Comparison of two PEG-interferon alpha-2b doses (1.0 or 1.5 microg/kg) combined with ribavirin in interferon-naïve patients with chronic hepatitis C and up to moderate fibrosis.

Health regulatory approval of the 1.5 microg/kg body weight dose of pegylated interferon (PEG-I) alpha-2b in combination with ribavirin for the treatment of chronic hepatitis C was based on a study using PEG-I alpha-2b at doses of only 0.5 and 1.5 microg/kg body weight (BW), in spite of the previously shown flat dose-response curve at doses of > or =1.0 microg/kg. Our aim was to compare PEG-I alpha-2b 1.0 microg/kg with 1.5 microg/kg, both in combination with ribavirin. Open-label, randomized study in 227 patients with biopsy-proven chronic hepatitis C (Metavir < or =F2), receiving oral ribavirin (400 mg, twice daily) in combination with subcutaneous PEG-I alpha-2b (1.0 or 1.5 microg/kg, once weekly) for 24 weeks (genotype 2 or 3), or 48 weeks (other genotypes), followed by a 24-week drug-free period. Virologic response rates did not differ between the two doses of PEG-I alpha-2b: in patients infected with hepatitis C virus (HCV) genotype 1 or 4 treated with PEG-I 1.0 microg/kg BW, 38% (22/58) had a sustained virologic response compared with 39% (27/70) in the PEG-I 1.5 microg/kg BW dose group (P = ns). The corresponding values in patients infected with HCV genotype 2 or 3 were 71% (39/55) and 81% (29/36) respectively (P = ns). Adverse events led to transient or permanent dose reductions in fewer patients in the 1.0 microg/kg BW dose group (48/113 patients; 42%) than in the 1.5 microg/kg BW dose group (63/106 patients; 59%, P = 0.015). Furthermore, 89% of patients treated for 24 weeks but only 58% of patients treated for 48 weeks (P < 0.001) tolerated the treatment without relevant dose reduction or premature termination. In combination with ribavirin, PEG-I alpha-2b 1.0 microg/kg was as effective as 1.5 microg/kg but was better tolerated in patients with chronic hepatitis C and up to moderate fibrosis.

[Esophageal and intestinal stents]. / Osophagus- und Darmstents.

Implantation of expandable metal stents has evolved during the last decade as an established method for the palliation of tumourous obstruction within the gastrointestinal tract. Rigid plastic stents have initially been used for the treatment of dysphagia due to esophageal carcinoma. The development of different types of self expandable metal stents with differing physical characteristics has facilitated their use for the palliative treatment of not only esophageal but gastroduodenal and colonic obstruction as well. The hallmark of these devices is the thin diameter of the compressed stents which allows introducing them into the obstructed segment without the need of aggressive dilatation. Once in place their compression is released and they self expand to a final diameter of approximately 20 mm. Perforation thus occurs rarely and these stents may successfully be placed in over 90% of patients with complete relief of obstruction in over 80%. The most frequent complications are stent dislocation and stent obstruction due to food impaction or tumour overgrowth.

Helicobacter pylori and gastric erosions. Results of a prevalence study in asymptomatic volunteers.

BACKGROUND/AIMS: Helicobacter pylori is considered to be the primary cause of most forms of gastritis, but its role as a causative agent in gastric erosions is unclear. The aim of this study was to estimate the prevalence of gastric erosions and H. pylori infection in asymptomatic volunteers. METHODS: 175 asymptomatic subjects underwent upper gastrointestinal endoscopy. Antral biopsies were taken for bacterial cultures, histology and quick urease (CLO) test. A (13)C-urea breath test was performed after endoscopy. NSAID intake, alcohol consumption and smoking habits were also recorded in each subject. RESULTS: 33 (19%) of 175 asymptomatic volunteers had macroscopic lesions on upper gastrointestinal endoscopy, 7 were H. pylori positive, 26 were H. pylori negative. Gastric erosions occurred in 8% (14 subjects) of all volunteers. 10 subjects were H. pylori negative and 4 H. pylori positive. In 11 volunteers, gastric erosions were restricted to the prepyloric antrum. Only 1 of 14 subjects had a history of NSAID intake and 6 subjects were alcohol abstainers. CONCLUSION: We conclude that gastric erosions occur in a considerable amount of asymptomatic volunteers. They are predominantly localized in the prepyloric antrum and are most likely not associated with H. pylori infection, NSAID intake, smoking or alcohol consumption.

[CA19-9 has no value as a tumor marker in obstructive jaundice]. / CA19-9 hat bei Verschlussikterus als Tumormarker keine Bedeutung.

In the differential diagnosis of pancreatic cancer, CA19-9 appears to be the most sensitive and specific marker currently in use. In the absence of jaundice and at levels greater than 1000 U/ml, the specificity is almost 100%. Levels higher than 1000 U/ml are very uncommon for benign diseases. We report a case of obstructive jaundice due to an impacted stone in the common bile duct with cholangitis, where a CA19-9 level of 61,800 U/ml prompted suspicion of a malignant cause. After treatment the CA19-9 returned to a normal level. One year postoperatively neither abdominal ultrasound nor CT-scan showed any sign of intraabdominal malignancy. Reviewing the literature, we conclude that even very high levels of CA19-9 in cases with obstructive jaundice can be caused by benign diseases. Unlike other tumour markers (alpha-foetoprotein, carcinoembryonic antigen), where exceedingly high levels are definitely caused by malignancy, high levels of CA19-9 can be caused by benign obstructive jaundice. In such cases CA19-9 is useless as a tumour marker. The biliary obstruction must be treated successfully and more diagnostic procedures or even laparotomy performed, to exclude malignancy or treat a benign disease.

Effects of a partially hydrolyzed guar gum on intestinal absorption of carbohydrate, protein and fat: a double-blind controlled study in volunteers.

UNLABELLED: Some dietary fibres have been shown to affect the rate of absorption of dietary carbohydrate, protein and fat as well as exocrine pancreatic function. The aim of the study was to examine the effect of partially hydrolysed guar gum (BENEFIBER), on normal absorption of glucose, amino acid (arginine) and fat. In addition hepatic, pancreatic, renal and haematological side effects were evaluated. METHODS: A double blind, randomized and cross-over design was used. Each subject served as its own control. Ten healthy male volunteers participated in the study. Each subject was randomly assigned to two different dietary regimes for a period of 7 days each. The study was repeated with the other diet for another 7-day period after an interval of at least 1 week. In one study period the subjects took liquid formula diet without fibre and during the other study period they took the same diet with fibre. RESULTS: The results of the study demonstrated that BENEFIBER did apparently not interfere with the normal absorption of glucose, amino acid and fat. In keeping with these observations, insulin release and exocrine pancreatic function were not affected. Haematological, renal and hepatic toxicity were not observed in association with BENEFIBER consumption. CONCLUSION: We conclude that BENEFIBER is a safe source of soluble fibre.

[Therapy concepts in chronic hepatitis C]. / Therapiekonzepte bei chronischer Hepatitis C.

Patients with persistently normal transaminases and without inflammatory changes or fibrosis in liver biopsy have a low risk for progression, respond poorly to antiviral therapy and should thus not be treated for the present. Patients with significant histologic activity or advanced stage of fibrosis are at risk for progression towards cirrhosis. The risk is significantly increased with chronic alcohol consumption even in moderate doses. Treatment with interferon alone results in sustained virological remission in less than 20% of these patients. Treatment success, however, is 2 to 6 times higher under combined treatment with interferon plus ribavirin. The response rate may be further increased with high-dose and daily interferon administration (inductive dosing). The best treatment option for patients with chronic hepatitis C, therefore, is their inclusion in one of the study protocols (examining combinations and induction) currently active in Switzerland.

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.

[Complications in the endoscopic polypectomy of colonic adenomas]. / Komplikationen bei der endoskopischen Polypektomie von Dickdarmadenomen.

Endoscopic polypectomy is associated with a small but definite risk of bleeding and perforation. Patients with large adenomas are thus usually hospitalized for endoscopic resection. In order to evaluate whether these procedures can be performed in the setting of one day surgery, we retrospectively analyzed the complications and results of polypectomy done in the period from 1.1.1990 through 31.12.1994. Of 1399 colorectal adenomas respected in 680 patients, 385 (28%) were larger than 1 cm. Altogether we observed only 3 (0.2%) clinically significant complications: bleeding was seen in 2 patients, of whom only one required transfusion of one unit. One patient required surgery because of perforation after removal of a sessile cecal adenoma with uneventful outcome. These results show that endoscopic resection of colorectal adenomas is safe even if the polyps are large.

Influence of age, gender, hormonal status and smoking habits on colonic transit time.

The factors that influence colonic transit time in healthy humans are not yet clearly defined. The aim of this study was therefore to determine (a) if there are differences in colonic transit time between men and women and (b) if age, female hormonal status or smoking habits are associated with alterations in these parameters. Colonic transit time was measured in 164 asymptomatic subjects (80 males, 84 females) by a radio-opaque marker technique with one single plain abdominal X-ray. Colonic transit time was significantly shorter in men than in women (30 +/- 2 vs. 42 +/- 3 h, P < 0.05). Colonic transit time in non-smoking males was significantly shorter compared with smoking males (26 +/- 2 vs. 40 +/- 5 h, P < 0.05). In females only height and menstrual cycle influenced colonic transit times. We conclude that gender and smoking habits should be considered when studying colonic transit time in health and disease.

Gastric emptying of liquid meals measured noninvasively in humans with [13C]acetate breath test.

The aim of the present study was to develop a breath test to measure liquid gastric emptying rates that would be without radiation exposure and applicable to field testing. Four different test meals were investigated: a glucose meal, an amino acid meal, a fat meal, and a mixed meal (Ensure). The test meals were labeled with two markers, [13C]acetate and PEG-4000 (polyethylene glycol 4000). Gastric emptying rates were measured simultaneously by both breath test and the double-indicator technique in eight healthy male subjects. The appearance of 13CO2 in the breath closely reflected gastric emptying of the four test meals as measured by the double-indicator technique. It is concluded that the [13C]acetate breath test is a reliable, noninvasive test to measure gastric emptying rates of liquid test meals.

Gastrospirillum hominis in asymptomatic, healthy individuals.

Gastrospirillum hominis is a spiral-shaped bacterium found in the stomach. It has been implicated as a possible cause of chronic gastritis. We report two cases of G. hominis colonization observed in a series of 175 healthy, asymptomatic volunteers investigated for Helicobacter pylori. None of the volunteers had symptoms or a history of gastrointestinal disease. Both carriers of G. hominis had histological signs of chronic, active antral gastritis. Multiple tests for H. pylori were negative. The prevalence of this spiral bacterium in healthy, asymptomatic individuals may be as low as in symptomatic persons.

Assessment of lidocaine metabolite formation in comparison with other quantitative liver function tests.

In clinical practice, the seriousness of liver disease is assessed based on the combined information from clinical examination, routine biochemical tests, and liver histology. Recently, the assessment of hepatic lidocaine metabolism has been proposed as a quantitative liver function test offering valuable additional information. To evaluate whether this new liver function test reflects the combined clinical assessment, we prospectively measured lidocaine metabolism in 111 patients with well characterized liver disease. In addition, lidocaine test results were compared with the aminopyrine breath test and the galactose elimination capacity. Lidocaine (1 mg/kg) was injected i.v. and serum concentrations of its main metabolite monoethylglycinexylidide were determined after 15 min. The results varied widely and the means (+/- S.D.) were similar among patients with mild liver disease (46 +/- 23 ng/ml), but significantly (P < 0.05) lower among patients with Child class A cirrhosis (19 +/- 11 ng/ml) or Child class B or C cirrhosis (21 +/- 19 ng/ml). The [13C]aminopyrine breath test, however, gave a better discrimination among patients with increasing severity of liver disease than lidocaine metabolite formation. The galactose elimination capacity finally best separated patients with mild liver disease from those with cirrhosis. The correlations between any two of the different quantitative liver function tests were weak (R2 consistently < 0.2). We conclude that lidocaine metabolite formation, like other quantitative liver function tests that are based on the microsomal metabolism of model compounds, quantitates a very particular enzymatic reaction which may not be representative for the functional reserve of the entire organ.

[Endoscopically inserted plastic endoprosthesis in the palliative treatment of malignant obstructive jaundice]. / Endoskopisch eingelegte Plastikendoprothesen in der palliativen Behandlung des malignen Verschlussikterus.

Experience is reported of palliative treatment for malignant obstructive jaundice by plastic drain positioned in the biliary tract during endoscopic retrograde cholangiopancreatography (ERCP). In the period January 1989 to December 1991, 35 plastic drains (10-12 French) were implanted in 22 patients of mean age 70 (range 51-88) years because of obstruction due to biliary tract carcinoma (n = 10), metastases (n = 5), pancreatic carcinoma (n = 4) and papillary carcinoma (n = 3). Endoscopic positioning was successful in 86% of cases. The early complication rate was 4.5% (cholangitis) and the 30-day mortality 14%. In 89% of cases drainage was effective and the obstructive jaundice subsided within 3 months. Late complications occurred in 36% of patients, involving cholangitis due to drain obstruction (n = 5) and drain displacement (n = 2). In 27% of patients the drain had to be changed 1-3 times, on the first occasion after an average of 146 (range 14-421) days. The patients' median survival was 5 months.

Influence of Helicobacter pylori, sex, and age on serum gastrin and pepsinogen concentrations in subjects without symptoms and patients with duodenal ulcers.

The relation between Helicobacter pylori (H pylori) infection and fasting gastrin and pepsinogen-I and -II concentrations was evaluated in 278 volunteers without symptoms and the results were compared with the values obtained in 35 patients with duodenal ulcers. H pylori infection was determined with the 13C-urea breath test in subjects without symptoms and with endoscopy, biopsy (histology and culture), and quick urease test (CLO-test) in patients with duodenal ulcers. Gastrin and pepsinogen-I and -II concentrations were assayed with specific radioimmunoassay systems. The results clearly indicate that fasting gastrin and pepsinogen-I and -II concentrations were significantly higher in H pylori positive compared with H pylori negative subjects. Neither age nor sex affected basal gastrin and pepsinogen concentrations in H pylori negative subjects. Fasting gastrin, pepsinogen-I and -II concentrations in serum samples were similar in H pylori positive persons with no symptoms and those with duodenal ulcers suggesting that similar mechanisms are involved in increasing plasma concentrations of these variables in both populations. Hypergastrinaemia and hyperpepsinogenaemia are therefore probably secondary to active H pylori infection.

Non-invasive assessment of gastrointestinal motility disorders in diabetic patients with and without cardiovascular signs of autonomic neuropathy.

Twenty six patients with insulin dependent diabetes mellitus underwent a gastric emptying test, a gall bladder contraction test, an orocaecal transit study, and a colon transit test. Eleven patients had signs of cardiovascular autonomic neuropathy, 15 patients were without signs of cardiovascular autonomic neuropathy. Mean gastric clearance of radioopaque markers ingested with a meal averaged 29.5 (2.3) markers per six hours in subjects without cardiovascular autonomic neuropathy compared with 17.8 (2.3) markers per six hours in patients with cardiovascular autonomic neuropathy (p < 0.02). Gall bladder emptying in response to graded CCK8 stimulation was impaired in five of 11 patients with cardiovascular autonomic neuropathy, whereas it was normal in the patients without cardiovascular autonomic neuropathy (p < 0.01). Oral caecal transit times were not significantly different in the two patient groups, whereas colonic transit was slower in the patients with cardiovascular autonomic neuropathy compared with the group without cardiovascular autonomic neuropathy (p < 0.02). There was no correlation between disturbed gastric clearance, impaired gall bladder contraction, and prolonged colonic transit time in the patients with cardiovascular autonomic neuropathy nor was there a correlation between any disturbed motor function and age or duration of diabetes. It is concluded that autonomic neuropathy can affect motor functions throughout the gastro-intestinal tract. Any disturbed motor function in the gut could therefore be one of the numerous expressions of diabetic neuropathy affecting the cardiovascular, the endocrine or the gastrointestinal system.

[Age- and sex-specific standard values of colonic transit time in healthy subjects]. / Alters- und geschlechtsspezifische Normwerte der Dickdarmtransitzeit bei Gesunden.

Use of radiopaque markers with a plain X-ray of the abdomen is a simple technique to measure mean segmental and total colonic transit time. We evaluated 128 healthy volunteers with a mean age of 40 years (range 20-81 years) from three different parts of Switzerland to assess age and sex specific normal transit times. In men and women colonic transit time was not influenced by age. The mean transit time was significantly shorter in men than in women (30 +/- 2 hours versus 41 +/- 3 hours: p less than 0.05). In men the transit time was also influenced by smoking. Non-smoking men had a significantly shorter transit time than smokers (26 +/- 2 hours versus 40 +/- 5 hours: p less than 0.05). In women, neither smoking nor the menstrual cycle influenced transit time. For normal colonic transit time we recommend up to 66 hours for smoking men, up to 44 hours for non-smoking men and up to 70 hours in general for women.

[Is flexible sigmoidoscopy as preventive measure for colorectal carcinoma in asymptomatic patients over 45 practicable?]. / Ist die flexible Sigmoidoskopie bei über 45jährigen asymptomatischen Patienten als Vorsorgeuntersuchung für kolorektale Karzinome praktikabel?

The efficacy of flexible sigmoidoscopy as a screening method for colorectal cancer is still undetermined, and a reduction in mortality due to this cancer by mass screening has not been demonstrated so far. An important precondition for the practicability of screening sigmoidoscopy is its acceptability by the persons to be screened. Acceptability was tested in 294 volunteers without abdominal symptoms from a general medical outpatients clinic. Mean age of participants was 58 years (45-86), 65% were men and 35% women. Sigmoidoscopy was judged harmless by 221 persons (75.1%), painful by 62 (21.1%), very painful by 11 (3.7%), and unacceptable by none. Every participant would have agreed to repeat the examination. In 36 patients 52 polyps were detected, comprising one carcinoma, 18 adenomas (in 15 patients), 32 hyperplastic polyps and one lipoma. We conclude that sigmoidoscopy was well accepted in this study and should be evaluated further as a mass screening method for colorectal cancer.

[Needlestick injuries in hospital personnel and the risk of hepatitis-B infection]. / Nadelstichverletzungen beim Spitalpersonal und Risiko der Hepatitis-B-Infektion.

The risk of employees of the University Hospital of Basel acquiring virus hepatitis B following needle stick injuries (NSI) was evaluated prospectively. Over four years, 555 NSI were reported, resulting in a mean incidence of 48 NSI/1000 persons working/year. Of the injured, 455 (82%) had previously been vaccinated against hepatitis B, 32 (6%) were HBsAg and/or anti-HBc positive, and only 65 (12%) were at risk for HBV infection. The origin of 365 (66%) of the needles implicated in the NSI was identified, and of these 15 (4%) had been contaminated with HBsAg-positive blood. None of the 555 persons with NSI developed hepatitis. We conclude that the risk of HBV infection following NSI is low at our institution, but general measures need to be enforced to reduce the incidence of NSI in view of the potential risk that other infectious diseases may be transmitted by NSI.