Das hepatozelluläre Karzinom

Hepatocellular cancer (HCC) is the most common cause of death among patients with liver cirrhosis. Screening programs for high-risk patients allow diagnosis at an early stage, when curative treatment options can be offered. Contrast-enhanced imaging modalities are used for diagnosis, with a typical finding in the respective imaging technique being sufficient to establish the diagnosis for lesions >2 cm. Depending on the imaging results, biopsy for histological confirmation of the diagnosis has to be considered for lesions 1–2 cm in diameter. Lesions <1 cm should be controlled after 3 months. In patients without chronic liver disease, histological confirmation is always required. According to stage-dependent treatment algorithms, surgical options are the primary treatment for early-stage disease (resection, orthotopic liver transplantation). In the case of contraindications, radiofrequency ablation (RFA) and transarterial chemoembolization (TACE) can also be considered. The latter is the treatment modality of choice for intermediate-stage disease in which curative options are no longer available. Further ablative and radiological interventional therapy modalities are under current evaluation in clinical studies, also in combination with systemic therapies. For advanced-stage disease in patients with good liver function, systemic therapy with sorafenib is indicated. Further targeted therapies are currently not available. Data of a phase-III trial that has been recently published as abstract confirm the efficacy of Regorafenib as second line treatment. Additionally new data from international multicentric genome sequencing projects suggest further promising therapeutic targets. An effect of sorafenib in an adjuvant setting could not be confirmed.     

Management of small hepatocellular carcinoma

In the last years the incidence of hepatocellular carcinoma (HCC) is rising in cirrhotic patients worldwide. Due the importance of early and definite diagnosis of HCC, any nodular lesion detected in patients with chronic liver disease should be considered as suspicious for HCC. The screening and surveillance programs in patients with liver diseases have increased the number of small HCC detected at an early stage, when the therapeutic options available are able to provide benefit. The introduction of new imaging techniques has improved the accuracy of characterizing these nodules. According to the EASL recommendations, contrast-enhanced computed tomography (CT), contrast enhanced ultrasound (US) and magnetic resonance (MR) with different MR-contrast agents are currently used to characterize liver lesions. Imaging guided biopsy is recommended for small nodules or in lesions without typical features (arterial hypervascularization) in at least two imaging techniques. Frequently the differential diagnosis of small nodules is complicated by discordant vascularity and recent studies have also demonstrated the presence of small hypovascular HCC at perfusional US and helical CT. At present, different treatment options can be offered to patients with diagnosis of small HCC at an early stage; percutaneous techniques, surgical resection and liver transplantation can provide benefit in properly selected patients. This review describes some critical points regarding the detection, diagnosis and therapeutic management of small nodules of HCC in cirrhotic patients.     

Nonoperative therapies for combined modality treatment of hepatocellular cancer: expert consensus statement

Although surgical resection and liver transplantation are the only treatment modalities that enable prolonged survival in patients with hepatocellular carcinoma (HCC), the majority of HCC patients presents with advanced disease and do not undergo resective or ablative therapy. Transarterial chemoembolization (TACE) is indicated in intermediate/advanced stage unresectable HCC even in the setting of portal vein involvement (excluding main portal vein). Sorafenib has been shown to improve survival of patients with advanced HCC in two controlled randomized trials. Yttrium 90 is a safe microembolization treatment that can be used as an alternative to TACE in patients with advanced liver only disease or in case of portal vein thrombosis. External beam radiation can be helpful to provide local control in selected unresectable HCC. These different treatment modalities may be combined in the treatment strategy of HCC and also used as a bridge to resection or liver transplantation. Patients should undergo formal multidisciplinary evaluation prior to initiating any such treatment in order to individualize the best available options.     

The Treatment of Cholangiocarcinoma: a Hepatologist’s Perspective

Cholangiocarcinoma (CCA) is a rare but lethal adenocarcinoma with cholangiocyte differentiation that arises within the biliary tree at variable locations. Curative options are available in the form of surgical resection and/or liver transplantation (LT) in early stage CCA; however, these are offered to a small fraction of patients as they are usually asymptomatic and remain undiagnosed. Primary sclerosing cholangitis (PSC) is a well-known risk factor of CCA, and cirrhosis, viral hepatitis, and metabolic syndrome are recently identified as risk factors of CCA. This emerging evidence places hepatologists in a vital position to diagnose, prognosticate, and manage CCA by planning treatment of each individual patient based on the stage and extent of malignancy. With appropriate selection of patients and the involvement of a multidisciplinary team, surgical resection of localized CCA, LT coupled with neoadjuvant chemoradiation for perihilar CCA, or locoregional or systemic chemotherapy and/or endoscopic interventions for advanced CCA can be offered.     

Prognosis prediction and staging

Staging and prognosis assessment are critical steps in the management of patients with hepatocellular carcinoma. This cancer is a complex disease usually associated with chronic liver disease, and any attempt to assess the prognosis should consider tumour burden, degree of liver function impairment and evaluation of cancer-related symptoms. In addition, for any staging system to be meaningful it has to link staging with treatment indication and this should be based on robust scientific data. Currently, the only proposal that serves both aims is the Barcelona Clinic Liver Cancer (BCLC) staging system. It divides patients into very early/early, intermediate, advanced and end-stage. Very early/early stage HCC patients should be considered for potentially curative options such as resection, transplantation and ablation. Patients at intermediate stage benefit from chemoembolization, while patients at an advanced stage or who cannot benefit of options of higher priority have sorafenib as standard of care. Finally, patients at end-stage should receive best supportive care.     

Update on chronic hepatitis C in HIV/HCV-coinfected patients: viral interactions and therapy

With highly active antiretroviral therapy (HAART), HIV-infected patients can now live longer and healthier lives, and other comorbid diseases, such as chronic hepatitis C, have emerged as a significant health concern. Coinfection with the hepatitis C virus (HCV) may limit life expectancy because it can lead to serious liver disease including decompensated liver cirrhosis and hepatocellular carcinoma. HCV-induced fibrosis progresses faster in HIV/HCV-coinfected persons, although HAART may be able to decrease this disease acceleration. Combination therapy for HCV with interferon and ribavirin can achieve a sustained viral response, although at a lower rate than in HCV-monoinfected patients. Combination treatment with pegylated interferon and ribavirin will probably emerge as the next HCV therapy of choice for HIV/HCV-coinfected patients. HCV combination therapy is generally safe, but serious adverse reactions, like lactic acidosis, may occur. Cytopenia may present a problem leading to dose reductions, but the role of growth factors is under study. All HIV/HCV-coinfected patients should be evaluated for therapy against the hepatitis C virus. A sustained viral load will probably lead to regression of liver disease, and even interferon-based treatment without viral clearance may slow down progression of liver disease. HIV/HCV-coinfected patients who have progressed to end-stage liver disease have few therapeutic options other than palliative care, since liver transplants are generally unavailable. The mortality post-transplant may be higher than in HCV-monoinfected patients. We are entering an era where safe and effective HCV therapy is being defined for HIV/HCV-coinfected patients, and all eligible patients should be offered treatment.     

Transcatheter aortic valve replacement for native aortic valve regurgitation as a bridge to liver transplantation

Coexistence of end‐stage liver disease (ESLD) and severe valvular heart disease conveyed substantial risk for patients, oftentimes leading to exclusion from liver transplantation candidacy due to inability to safely offer cardiac surgery prior to transplantation. Several approaches have been described, including performing transplantation and valve surgery concurrently, or in sequence. Both options, however, have associated complications: catastrophic repercussion of peri‐operative coagulopathy and organ dysfunction post‐transplantation, respectively. The introduction of transcatheter procedures offered a safer alternative for high‐risk patients; however, its recognized indications remained limited. A novel approach to this surgical dilemma by performing transcatheter aortic valve replacement (TAVR) for severe native aortic valve regurgitation in a patient on the liver transplant list has been presented. The procedure proved to be an effective management for the aortic valve insufficiency, improving our patient's hemodynamics in preparation for the subsequent orthotopic liver transplantation (OLT). © 2015 Wiley Periodicals, Inc.     

Kolorektales Karzinom

Over 50,000 new cases of colorectal cancer are diagnosed in Germany every year. About half of these patients will be cured by surgery. The other reoccur or present primarily with advanced disease. Recently, the survival of patients with metastasized disease has been prolonged from about 6 months with best supportive care alone to more than 20 months with combination chemotherapy. Therefore, adequate palliation is reasonable. Irresectable liver metastasis can be treated by locally ablative procedures such as radiofrequency ablation (RFA) or laserinduced thermotherapy (LITT). In the individual case resection of lung or brain metastasis should be discussed. Practitioners have to deal with plenty of supportive opportunities e.g. analgesics, bisphosphonates, central acting drugs, nutrition but also with drug side effects. In centers different endoscopic or interventional radiologic procedures are offered. Considering the variety of therapeutic options, it is prudent to discuss individual treatment plans in an interdisciplinary "tumor board" and involve the practitioners in the decision making.     

Hepatitis D virus and liver transplantation: Indications and outcomes

Hepatitis D virus(HDV) is a dependent virus that relies on hepatitis B virus for its replication and transmission. Chronic hepatitis D is a severe form of viral hepatitis that can result in end stage liver disease. Currently, pegylated interferon alpha is the only approved therapy for chronic HDV infection and is associated with significant side effects. Liver transplantation(LT) is the only treatment option for patients with end-stage liver disease, hepatocellular carcinoma, or fulminant hepatitis due to coinfection with HDV. As LT for HDV and hepatitis B virus coinfection is uncommon in the United States, most data on the long-term impact of LT on HDV are from international centers. In this review, we discuss the indications and results of LT with treatment options in HDV patients.     

Iron and liver fibrosis: Mechanistic and clinical aspects

Liver fibrosis is characterised by excessive deposition of extracellular matrix that interrupts normal liver functionality. It is a pathological stage in several untreated chronic liver diseases such as the iron overload syndrome hereditary haemochromatosis, viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis and diabetes. Interestingly, regardless of the aetiology, iron-loading is frequently observed in chronic liver diseases. Excess iron can feed the Fenton reaction to generate unquenchable amounts of free radicals that cause grave cellular and tissue damage and thereby contribute to fibrosis. Moreover, excess iron can induce fibrosis-promoting signals in the parenchymal and non-parenchymal cells, which accelerate disease progression and exacerbate liver pathology. Fibrosis regression is achievable following treatment, but if untreated or unsuccessful, it can progress to the irreversible cirrhotic stage leading to organ failure and hepatocellular carcinoma, where resection or transplantation remain the only curative options. Therefore,understanding the role of iron in liver fibrosis is extremely essential as it can help in formulating iron-related diagnostic, prognostic and treatment strategies. These can be implemented in isolation or in combination with the current approaches to prepone detection, and halt or decelerate fibrosis progression before it reaches the irreparable stage. Thus, this review narrates the role of iron in liver fibrosis. It examines the underlying mechanisms by which excess iron can facilitate fibrotic responses. It describes the role of iron in various clinical pathologies and lastly,highlights the significance and potential of iron-related proteins in the diagnosis and therapeutics of liver fibrosis.     

The liver biopsy in chronic hepatitis C: a view from the other side of the microscope

The liver biopsy has long been the gold standard for the evaluation of the state of liver disease in patients with chronic hepatitis C. Although a liver biopsy continues to be a recommended part of the work-up of this disease, its routine use is challenged by the increasing effectiveness of therapy and by surrogate biochemical tests that give information about the stage of disease. Nevertheless, recent studies have shown that histological features other than stage may have predictive value for disease progression and therapeutic response to interferon-based regimens. Pathologists can increase the relevance and utility of the liver biopsy in chronic hepatitis C by the systematic reporting of steatosis and iron accumulation in addition to stage and grade, and by identifying certain potential confounding liver diseases, such as steatohepatitis and hereditary hemochromatosis. Clinicians can then make best use of the information derived from the liver biopsy to help them advise patients on the natural history of their disease and the therapeutic options that are available.     

Therapie des hepatozellulären Karzinoms

Today, hepatocellular carcinoma (HCC) represents the leading cause of death in patients with liver cirrhosis; in most western countries the incidence is also expected to increase further. Due to insufficient surveillance of patients at risk, most cases are diagnosed in an intermediate to advanced stage, leading—together with the underlying liver cirrhosis—to limited therapeutic options and a dismal prognosis. Therefore, classification according to stage and interdisciplinary treatment decisions in experienced centers are of paramount importance to provide an individualized treatment plan when considering potentially curative (resection, liver transplantation, local ablation) and palliative (transarterial approaches, sorafenib) treatment options. There is hope that the prognosis of patients with HCC can be improved in the near future by better prevention, stringent surveillance, multimodality treatment approaches, and an expansion of personalized medicine.     

Liver cirrhosis: Child-Pugh grading of cases seen in Nigeria

Child-Pugh grading is an important determinant of treatment options, surgical interventions and prognosis in chronic liver disease. Sixty-four liver cirrhosis patients (49 men, 15 women) seen at Ile-Ife, Nigeria were graded according to the Child-Pugh parameters. Only one (1.6%) was in Class A, while 21 (32.8%) and 42 (65.6%) were in Classes B and C, respectively. Thirty-four either had coagulopathy or were already in encephalopathy at the time of presentation. Hepatitis B virus-associated disease was present in 64% of the patients. Most Nigerian cirrhosis patients present with very advanced disease; they are thus poor-risk candidates for diagnostic procedures and surgery. Efforts should be intensified at making the diagnosis at a much earlier stage and universal immunization with the hepatitis B vaccine should be commenced to reduce the incidence of HBV-related chronic liver disease in Nigeria.     

An update and our experience with metastatic liver disease

Metastatic liver disease remains a challenging and life-threatening clinical situation with an obscure and dismal prognosis and outcome. The liver is the most common site of metastatic spread of colorectal cancer and nearly half of the patients with colorectal cancer ultimately develop liver metastasis during the course of their diseases. Death from colorectal cancer is often a result of liver metastases. Over half of these patients die from their metastatic liver diseases. At the time of diagnosis, hepatic metastases are present in 15-25% of patients, and another 25-50% will develop metachronous liver metastases within 3 years following resection of the primary tumor. Over the last decade, there have been tremendous advances in the treatment of metastatic liver disease. Hepatic resection still remains the gold standard for the treatment of metastatic lesions which are amenable to surgery. Unfortunately, up to 40 percent of patients are identified as having additional disease at the time of exploration, and 20 percent are found to be unresectable. Regional therapies such as radiofrequency ablation, microwave ablation and cryotherapy may be offered to patients with isolated unresectable metastases. Other options like hepatic artery chemotherapy and chemoembolization, portal vein embolization and immunotherapy also play a vital role in management of metastatic liver disease when used in combination with other therapies. This article reviews the history of metastatic liver disease, epidemiology, diagnosis and various treatment modalities available for liver metastases along with our experience in management of advance metastatic liver disease.     

Osteoporosis and fractures in liver disease: Relevance,pathogenesis and therapeutic implications

It is being increasingly recognized that patients with liver disease develop bone loss that can be severe enough to lead to atraumatic fractures and thus markedly diminish life quality and expectancy. The estimated prevalence for liver-related osteoporosis is between 20-420/100000 of the general population, and fractures between 60-880/100000. It should be kept in mind that up to 40% of patients with chronic liver disease may experience a fracture. The pathogenic mediators include fibronectin, insulin like growth factor-I, and various cytokines, but decreased vitamin D and/or treatment with corticosteroids contribute to worsening bone health. Despite the advances in bone biology that have shed some light on the pathogenesis of this bone loss, treatment options remain nonspecific and tightly linked to treatments of other forms of osteoporosis. Thus, treatment should include calcium and vitamin D supplementation in all patients with chronic liver disease. Therapy with bisphosphonates should be considered, especially in patients receiving corticosteroids. This review focuses on the prevalence of this entity as well as the evidence available with regard to the pathogenesis of bone loss in liver disease, the diagnostic steps required in all patients, and the therapeutic options available.     

Neoadjuvant and adjuvant therapy in relation to surgery for colorectal liver metastases

Liver resection is associated with prolonged survival in patients with colorectal liver metastases. At diagnosis, 15-20% of patients have resectable colorectal liver metastases whereas other patients have too advanced disease to enable surgical treatment and receive chemotherapy. In patients undergoing resection of colorectal liver metastases, disease relapse occurs in up to 70%. Therefore, a combined approach including preoperative or postoperative chemotherapy or both has been tested to improve outcome after surgery. In patients with unresectable colorectal liver metastases, chemotherapy is initially the sole treatment option. The considerable improvement of the efficacy of anticancer agents has contributed to increase the response rate in patients with advanced colorectal cancer. In case of major response to chemotherapy, surgery with curative intent can be offered to patients with initially unresectable liver metastases.     

Hepatocellular carcinoma: From diagnosis to treatment

Hepatocellular carcinoma(HCC) is the sixth most prevalent malignancy worldwide and is a rising cause of cancer related mortality. Risk factors for HCC are well documented and effective surveillance and early diagnosis allow for curative therapies. The majority of HCC appears to be caused by cirrhosis from chronic hepatitis B and hepatitis C virus. Preventive strategies include vaccination programs and anti-viral treatments.Surveillance with ultrasonography detects early stage disease and improves survival rates. Many treatment options exist for individuals with HCC and are determined by stage of presentation. Liver transplantation is offered to patients who are within the Milan criteria and are not candidates for hepatic resection. In patients with advanced stage disease, sorafenib shows some survival benefit.     

Management of stage Ⅳ rectal cancer： Palliative options

Approximately 30% of patients with rectal cancer present with metastatic disease. Many of these patients have symptoms of bleeding or obstruction. Several treatment options are available to deal with the various complications that may afflict these patients. Endorectal stenting, laser ablation, and operative resection are a few of the options available to the patient with a malignant large bowel obstruction. A thorough understanding of treatment options will ensure the patient is offered the most effective therapy with the least amount of associated morbidity. In this review, we describe various options for palliation of symptoms in patients with metastatic rectal cancer. Additionally, we briefly discuss treatment for asymptomatic patients with metastatic disease.     

Minimally invasive image-guided therapy of primary and metastatic pancreatic cancer

Pancreatic cancer is a challenging malignancy with limited treatment options and poor life expectancy. The only curative option is surgical resection, but only 15%-20% of patients are resectable at presentation because more than 50% of patients has distant metastasis at diagnosis and the rest of them has locally advanced pancreatic cancer (LAPC). The standard of care first line treatment for LAPC patients is chemotherapy with or without radiation therapy. Recent developments in minimally invasive ablative techniques may add to the treatment armamentarium of LAPC. There are increasing number of studies evaluating these novel ablative techniques, including radiofrequency ablation, microwave ablation, cryoablation and irreversible electroporation. Most studies which included pancreatic tumor ablation, demonstrated improved overall survival in LAPC patients. However, the exact protocols are yet to set up to which stage of the treatment algorithm ablative techniques can be added and in what kind of treatment combinations. Patients with metastatic pancreatic cancer has dismal prognosis with 5-year survival is only 3%. The most common metastatic site is the liver as 90% of pancreatic cancer patients develop liver metastasis. Chemotherapy is the primary treatment option for patients with metastatic pancreatic cancer. However, when the tumor is not responding to chemotherapy or severe drug toxicity develops, locoregional liver-directed therapies can provide an opportunity to control intrahepatic disease progression and improve survival in selected patients. During the last decade new therapeutic options arose with the advancement of minimally invasive technologies to treat pancreatic cancer patients. These new therapies have been a topic of increasing interest due to the severe prognostic implications of locally advanced and metastatic pancreatic cancer and the low comorbid risk of these procedures. This review summarizes new ablative options for patients with LAPC and percutaneous liver-directed therapies for patients with liver-dominant metastatic disease.