Replacement of conventional glucocorticoids by oral pH-modified release budesonide in active and inactive Crohn's disease: results of an open, prospective, multicenter trial.

Glucocorticosteroids (GCS) are established in the treatment of active Crohn's ileitis and ileocolitis. Recently, the topical steroid budesonide was found to be effective in untreated patients with Crohn's disease (CD) causing less side effects than conventional GCS. No clinical data have been reported about the effects of switching from conventional GCS to budesonide in terms of side effects and disease activity. The primary aim of this study was to evaluate the development of side effects after switching from conventional GCS treatment to Eudragit L-coated budesonide (pH-modified release formulation) in patients taking 5-30 mg prednisolone equivalent per day for at least two weeks. In all, 178 patients with active CD (N = 88) or CD in remission during GCS treatment (N = 90) were included. Conventional GCS treatment was tapered down during a maximum of three weeks, with simultaneous intake of 3 x 3 mg budesonide. Thereafter, patients received 3 x 3 mg budesonide alone for six weeks. GCS-related side effects, disease activity and adverse events were documented at study entry and after 0, 2, 4, and 6 weeks of budesonide treatment. The percentage of patients with GCS-related side effects decreased from 65.2% (intention-to-treat-population) at entry to 43.3% (P < 0.0001) at the end of the trial. The total number of GCS-related side effects decreased significantly from 269 to 90. Of the patients who entered the study with active disease under conventional GCS therapy, 38.6% were in remission at the end of the study. Of the patients who entered the study with CD in remission, 78% stayed in remission after switching from conventinal GCS to budesonide. In conclusion, switching from conventional GCS treatment to budesonide leads to a significant reduction of GCS related side effects in patients with CD without causing rapid deterioration of the disease.

[Paraneoplastic spastic tetraparesis in glucagonoma syndrome. Successful therapy with octreotide, dacarbazine and interferon-alpha]. / Paraneoplastische spastische Tetraparese bei Glukagonomsyndrom. Erfolgreiche Therapie mit Octreotid, Dacarbazin und Interferon-alpha.

Within four years a 44-year-old man developed a glucagonorma syndrome with insulin dependent diabetes mellitus, weight loss, diarrhea, anemia and a marked superinfected eczema. He developed an organo-cerebral psychosyndrome with cognitive retardation and syncoptic disturbance of consciousness, followed by a tetraspasticity with tetraparesis, micturition difficulties and fecal incontinence. There were a general cerebral atrophy as verified by means of MRT and signs of a demyelinating cerebral disease. The plasma concentration of glucagon was 48 fold elevated to 8,536 ng/l. By means of ultrasonography, CT, ERCP, and angiography a tumorous mass of the corpus and tail of the pancreas, 61 x 32 mm in size, was found with signs of infiltration into the region of the aorta and the splenic vein. Furthermore the liver showed diffuse partially cystic metastases. The diagnosis was certified by fine needle biopsy and histologic examination with Grimelius straining. A thrombosis of the femoral vein was detected by CT. The patient was treated by a debulking resection of the corpus and cauda of the pancreas combined with splenectomy and a drug therapy using octreotide. All paraneoplastic symptoms could be widely reduced. Plasma glucagon concentration decreased from 2,200 ng/l to 600 ng/l. Because of a liver enlargement due to the growth of metastases he was successfully treated with dacarbazine 250 mg/m2 per day during six monthly cycles for five days and interferon-alpha 3 x 3 millions units per week for six months followed by a normalization of the liver volumen.

[Inflammatory pseudotumor of the liver. Case report of a rare differential diagnosis of hepatocellular carcinoma]. / Inflammatorischer Pseudotumor der Leber. Fallbericht über die seltene Differentialdiagnose des hepatozellulären Karzinoms.

A 46-year old man suffered from fever, sweating, vomiting, abdominal pains, and watery diarrhea during two weeks. The abdomen was tender on pressure. Laboratory findings revealed increased leucocytes to 18,500/microliters, increased thrombocytes to 513,000/microliters, an increased sedimentation rate of 105/129 mm, CRP of 18.2 mg/dl and slightly elevated activities of the amino-transferases. Ultrasonography showed a tumor of the liver with a diameter of 10 cm and a echocomplex wheel-spoke structure. The tumor was confirmed by computed tomography, nuclear resonance tomography, angiography, and scintigraphy without signs of malignity. Fine needle biopsy was negative. Bisegment resection of the liver revealed a tumor of the liver with focal necrosis, with the histological aspect of fibrous tissue with lymphoid infiltration and multiple abscesses. The diagnosis was "inflammatory pseudotumor of the liver" (IPT). Postoperatively the follow-up half a year later was normal. The IPT ist an important differential diagnosis of the hepatocellular carcinoma. The review of 80 cases shows that operative resection of the tumor is the treatment of choice, because the benign diagnosis cannot maintained without doubts. But the pathognomonic trias of symptoms 1. Inflammatory signs, 2. solid tumor of the liver, 3. normal liver tissue allows to make this exceptional diagnosis. The question is whether the operation of the tumor can be avoided by conservative medical therapy.

[Endosonography with electronic longitudinal scan in malignant diseases of the stomach]. / Endosonographie mit elektronischem Longitudinalscan bei malignen Erkrankungen des Magens.

To assess the significance of endoscopic ultrasonography (EUS) using an electronic longitudinal scan we examined 75 patients. 32 patients suffering from malignant diseases of the stomach (2 early cancers, 22 gastric carcinoma, 4 cancers of the cardia, 2 gastric lymphoma, 2 infiltration from outside). 31 of the 32 patients who had malignant gastric diseases were correctly diagnosed by means of EUS. The positive sensitivity was 96.9%, the positive predictive value was 86.1%. The specificity was 88.4%, the negative predictive value 97.4%. Using sonographical criteria such as thickening of the gastric wall, wall layers, delineation of outer and interior gastric wall, infiltration into the gastric wall, infiltration into neighbouring organs as well as perigastric lymph node, EUS provides reliable determination and staging of gastric tumours. Compared to conventional ultrasonography and gastric endoscopy, EUS affords considerable improvement in the diagnosis of gastric tumours, especially with regard to the identification of the infiltration of the tumour (84.4%), recognition of malignancy (28.1%), identification of the origin of the tumour (21.9%), and of regional lymph node metastases (25%).

[Injection therapy of bleeding peptic ulcer with fibrin or polidocanol]. / Injektionstherapie des blutenden Ulcus pepticum mit Fibrin oder Polidocanol.

The effectiveness of injecting fibrin (group 1; with adrenalin: n = 11; without adrenalin: n = 29) or polidocanol (with [n = 17] or without adrenalin [n = 8]) or adrenalin alone (n = 15) (group 2) in the arrest of bleeding from peptic ulcers was compared in a prospective randomized study of 80 patients (61 males, 19 females; mean age 66.7 [28-92] years). Both groups were comparable regarding age, sex distribution, ulcer site and haemoglobin concentration. The amount of fibrin injected per patient at the first session averaged 2.9 +/- 1.8 ml, that of polidocanol 3.1 +/- 1.9 ml. The initial injection was successful in all but one patients (40 and 39, respectively). Primary definitive haemostasis was achieved in 59 patients (73.8%), with recurrence of bleeding in 20 (9 and 11: 25%). Recurrent bleeding was always treated with fibrin injection. Definitive haemostasis was achieved by a second application of fibrin in eight patients (10%), so that the definitive haemostasis rate was 83.8%. A second recurrence of bleeding was noted in eight patients, requiring surgical treatment. Four patients died during the second recurrence. It is concluded that injection of fibrin is an effective method of treatment of bleeding ulcer. There was no evidence that fibrin was better than polidocanol with or without adrenaline.

Feasibility and effectiveness of a defined-formula diet regimen in treating active Crohn's disease. European Cooperative Crohn's Disease Study III.

In a randomized multicenter trial the efficacy of treatment of active Crohn's disease by means of a liquid defined formula diet (DFD) was tested and compared with a combination of 6-methyl-prednisolone and sulfasalazine. A total of 95 patients participated in the study. By the end of 6 weeks, among 44 patients randomized to drug treatment, 32 showed improvement of the Crohn's disease activity index (CDAI) as compared with 21 of 51 patients receiving oral DFD (p less than 0.05). The proportion of withdrawals in the DFD group (29 of 51) was sevenfold higher than in the drug group (4 of 44). However, most patients (20 of 29) receiving DFD withdrew because of the unpalatability of the liquid diet. Analysis of patients in each group who finished the study showed equal effectiveness of DFD and the drug regimen. In these subsets of patients the CDAI decreased from 280.8 +/- 90.6 to 151.7 +/- 86.5 (DFD) and from 263.7 +/- 86.3 to 129.3 +/- 63.7 (drug), respectively. Improvement of inflammation factors was similar in both groups at the end of the study, although improvement was delayed in the DFD group. In conclusion, our data show a superiority of the drug combination over DFD in the treatment of Crohn's disease under the conditions of this trial. The results do suggest, however, that DFD offers a therapeutic alternative to prednisolone and sulfasalazine in a subgroup of patients, which has to be closer characterized in further studies.

[Sensitization to nickel sulfate in patients with ileitis terminalis (Crohn disease)]. / Sensibilisierung gegen Nickelsulfat bei Patienten mit Ileitis terminalis (Morbus Crohn).

The history of inpatients with Crohn's disease revealed several occurrences of contact dermatitis due to metal ions. Therefore, we considered the question as to whether allergic reactions to amalgam fillings or mercury, delivered in small amounts, could be a factor in the activity of regional enteritis. 23 patients with Crohn's disease (15 females, 8 males), aged from 20 to 44 years were screened by an extended standard patch test (following the rules of the ICDRG). Surprisingly, no case of hypersensitivity to amalgam and/or mercury was found. However, nickelsulfate yielded positive reactions in 39.1% of all tested patients (9/23). In comparison to the normal population this prevalence of nickelsulfate hypersensitivity is distinctly increased. It may be an epiphenomenon of Crohn's disease (sensitization via an enhanced permeability of the irritated mucous membranes for nutritive nickelsulfate) or an etiopathogenetic co-factor. In the latter case regional enteritis might be regarded as an allergic-irritative disease of the bowel.

[Alagille syndrome, a rare differential diagnosis of intrahepatic cholestasis]. / Das Alagille-Syndrom, eine seltene Differentialdiagnose der intrahepatischen Cholestase.

In Alagille's syndrome cholestasis is caused by a congenital hypoplasia of the intrahepatic bile ducts. If cardiac and arterial malformations are present in conjunction with the typical-but not pathognomonic-facies, this rare syndrome must be considered. ERCP shows a highly rarified bile duct system. Liver histology with a paucity of interlobular bile ducts establishes the diagnosis. Inheritance appears to be autosomal dominant. The relatively good prognosis of the disease calls for caution concerning invasive procedures.

[The diameter of arterial and venous abdominal vessels during acute and chronic administration of nitrates. A sonographic study]. / Die Weite von arteriellen und venösen Abdominalgefässen unter akuter und chronischer Gabe von Nitraten. Eine sonographische Untersuchung.

Fourteen male patients with coronary heart disease were randomly assigned to treatment periods with isosorbide dinitrate (ISDN) 120 mg/day (6 X 20 mg) and placebo for 4 weeks each, according to a double-blind protocol with intraindividual cross-over. The luminal diameters of the superior mesenteric artery, the hepatic artery, the superior mesenteric vein and the portal vein were determined sonographically in the supine position on days 1, 14 and 28 of both treatment periods 90 min after drug intake. The measurements were repeated after 1.6 mg sublingual nitroglycerin. On day 1 of drug intake the vessel diameters increased significantly after ISDN as compared to placebo: superior mesenteric artery: +11%; hepatic artery: +26%; superior mesenteric vein: +17%; portal vein: +11% (p less than 0.05). No differences in luminal diameters between both drug regimens were found on days 14 and 28. Additional nitroglycerin caused a marked diameter increase during the placebo period (14-21%; p less than 0.001) and on days 14 and 28 of ISDN therapy, while the drug effects were absent after maximal ISDN-induced vasodilatation on day 1. Thus, nitroglycerin and isosorbide dinitrate administered acutely caused a comparable vasodilatation of arterial and venous vessels in the splanchnic region. During sustained therapy with isosorbide dinitrate the vasodilatory effects of the drug were lost. It is supposed that a decrease of blood pooling in the splanchnic region occurs during sustained ISDN therapy. Despite this tolerance development to the circulatory effects of isosorbide dinitrate, nitroglycerin remained effective with regard to arterial and venous vasodilatation.

Benign lesions of the upper GI tract by means of endoscopic ultrasonography.

In contrast to conventional ultrasound tomography endoscopic ultrasonography (EUS) allows an exact evaluation of the wall of the upper GI tract. The gastric and esophageal walls give a typical five-layer image presumably corresponding to the mucosa (two inner layers), submucosa (middle echogenic layer), muscularis propria (outer echo-poor layer), and serosa (outer echogenic layer). A thickening of the mucosa may be demonstrated in Ménétrier's disease. In patients with gastric antrum ulcers there is considerable thickening of the gastric wall, especially of the submucosa and muscularis. Benign gastric and esophageal submucosal tumors are easily localized between the different layers. They are easily distinguished from malignant processes by means of EUS. In patients with polypoid endoscopic aspect due to an impression from outside, a tumor can be easily excluded.

[Endoscopic ultrasonic study of the esophagus]. / Endoskopische Ultraschalluntersuchung des Osophagus.

Endoscopic ultrasonotomography opens a sonographic window to the organs of the mediastinum. With this technique all segments of the oesophagus can be sonographically investigated. Endosonographic investigations on 11 patients with oesophageal tumors and 3 patients with oesophageal varices showed that the diagnosis of oesophageal carcinoma and differentiation between malignant tumors and benign changes are possible. The spread of the tumor in the horizontal and vertical planes can be accurately determined with endoscopic ultrasonography. In addition, paraoesophageal lymph node metastases, as well as other lesions in the mediastinum, can be diagnosed. Ultrasonography of the oesophagus can be simplified by leaving out the optical system.

Ileal and colonic mucosal bile acids in Crohn's disease and right colonic carcinoma.

Bile acids are supposed to promote colonic cancer. In Crohn's disease, colonic carcinomas are relatively rare. We, therefore, compared ileal and right colonic mucosal bile acids analysed by gas-liquid chromatography in 8 patients with ileal Crohn's disease (14-48 yrs.) and 7 patients with right colonic carcinoma (28-77 yrs.) who underwent surgery. In both ileal and colonic mucosa, nonsulphated bile acid concentrations were somewhat higher in Crohn's disease (20.98 micrograms/g +/- 4.77 SEM; 12.09 micrograms/g +/- 2.55) than in colonic carcinoma (16.06 micrograms/g +/- 3.46; 7.75 micrograms/g +/- 4.28). In ileal mucosa, percentages of lithocholic and deoxycholic acids were slightly higher in colonic carcinoma (3.9%; 23.2%) than in Crohn's disease (1.1%; 14.9%). In colonic mucosa, carcinoma patients had more lithocholic (7.6%) and less deoxycholic acid (11.9%) than patients with Crohn's disease (1.7%; 20.3%). Bile acid sulphate esters were similar in both diseases (ca. 3.0 micrograms/g in ileal, 1.4 micrograms/g in colonic mucosa). Our results show that ileal and right colonic mucosal nonsulphated bile acids tend to be even lower in right colonic carcinoma than in Crohn's disease. This agrees well with our earlier findings of low mucosal bile acid concentrations in patients with left colonic carcinoma (Tokai J Exp Clin Med 8: 59-69, 1983) and does not support the assumption that bile acids are envolved in right colonic carcinogenesis.

[Endosonography using a gastrofiberscope]. / Endosonographie mit einem Gastrofiberskop.

Gastroscopic ultrasound tomography enables a direct sonographic approach to the upper gastrointestinal tract and the surrounding organs. First experiences show that this new method is characterised by a great diagnostic potential. Its advantages compared with conventional sonography are the avoidance of sonographic obstacles and an improved recognisability of details; part of the examined area is, so to say, enlarged due to the use of high ultrasonic frequencies. With an ultrasonic frequency of 7.5 megahertz, the following processes can be visualised more clearly than with conventional sonographic equipment: processes in the pancreas, cholelithiasis of the common bile duct, hepatic foci, processes in the splenorenal angle, as well as tumours of the stomach and of the esophagus. In cardiology, clear indications are easily recognised, such as the atrial septal defect.

Radiological and ultrasonographic investigations with respect to patient selection and monitoring for chemical gallstone dissolution.

786 consecutive patients with suspected gallstones investigated radiologically and ultrasonographically, 231 (33.0%) were found to have stones. Radiological examinations showed that 59.3% of these were suitable for chemical dissolution with cheno- or ursodeoxycholic acid. The percentage of treatable patients fell from age 20 to age 65 from 71% to 48% (p less than 0.05) and then rose again to 61% (not significant). The benefit of litholysis is greater, the earlier it is begun. The results are in disagreement with those of two studies in operated patients. Here only 19-24% were suitable for stone dissolution. Comparative ultrasonographic and radiological studies in 23 patients have shown that monitoring of patients during litholysis can be carried out ultrasonographically. Stone size measured ultrasonographically corresponds sufficiently accurately with that obtained radiographically.

[Ultrasound tomography of the liver and its diseases]. / Ultraschalltomographie der Leber und ihrer Erkrankungen.

The systematical ultrasound investigation of the liver includes parallel sections series as well as vessel oriented sonography. The border between the right and left liver lobe runs through the middle liver vein, through portal and bile duct branchings respectively, and through the gallbladder in a sagittal direction. Liver ultrasound tomography allows differentiation of diseased liver from normal findings as well as subcategorizing into diffuse, focal, vascular, and biliary diseases. The sensitivity for fatty liver and cirrhosis ranges about 80%. The differential diagnosis of different liver diseases by ultrasound tomography will only allow suspected diagnosis. A certain differentiation between benign and malign alteration is only achieved by histological or cytological methods alone. In comparison to other indirect non invasive diagnostical procedures like computerized tomography, scintigraphy and nuclear spin tomography ultrasound tomography appears to be of primary importance.