Search

Copyright of Der Gastroenterologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in some areas of the world. The prognosis of HCC patients is generally very poor with a 5-year survival rate of less than 5%. Therapeutic strategies include surgery (resection or liver transplantation) and non-surgical interventions, such as percutaneous ethanol injection or radiofrequency thermal ablation as well as transarterial embolization or chemoembolization. Therefore, the development and evaluation of novel HCC treatment strategies such as the use of antiangiogenic, antiproliferative or antiinflammatoric drugs, immune therapeuticals, gene therapy and internal or external radiation are of utmost importance. This review should give an overview of possible alternative therapies in HCC treatment.

Therapeutic options for patients with hepatocellular carcinoma (HCC) are still limited. Only patients with small HCC are considered for curative treatment options such as resection, liver transplantation or local ablation. Systemic treatment of advanced HCC is still impaired by the high level of resistance to chemotherapy and irradiation. In addition, most patients with HCC are highly susceptible to toxic side effects due to their impaired liver function. Novel treatment options are based on the increasing understanding of molecular mechanisms involved in tumorigenesis, tumor progression and metastasis. Such "targeted therapies" aim at growth factors and their receptors, intracellular signal transduction and cell cycle control. Anti-angiogenesis targets the tumor vasculature. Gene therapeutic strategies are based on the transfer of therapeutic genes in target tissues to express highly active proteins such as suicide genes or cytokines. Tumor cell death by cell lysis is the mechanism of oncolytic viruses, which are able to selectively replicate in tumor cells. This mechanism may be augmented by the addition of therapeutic genes expressed by recombinant oncolytic viruses. The induction of a potent immune response to tumor antigens by vaccination strategies or by adoptive transfer of activated immune cells aim at the specific destruction of tumor cells by effector T-cells targeted to tumor antigens.

History: A 64-year old somnolent man was admitted to the emergency department with a reported seizure half an hour earlier. Due to similar episodes the patient had been treated with antiepileptics in the past. The patient s past history revealed a partial gastrectomy (Billroth II) more than ten years ago., Diagnostic Findings and Therapy: At the time of admission blood glucose was 31 mg/dl. Other routine laboratory analyses and the clinical examination were normal. In addition, a detailed neurological examination and a cranial CT-scan were normal. Due to the hypoglycemia a dumping syndrome was suspected. A three hour oral glucose tolerance test (OGTT) resulted in a late hypoglycemia, establishing the diagnosis of late dumping. After adaptation of the patient's diet no further hypoglycemic episodes occurred., Conclusion: Manifestation of a dumping syndrome may occur even years after gastrectomy. Therefore, in patients presenting with hypoglycemia and a history of gut surgery, a dumping syndrome should be suspected. Furthermore, seizures due to hypoglycemia may be the only manifestation of late dumping.

Malignant lesions of the liver are among the most frequent and difficult problems in clinical practice. Liver tumors can be classified as primary (hepatocellular carcinoma HCC, cholangiocarcinoma CC) and secondary liver lesions (metastasis). The therapeutic principle of resecting liver tumours, applies to both types of liver lesions. Unfortunately many patients with primary and secondary liver lesions are inoperable because of technical difficulties or comorbidity. This stimulated the development of percutaneous ablation methods. These procedures allow to destroy tumors percutaneously with alcohol, acetic acid, radiofrequency, microwaves or laser. Potential applications and limitations of the methods are discussed.

Gene therapy is based on the transfer and the expression of therapeutic genes in specific target cells. For the treatment of genetic diseases gene therapeutic approaches aim at replacement of the deficient gene or at the correction of the genetic defect. Malignant diseases and an increasing number of other acquired diseases are additional targets for gene therapeutic strategies. For gene therapy to become a potential future treatment option, safe and therapeutically efficient gene transfer into specific target cells is a central requirement. A variety of nonviral and viral vector systems have been developed. Nonviral vectors transfer genes are far less efficient than viral vectors, but they have advantages due to their low immunogenicity and their large size capacity for therapeutic DNA. To improve the function of nonviral vectors, the addition of viral functions such as receptor mediated uptake, enhanced endosomal release and nuclear translocation of DNA may finally lead to the development of an artificial virus. In contrast, natural viruses are already highly developed structures for the transfer of nucleic acids. Recombinant viruses can be used for efficient gene transfer. Retroviruses, adeno-associated viruses and lentiviruses are suitable for gene therapeutic approaches which are based on the permanent expression of therapeutic genes such as the correction of enzyme deficiencies or the manipulation of hematopoetic stem cells, as they are able to integrate nucleic acids into the cellular genome. In contrast, adenoviral vectors result in highly efficient, but transient gene expression and are therefore especially useful for the treatment of malignant tumors. Novel developments of viral vectors mainly aim at the reduction of immunogenicity, increase of capacity for therapeutic genes and at improved vector production. Viruses which replicate selectively in tumor cells leading to tumor cell lysis represent a novel generation of viral vectors, which can further be improved by the addition of therapeutic genes resulting in enhanced tumor toxicity.

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.

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.