABP), but not in mild ABP. Acute suppurative cholangitis refractory to antibiotics can be successfully treated by ES with stone removal or nasobiliary drainage not only in high risk surgical patients. However, concomitant occurrence of abscesses in the liver and other locations, and of gallbladder empyema, calls for an interdisciplinary approach (surgical, endoscopic and radiological). Controlled studies in this field are needed. The role of ES and stone removal in cholelithiasis of patients with gallbladders in situ and low surgical risk remains controversial, as does the treatment of patients with sump syndrome after choledochoduodenostomy, with biliary-cutaneous or biliary-enteric fistulas and benign strictures, which must be evaluated by accurate comparative studies. Whereas ES has its place in the treatment of Oddi sphincter dysfunction with elevated sphincter pressures, and for the introduction of large bore endoprostheses for palliative treatment of malignant biliary stenoses, ES is still experimental in the treatment of pancreatolithiasis, pancreatic duct stenoses, endoscopic gallbladder stone removal and transpapillary retrograde cholangioscopy.