Kerstin Schütte

Hepatocellular Carcinoma – Epidemiological Trends and Risk Factors

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide with about 600,000 patients dying from the disease annually. In 70–90%, HCC develops on the background of chronic liver cirrhosis or inflammation. Risk factors and etiologies vary among geographical regions. In regions with a high incidence the majority of cases are related to HBV and HCV hepatitis. In developed countries, in addition to virus-related HCC, high consumption of alcohol as well as non-alcoholic fatty liver disease often in the context of metabolic syndromes are the prevalent causes. Improvement in clinical management of patients with liver cirrhosis and the control of related complications are the key for the rising incidence of HCC. This review gives an overview on epidemiological trends and risk factors and their mechanisms involved in the hepatocarcinogenesis. Knowledge of these factors will help to improve current concepts for prevention, screening and treatment of this disease.

Markers for predicting severity and progression of acute pancreatitis.

Several tools have been developed for severity stratification in acute pancreatitis. They include single biochemical markers, imaging methods, and complex scoring systems, all of which aim at an early detection of severe acute pancreatitis to optimise monitoring and treatment of patients as early as possible. Among single biochemical markers, C-reactive protein (CRP) remains the most useful. Despite its delayed increase, peaking not earlier than 72 h after the onset of symptoms, it is accurate and widely available. Many other markers have been evaluated for their usefulness, and for some of them very promising data could be shown. Among them interleukin 6 seems to be the most promising parameter for use in clinical routine. For the detection of pancreatic infection, procalcitonin is the most sensitive, and can be used as an indicator for the need for fine-needle aspiration of pancreatic necrosis. Regarding imaging, contrast-enhanced computed tomography is still the reference method for the detection of necrotising acute pancreatitis. Pancreatitis-specific scoring systems have been shown to be of value for the prediction of severity and progression of acute pancreatitis, but cannot be applied any earlier than 48 h after admission to hospital. The APACHE-II score has not been developed specifically for acute pancreatitis and is rather complex to assess, but has been proven to be an early and reliable tool. Indication, timing and consequences of the methods applied need to be carefully considered and incorporated into clinical assessments to avoid costs and harm to the patient.

Safety and toxicity of radioembolization plus Sorafenib in advanced hepatocellular carcinoma: analysis of the European multicentre trial SORAMIC

The benefits of combined systemic and liver‐directed treatments in inoperable intermediate‐ or advanced‐stage hepatocellular carcinoma (HCC) have yet to be defined. This article presents the planned safety analyses for the first 40 patients randomized to radioembolization with yttrium‐90 (90Y) resin microspheres followed by sorafenib (n = 20) or sorafenib only (n = 20) in the SORAMIC study.

L-Carnitine-supplementation in advanced pancreatic cancer (CARPAN) - a randomized multicentre trial

BackgroundCachexia, a >10% loss of body-weight, is one factor determining the poor prognosis of pancreatic cancer. Deficiency of L-Carnitine has been proposed to cause cancer cachexia.FindingsWe screened 152 and enrolled 72 patients suffering from advanced pancreatic cancer in a prospective, multi-centre, placebo-controlled, randomized and double-blinded trial to receive oral L-Carnitine (4 g) or placebo for 12 weeks. At entry patients reported a mean weight loss of 12 ± 2,5 (SEM) kg. During treatment body-mass-index increased by 3,4 ± 1,4% under L-Carnitine and decreased (−1,5 ± 1,4%) in controls (p < 0,05). Moreover, nutritional status (body cell mass, body fat) and quality-of-life parameters improved under L-Carnitine. There was a trend towards an increased overall survival in the L-Carnitine group (median 519 ± 50 d versus 399 ± 43 d, not significant) and towards a reduced hospital-stay (36 ± 4d versus 41 ± 9d,n.s.).ConclusionWhile these data are preliminary and need confirmation they indicate that patients with pancreatic cancer may have a clinically relevant benefit from the inexpensive and well tolerated oral supplementation of L-Carnitine.

Characterization and prognosis of patients with hepatocellular carcinoma (HCC) in the non-cirrhotic liver

BackgroundHCC predominantly develops in the condition of chronic inflammation that has led to liver cirrhosis. A small proportion of patients with HCC is diagnosed in the non-cirrhotic liver (NCL). Data on patients with HCC in NCL in advanced stages are scarce.MethodsA retrospective analysis was performed comparing 93 patients with HCC in NCL to 571 patients with HCC in liver cirrhosis (LC) with respect to clinical and demographic characteristics. Also factors influencing survival in patients with HCC in NCL were analyzed.ResultsPatients with HCC in NCL were diagnosed at older age and in more advanced tumor stages than patients with LC. More than 25% of patients with HCC in NCL presented with extrahepatic metastases. Only a minority of patients with HCC in NCL lacked any sign of hepatic damage. Risk factors for LC and risk factors for NAFLD are present in the majority of patients with HCC in NCL. The BCLC classification corresponded with the survival of patients with HCC in NCL although the therapeutic options differ from those for patients with liver cirrhosis.ConclusionsIt will be one of the major challenges in the future to awake awareness of carrying a risk of hepatic malignancies in patients with chronic liver diseases apart from liver cirrhosis, especially in NAFLD. Surveillance programs need to be implemented if these are cost-effective.

Causes and Mechanisms in Acute Pancreatitis

Acute pancreatitis (AP) presents clinically with either mild or severe clinical course. There are no effective specific drugs for treatment of AP today. Basic knowledge about pathophysiological processes is the key for the development of novel therapeutic principles. This article provides a review on the pathophysiological mechanisms involved in the early phase of AP.

Malnutrition is a prognostic factor in patients with hepatocellular carcinoma (HCC).

BACKGROUND & AIMS Malnutrition is a common, hence frequently underdiagnosed condition in patients with liver cirrhosis as well as in patients with cancer and has been shown to have a negative impact on survival in these patients. Frequently applied screening tools including anthropometric measurements or laboratory parameters to screen for malnutrition are not suitable for patients with liver cirrhosis with additional pathophysiological mechanisms leading to hypoalbuminemia and edema. Prospective data on the prevalence and prognostic impact of malnutrition in patients with HCC are scarce. METHODS Fifty-one consecutive patients with hepatocellular carcinoma were prospectively enrolled into this study and screened for malnutrition by anthropometric measurements, the MNA score, the NRS score, laboratory work-up, and BIA measurement. The results of the different screening tools were compared to each other and with the BIA assessment and correlated with the outcome of patients. RESULTS The calculation of a body mass index (BMI) was not suitable to identify malnourished patients with HCC. The MNA identified 19, the NRS score 17 patients at a risk for malnutrition. BIA revealed a reduction in relative body cell mass in 12 patients. Univariate Cox regression analyses identified tumor stage, MNA score, and phase angle obtained by BIA as significant factors with influence on survival. Multivariate analyses confirmed the phase angle at a cut-off of 4.8 to be an independent factor. CONCLUSIONS A significant proportion of patients with HCC is malnourished or at risk for malnutrition. Screening questionnaires and BIA measurement are superior to pure anthropometric measurements to identify the condition that negatively influences survival. The phase angle derived from body impedance analysis is an independent prognostic factor in patients with HCC.

Sorafenib Therapy in Patients with Advanced Hepatocellular Carcinoma in Advanced Liver Cirrhosis

Background and Aim: Sorafenib has become the treatment standard for patients with advanced hepatocellular carcinoma (HCC). It is not clear whether patients with advanced liver function impairment (Child B) and patients undergoing additional locoregional therapy may tolerate treatment with sorafenib and benefit. We aimed to evaluate the tolerability and efficiency of sorafenib in patients with advanced HCC and different stages of liver cirrhosis, and in combination with locoregional therapy. Methods: In 50 patients with advanced HCC treated with sorafenib tolerability and efficiency of the therapy with respect to stage of liver cirrhosis, existence of extrahepatic tumor spread, and additional locoregional therapy were evaluated. Results: Fifty patients with advanced HCC were treated with sorafenib, and 13 received additional locoregional therapy. Tolerability of the systemic treatment was moderate in all patients, with no significant differences between the subgroups, while the median survival was better in patients with Child A than Child B cirrhosis. Conclusion: Tolerability and toxicity of a systemic treatment with sorafenib are moderate in patients with liver cirrhosis in Child A or B. Prospective randomized studies are required to evaluate the efficacy and tolerability of combined systemic and locoregional treatment approaches in patients with advanced HCC.

Double-balloon enteroscopy in the diagnosis of suspected isolated Crohn's disease of the small bowel

Diagnosis of Crohns disease (CD) with isolated involvement of the small bowel remains a major challenge. Diagnostic procedures allowing direct insight into the midgut have become available with the introduction of double‐balloon enteroscopy (DBE) and video‐capsule endoscopy (VCE). The aim of the present study was to evaluate the role of DBE in the diagnosis of isolated CD of the small bowel.

The active bacterial assemblages of the upper GI tract in individuals with and without Helicobacter infection

Objective Patients infected with Helicobacter pylori develop chronic gastritis with a subgroup progressing to further complications. The role of microbiota from the oral cavity swallowed with saliva and either transiting the stomach or persisting in the gastric mucosa is uncertain. It is also not known whether the bacterial community differs in luminal and mucosal niches. A key question is whether H. pylori influences the bacterial communities of gastroduodenal niches. Design Saliva, gastric and duodenal aspirates as well as gastric and duodenal biopsies were collected during oesophagogastroduodenoscopy from 24 patients (m:9, f:15, mean age 52.2±SD 14.5 years). RNA was extracted and the V1–V2 region of the retrotranscribed bacterial 16S rRNA amplified and sequenced on the Illumina MiSeq platform. Results Overall, 687 bacterial phylotypes that belonged to 95 genera and 11 phyla were observed. Each individual comprised a unique microbiota composition that was consistent across the different niches. However, the stomach fluid enriched for specific microbiota components. Helicobacter spp were shown to dominate the mucosa-associated community in the stomach, and to significantly influence duodenal and oral communities. Conclusions The detailed analysis of the active global bacterial communities from the five distinct sites of the upper GI tract allowed for the first time the differentiation between host effects and the influence of sampling region on the bacterial community. The influence of Helicobacter spp on the global community structures is striking.