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New strategies have led to better results in the treatment of HCV infection during the last few years. At present the recommended treatment for patients with chronic hepatitis C is a combination of pegylated interferon and ribavirin. The sustained virological response rate of this combination therapy is 42 - 48 % for patients with genotype 1 after a course of 48 weeks and 80 % for patients with genotype 2 or 3 after a course of 24 weeks. New nucleoside analogs may lead to a better tolerance and better outcomes. A new approach is the long term monotherapy with pegylated interferon in order to reduce the progression of fibrosis and the incidence of cirrhotic complications. At present the effectivity of protease inhibitors and of a therapeutic immunisation with the E1 envelope protein of the hepatitis C virus are being examined. Because the optimal treatment strategy for patients with an acute hepatitis C infection is still unclear, these patients should be included in clinical studies.

BACKGROUND AND OBJECTIVE Hepatocellular carcinoma (HCC) ranks eighth among malignant tumors worldwide. Western countries belong to areas of low HCC prevalence, but incidence of HCC is rising. The aim of the present, retrospective study was to determine changes in the incidence rates and risk factors for HCC in Germany based on the data of a single center. PATIENTS AND METHODS Epidemiological data of 205 consecutive patients with HCC (163 males, 42 females, mean age 64+/-1 years), admitted to the University clinic Dusseldorf between January 1988 and December 2001, were evaluated. For comparison this time period was divided into two equal intervals (1988 - 1994 and 1995 - 2001). RESULTS The number of newly diagnosed HCC has more than doubled in the years 1995 - 2001 compared to the years 1988 - 1994. Chronic hepatitis C (HCV), hepatitis B (HBV), and chronic alcohol abuse accounted for almost 80 % of HCC. The number of HCV-associated HCC increased from 31.0 % in the years 1990 - 1995 to 44.6 % (p < 0.04) in the years 1996 - 2001, whereas the proportion of HBV-associated HCC decreased. There were no changes in the Okuda tumor stage, tumor diameter and alpha-fetoprotein levels at the time of HCC diagnosis throughout the years 1988 - 2001. More than 65 % of HCC were non-resectable at the time of HCC diagnosis due to tumor diameter or number of tumor lesions. CONCLUSION Screening for HCC, possibly rising in its incidence, should be further improved, taking into account that chronic HCV infection is the major risk factor for HCC in Germany.

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

Summary. Previous large multicentre trials reported sustained virological response (SVR) rates of 45–80% in chronically infected hepatitis C virus (HCV) patients. However, it is unclear whether such a treatment success is also achieved in daily routine and to what extent it depends on expert hepatological supervision. This was retrospectively analysed in patients presenting at our outpatient department during May 1997 and March 2004 and receiving at least one treatment dose. A total of 302 treatment-naive HCV patients [72% genotypes 1 or 4 (n = 215), 25% genotypes 2/3 (n = 78) and 3% undetermined genotype (n = 9)] were included in the analysis. Out of these, 196 patients consulted an expert hepatologist at least once every 3 months during treatment [regular visitors (RV)], whereas in 106 patients treatment was performed and supervised by a general practitioner (irregular visitors). Both patient groups did not differ in their baseline characteristics. However, the virological response rates at the end of treatment (ETR; 146/196, 74%vs 51/106, 48%, P

Bile leak is a well-known complication of cholecystectomy. Endoscopic drainage and decompression of the biliary system including temporary insertion of a biliary stent is generally considered the treatment of choice. We report the successful obliteration of a bile leak using fibered platinum coils placed under fluoroscopic guidance after stent treatment had failed.

A 38 year old man presented to our clinic with a four year history of histologically confirmed Crohn’s colitis refractory to treatment and oligoarticular pain and swelling, especially of the knees, interpreted as Crohn’s arthritis. …

New strategies have led to better results in the treatment of HCV infection during the last few years. At present the recommended treatment for patients with chronic hepatitis C is a combination of pegylated interferon and ribavirin. The sustained virological response rate of this combination therapy is 42 - 48 % for patients with genotype 1 after a course of 48 weeks and 80 % for patients with genotype 2 or 3 after a course of 24 weeks. New nucleoside analogs may lead to a better tolerance and better outcomes. A new approach is the long term monotherapy with pegylated interferon in order to reduce the progression of fibrosis and the incidence of cirrhotic complications. At present the effectivity of protease inhibitors and of a therapeutic immunisation with the E1 envelope protein of the hepatitis C virus are being examined. Because the optimal treatment strategy for patients with an acute hepatitis C infection is still unclear, these patients should be included in clinical studies.

Hepatocellular carcinoma (HCC) ranks eighth among malignant tumors worldwide. Western countries belong to areas of low HCC prevalence, but incidence of HCC is rising. The aim of the present, retrospective study was to determine changes in the incidence rates and risk factors for HCC in Germany based on the data of a single center.Epidemiological data of 205 consecutive patients with HCC (163 males, 42 females, mean age 64+/-1 years), admitted to the University clinic Düsseldorf between January 1988 and December 2001, were evaluated. For comparison this time period was divided into two equal intervals (1988 - 1994 and 1995 - 2001).The number of newly diagnosed HCC has more than doubled in the years 1995 - 2001 compared to the years 1988 - 1994. Chronic hepatitis C (HCV), hepatitis B (HBV), and chronic alcohol abuse accounted for almost 80 % of HCC. The number of HCV-associated HCC increased from 31.0 % in the years 1990 - 1995 to 44.6 % (p0.04) in the years 1996 - 2001, whereas the proportion of HBV-associated HCC decreased. There were no changes in the Okuda tumor stage, tumor diameter and alpha-fetoprotein levels at the time of HCC diagnosis throughout the years 1988 - 2001. More than 65 % of HCC were non-resectable at the time of HCC diagnosis due to tumor diameter or number of tumor lesions.Screening for HCC, possibly rising in its incidence, should be further improved, taking into account that chronic HCV infection is the major risk factor for HCC in Germany.

Hepatitis C is one of the world's leading infectious diseases. The interferon-ribavirin combination therapy is the new standard for the treatment of hepatitis C in naive and relapse patients. Virological sustained response rates can be more than doubled by the IFN-ribavirin combination therapy compared to IFN-monotherapy and treatment duration can be reduced to six months in many cases. The IFN-ribavirin combination therapy has a high relative benefit in patients with unfavorable predictive parameters like high viral load, HCV genotype-1 infection and compensated liver cirrhosis. Anemia is the most important side effect of the guanosin analogue ribavirin. There are no official therapeutic recommendations for non-responder patients at present. These patients should be treated within controlled clinical trials. Monotherapy with PEG(pegylated)-interferons and combination therapies with PEG-interferons and ribavirin are the most promising future therapeutic options.

Nucleoside analogues are promising agents for the treatment of chronic hepatitis B infection (HBV-DNA-positive by hybridization assay). The drug being studied most intensively is Lamivudine (Zeffix) which has recently been approved in Germany. When given orally once daily (100 mg) Lamivudine is well-tolerated and suppresses HBV-DNA to undetectable levels in the majority of patients. Since relapse is frequent when medication is stopped long-term treatment (at least until seroconversion of HBeAg) is warranted. Indications for lamivudine monotherapy are patients with chronic hepatitis B in which interferon (IFN) is contraindicated or patients who did not respond to a previous course of interferon. Further indications are the HBV-DNA-positive cirrhosis prior to liver transplantation (OLT) and the HBV-reinfection after OLT. The main problem of long-term monotherapy with lamivudine is viral resistance. The clinical impact of the resistant mutants is often not clear. Withdrawal or even continuation of the medication may be acceptable approaches. Other nucleoside analogues like Entecavir or Adefovir are currently being tested in clinical studies. Famciclovir was investigated preferably in patients with decompensated liver disease or HBV-reinfection after OLT. Because of conflicting results the drug should only be used under study conditions. In IFN-naive patients with chronic hepatitis B (and compensated liver disease) alpha-interferon is still the first-line therapy. With a standard course of interferon 30-40% of the patients become seronegative for HBeAg as compared with 16-17% when treated with lamivudine for twelve months. Combination of lamivudine and interferon is not more effective than IFN alone. In the future combined antiviral treatment is likely to replace monotherapy.

The monoclonal antibody C7-50 binds to the HCV core protein with high sensitivity and specificity. The coding sequences of the variable domains of the antibody were determined following cDNA cloning of the Fab and sFv fragments. Subsequently, intracellular expression and binding of these antibody fragments to the HCV core protein as a potential antiviral approach were studied. There was high specificity and sensitivity of binding of bacterially expressed, recombinant C7-50 Fab to HCV core as measured by EIA and immunoblot. For expression in mammalian cells, the C7-50 antibody was subcloned in the sFv format by the introduction of a (Gly(4)Ser)(3) linker spaced between light and heavy chains. Northern and Western blot analysis as well as confocal microscopy established the targeted expression of the C7-50 sFv antibody fragment in the endoplasmic reticulum of transfected cells. The colocalization and intracellular binding of the antibody fragment to HCV core protein was confirmed by immunoprecipitation and subsequent immunoblot analysis. This study demonstrates that gene delivery of cDNA coding sequences inducing intracellular expression of C7-50 antibody fragments leads to binding of the antibody fragment to the HCV core protein within the secretory compartment of transfected cells. Intracellular immunization represents a promising antiviral approach to interfere with the life cycle of HCV.

Viral serum concentrations are considered to have a clinical, prognostic and epidemiological impact on patients with hepatitis C infection. The purpose of this study was to test whether quantitation of HCV-RNA is possible by PCR in combination with DNA-ELISA.PCR with 25 to 35 cycles was performed with variable concentrations of cloned HCV-cDNA or the serum of patients with chronic hepatitis C. The amplified PCR-products were detected by agarose gel or by DNA-ELISA.The detection limit of PCR with DNA-ELISA or gel detection decreased with increasing numbers of PCR cycles. However, the correlation of the optical density of the DNA-ELISA with the HCV-cDNA concentration decreased with increasing numbers of PCR as well (r=0.8 vs. r=0.29; 25 vs. 35 PCR-cycles). HCV-RNA was found in the sera of 19 of 30 patients (63%) with chronic hepatitis C by gel detection and in 14 of 30 patients (47%) by DNA-ELISA subsequent to PCR with 35 cycles.The PCR/DNA-ELISA technique allows a semiquantitative determination of HCV-cDNA concentrations down to 103 genomes/ul. However, to obtain a reasonable sensitivity for HCV concentrations in the serum of patients with hepatitis C, the number of PCR cycles has to be increased to numbers too high to provide reliable quantification. Further studies should be done to evaluate whether the detection systems can be improved to obtain a sufficient sensitivity for quantitative HCV-PCR. A prerequisite for the use of PCR in combination with quantifiable detection systems is that a PCR-cycle number is chosen that keeps amplification within the logarithmic phase.

The prognosis of chronic hepatitis C virus (HCV) infection is still ill-defined. The present study prospectively evaluated mortality and complications in a large cohort of patients with chronic hepatitis C. The study included 838 anti-HCV and HCV-RNA-positive patients who were followed for 50.2 +/- 26.9 months (mean +/- SD; range, 6-122 months) in a prospective protocol. During follow-up, 62 patients died (31 from liver disease and 31 from other causes), and 12 patients needed liver transplantation. When compared with a matched general population, hepatitis C increased mortality mainly when cirrhosis was present and in patients who were less than 50 years old at study entry. During follow-up, a further 30 patients developed nonlethal complications of cirrhosis. By multivariate regression, survival was decreased by cirrhosis, long disease duration, history of intravenous drug abuse, and excessive alcohol consumption, whereas interferon therapy improved survival. Alanine transaminase (ALT), bilirubin, sex, and genotype had no effect on survival. The risk of hepatocellular carcinoma (HCC) (n = 17) was increased by cirrhosis and to a lesser degree by long disease duration and high bilirubin, whereas interferon therapy, genotype, and other factors had no effect. Chronic hepatitis C is a disease with considerable mortality and morbidity when cirrhosis is present at diagnosis. Patients who acquire the infection early in life have a markedly increased mortality even when cirrhosis is absent at diagnosis. The age at diagnosis therefore should play a major role in therapeutic considerations. The present data also suggest that interferon therapy has a long-term clinical benefit, although it did not reduce the risk of liver cancer.

The present study prospectively evaluated the value of liver biopsy in patients with chronic hepatitis B (N=75) and C (N=135) prior to interferon therapy. Biopsy specimens revealed cirrhosis in 26% of patients with hepatitis B and 30% with hepatitis C. Although cirrhosis was not predictable by laboratory values in individual patients mean gamma-GT, alkaline phosphatase, and bilirubin levels were significantly higher in patients with cirrhosis compared to those without. Since cirrhosis significantly impairs the response rate to interferon therapy in hepatitis C but not in hepatitis B, liver biopsy is important for the management of chronic hepatitis C infection. In 88% of patients with serum HBV-DNA, irrespective of the serum HBeAg status, chronic active hepatitis was seen. Similarly, chronic active hepatitis was found in 84% of patients with elevated aminotransferases and hepatitis C antibodies. Thus, chronic active hepatitis was diagnosed in the majority of cases with chronic viral hepatitis, showing that this histopathological diagnosis is of little additional value for the recommendation on interferon treatment in these patients. However, none of the other grading systems of liver biopsy specimens described so far have been evaluated for their ability to predict overall prognosis or response rates to interferon therapy. Therefore, the physician is presently left with the questionable value of a procedure with well-known risks and costs in patients suitable for interferon treatment. Hence, prospective randomized controlled studies to evaluate histopathological grading systems are urgently needed to redefine the necessity of liver biopsy in this routine clinical setting.

Polyunsaturated phospatidyl-choline (PPC) has been shown to reduce serum aminotransferases in experimental hepatitis. This multi-center, randomized, double-blind, placebo-controlled trial evaluated the effects of PPC in patients with chronic hepatitis B and C in combination with interferon alpha 2a or 2b. The diagnosis of chronic viral hepatitis was based on an abnormal serum alanine aminotransferase (ALT) value (more than twice the upper value of normal), viral replication and chronic hepatitis found on liver biopsy.Patients received 5 million I.U. (Hepatitis B) and 3 million I.U. (hepatitis C) interferon s.c. thrice weekly for 24 weeks, respectively, and were randomly assigned to additional oral medication with either 6 capsules of PPC (total daily dose: 1.8 g) or 6 capsules of placebo per day for 24 weeks. Biochemical response to therapy was defined as a reduction of ALT by more than 50% of pre-treatment values. The responders were treated for further 24 weeks after cessation of interferon therapy with either PPC or placebo.176 patients completed the study protocol (per-protocol population: 92 in the PPC and 84 in the placebo group). A biochemical response (50% ALT reduction) was seen in 71% of patients who were treated with PPC, but only in 56% of patients who received placebo (p0.05). PPC increased the response rate in particular in patients with hepatitis C: 71% of those patients responded in the PPC group versus 51% in the placebo group (p0.05). Prolonged PPC therapy given to responders beyond the cessation of interferon therapy tended to increase the rate of sustained responders at week 48 in patients with hepatitis C (41% versus 15% in the control group; p = 0.064). In contrast, PPC did not alter the biochemical response to interferon in patients with hepatitis B. PPC did not accelerate elimination of HBV-DNA, HBeAg and HCV-RNA.In conclusion, PPC may be recommended in patients with chronic hepatitis C in combination with interferon and after termination of interferon in order to reduce the high relapse rate. PPC may not be recommended for patients with chronic hepatitis B. In contrast to IFN and other antiviral agents PPC does not carry major risks and is tolerated very well.

Chronic hepatitis C and B are the main causes of hepatocellular carcinoma (HCC) worldwide. Little is known about the etiology of HCC in Germany which is regarded as a low-prevalence area for viral hepatitis C (HCV) and B (HBV). To assess the etiologic factors of HCC in Germany we have retrospectively analyzed the records of 100 consecutive patients with hepatocellular carcinoma in our clinic. HCC-patients with documented status on HCV/HBV-infection and daily alcohol intake (n = 55) had HCV antibodies in 53%, HBs-Ag in 20%, isolated chronic alcohol abuse in 11% and genetic hemochromatosis in 2%. In 13% of the HCC-patients no risk factor could be identified. Coinfections with HCV and HBV were not observed. Liver cirrhosis was present in 90% of the HCC-patients. In histologically confirmed HCC (n = 71) serum alpha-fetoprotein level was normal (8.5 ng/ml) in 20%, moderately elevated (8.5-300 ng/ml) in 48% and considerably elevated (300 ng/ml) in 32% of the patients. Only 31% of all patients presented with small single lesions (or = 5 cm) without evidence for extrahepatic metastases or portal vein thrombosis. Only 30% of the HCC-patients could be treated with a curative intention (28 hepatic resections, one orthotopic liver transplantation). Patients who underwent resection had cumulative 6-month, 1-year, 2-year and 3-year survival rates of 83.8%, 65.9%, 54.3% and 24.8% respectively. Median survival time after resection was 24.8 months compared with 5.8 months in symptomatically treated patients with unresectable HCC (n = 39). Patients with hepatitis C-associated HCC were significantly older than patients with hepatitis B-associated HCC (mean values: 63.2 vs. 54.2 years). Frequency of cirrhosis, tumor stage, alpha-fetoprotein level and prognosis did not differ between groups. In conclusion hepatocellular carcinoma was predominantly associated with chronic HCV-infection. Most patients presented with normal or moderately elevated serum AFP-levels. Prognosis was poor even after hepatic resection.

The present analysis evaluates whether the type, dose, and duration of interferon treatment affect its short- and long-term responses, and also analyzes whether the presence of liver cirrhosis predicts response rates.The present review analyzes 52 randomized clinical trials of a-interferon in chronic NANB and C hepatitis. Normalization of serum ALT during and 3-6 months after interferon treatment served to assess short- and long-term response rates.Interferon initially induced ALT normalization in 1499/2927 patients (51.2%); due to a high relapse rate (50%), only 482/2218 patients (21.7%) still had normal ALT values three months after interferon therapy had been stopped. Nevertheless, ALT normalization was increased more than 8-fold by a-interferon treatment (21.7%) when compared with the spontaneous normalization rate in untreated or placebo-treated controls (22/822 controls; 2.7%)(chi 2 = 156.1; por = 10(-15). The long-term response rate significantly increased with increasing weekly doses and with the duration of interferon therapy (r = 0.25 and 0.38 with p0.01, respectively). Correspondingly, the response rate was correlated most closely with the total dose of interferon given (r = 0.49, p0.001). Total interferon doses240 M.U. resulted in a threefold higher long-term response when compared with doses240 M.U. (X2 = 103.3; por = 10(-15). The presence of cirrhosis markedly reduced the response rate to almost 1/3 of noncirrhotic patients (chi 2 = 12.1; p = 0.00013). The response rate did not depend on the type of interferon used.The present data strongly suggest that future studies which evaluate effects of a-interferon in chronic hepatitis C should focus on higher doses and longer duration of therapy, preferably in noncirrhotic patients.

Recent advances in our understanding of viral hepatitis involve the discovery and further characterization of the hepatitis C virus and the interferon treatment of patients with chronic viral hepatitis. Liver cirrhosis and primary hepatocellular carcinoma can develop after some years of disease. Interferon is the only effective treatment, which may improve symptoms and prognosis in some patients. Long-term responses with termination of viral replication are seen in 40% of patients with hepatitis B and 15-25% of patients with hepatitis C. In some patients complete elimination of the virus occurs. Higher response rates are achievable in subgroups of patients with favourable prognostic constellations. Patients have to be informed about side-effects and risks of interferon therapy. Treatment in uncomplicated cases is performed on an outpatient basis. The present paper reviews diagnosis, indications, contraindications and practical considerations concerning interferon treatment in patients with chronic viral hepatitis.

The incidence of hepatitis C infection is increased in subjects with human immunodeficiency virus infection, although the relative frequency of hepatitis b infection is higher than that hepatitis c. The present study assessed the effect of IFN-a on chronic hepatitis C in HIV infected patients.Twenty patients with chronic hepatitis C, nine positive for antibodies to the human immunodeficiency virus and eleven HIV-seronegative, were treated with interferon a-2b.Five HIV-positive patients responded to therapy with a complete (three) or partial (two) remission of hepatitis at the end of treatment. A sustained response was achieved in four patients. From the HIV-negative patients eight responded with a complete (six) or partial (two) remission. The response was sustained in six patients. Hepatitis C virus-RNA became at least temporarily undetectable in three HIV-positive and six HIV-negative patients. No severe toxicity of interferon treatment was seen in either the HIV-positive or the HIV-negative patients.The present results indicate that interferon treatment of chronic hepatitis C in HIV-positive patients is successful in a considerable number of individuals. However it might be inferior to the results in HIV-negative patients.

Thorough differential diagnosis in patients with autoimmune hepatitis is important since other liver disorders need different treatment regimen. Elevated transaminases and gamma-globulines and autoantibodies should make one think of autoimmune hepatitis. Liver biopsy is helpful but usually not a definitive proof of the diagnosis. Immunosuppressive therapy has to be administered for years and possibly leads to serious side effects. Therapy should only be discontinued if a complete remission is induced. Relapses after cessation of medical treatment occur frequently. If no remission is achieved lifelong immunosuppressive therapy has to be given. In decompensated disease liver transplantation offers a treatment with good prognosis.

Since 3 years there is an effective enzyme replacement therapy for patients with Gaucher's disease which is the most prevalent sphingolipid storage disease. Also the diagnostic procedures have recently been improved. This study reports about the results of longterm enzyme replacement therapy and the diagnostic workup in 18 patients with Gaucher's disease.Since June 1991, 18 patients with moderate to severe degree of Gaucher's disease were treated by administration of modified human glucocerebrosidase on regular bases in the University Hospital Düsseldorf. According to the severity of the disease, glucocerebrosidase infusion was performed every 2 weeks. The dosage was individually chosen according to the severity of the disease.Within 3 to 4 months all patients showed an improvement of laboratory findings, of hepatosplenomegaly and of their general well-being.The advances in our understanding of this disease need to be publicized because an early diagnosis and timely enzyme replacement guarantees almost all patients with the adult type of Gaucher's disease to live a normal life without complaints and complications.

In some patients differentiation between autoimmune hepatitis and chronic viral disease may be difficult. In patients with chronic active hepatitis the coincidence of various types of autoantibodies and antibodies to hepatitis C virus (HCV-Ab) has been reported. It is important to diagnose the true etiology of the underlying liver disease because treatment for viral disease and autoimmune hepatitis is different. This paper reports about five patients who were referred to the liver outpatient clinic with the diagnosis of chronic active hepatitis. All of them had antibodies to liver-pancreas-antigen (LP-Ab) and HCV-Ab. Some authors believe that LP-Ab and anti-soluble-liver-antigen antibodies (SLA-Ab) are found with the same entity of autoimmune hepatitis. Nevertheless none of our patients had detectable antibodies against Cytokeratin 8/18, the major target antigen of SLA-Ab positive autoimmune hepatitis. Serum transaminases were elevated for more than 6 months and all patients were positive for HCV-RNA by PCR. Three patients had a history of exposure to blood products. In all five patients liver biopsy showed chronic active hepatitis compatible with chronic hepatitis C. All patients were treated with alfa-interferon. In four of five patients interferon led to improvement or normalization of serum transaminases. Thus we conclude that in a considerable number of patients with chronic active hepatitis associated with both LP-Ab and HCV-Ab, hepatitis C virus is the true etiology. Such patients with both LP-Ab and HCV-Ab may successfully be treated with alfa-interferon.(ABSTRACT TRUNCATED AT 250 WORDS)

Diese Ubersicht analysiert den aktuellen Wissensstand uber die Regulation der exokrinen Pankreasfunktion. Die unterschiedlichen stimulierenden und hemmenden Regulationsmechanismen spielen sich dabei auf verschiedenen Ebenen ab (s. folgende Ubersicht).

The development of potent and specific CCK-receptor antagonists made it possible to evaluate the physiological role of CCK for various gastrointestinal functions. The results of these studies show that CCK is the hormone which principally mediates meal-induced gallbladder emptying. In addition, CCK appears to play an important role in maintaining the fasting muscular tone of the gallbladder. In contrast, CCK-antagonists could inhibit only about 50% of the meal-stimulated pancreatic exocrine secretion. Because of their marked relaxing effect on the gallbladder, CCK-antagonists might become an important clinical tool for treatment of gallbladder spasms and colics. On the other hand, long-term application of CCK-antagonists will increase the risk of stone formation in the gallbladder. CCK-antagonists also had beneficial effects in some animal models of acute pancreatitis. As yet, it is unclear whether CCK-antagonists might become useful for the treatment of human pancreatitis. Since CCK-antagonists only slightly inhibited pancreatic growth, it is unlikely that they will exert major inhibitory effects against growth of pancreatic carcinoma. CCK-antagonists failed to alter gastric emptying of a normal mixed solid-liquid meal, but accelerated gastric emptying of purely liquid meals. Thus, CCK-antagonists are not likely to become useful agents to treat alterations of gastric emptying. The studies with CCK-antagonists further showed that CCK plays only a minor role in the regulation of the motility of the small and large intestine. CCK is probably not involved in the regulation of the gastrocolonic response after a meal. Some reports indicate that CCK-antagonists might increase colonic transit and might therefore be useful to treat constipation.