S-1 maintenance therapy in Caucasian patients with metastatic esophagogastric adenocarcinoma-final results of the randomized AIO MATEO phase II trial.

PURPOSE: Platinum-fluoropyrimidine combinations are standard of care for treatment of metastatic esophagogastric adenocarcinoma. The optimal duration of first-line chemotherapy is unknown, however, and maintenance strategies have not yet been established. DESIGN: MATEO is an international randomized phase II trial exploring efficacy and safety of S-1 maintenance therapy in human epidermal growth factor receptor 2 (HER2)-negative advanced esophagogastric adenocarcinoma. After 3 months of first-line platinum-fluoropyrimidine-based induction therapy, patients without progression were randomized in a 2 : 1 allocation to receive S-1 monotherapy (arm A) or to continue combination chemotherapy (arm B). The primary objective was to show non-inferiority of overall survival in the S-1 maintenance group. Progression-free survival, adverse events, and quality of life were secondary endpoints. RESULTS: From 2014 to 2019, 110 and 55 patients were randomized in arm A and arm B, respectively (recruitment closed prematurely). Median overall survival from randomization was 13.4 months for arm A and 11.4 months for arm B [hazard ratio 0.97 (80% confidence interval 0.76-1.23), P = 0.86]. Median progression-free survival from randomization was 4.3 and 6.1 months for arm A versus arm B, respectively [hazard ratio 1.10 (80% confidence interval 0.86-1.39), P = 0.62]. Patients in arm A had numerically fewer treatment-related adverse events (84.9% versus 93.9%) and significantly less peripheral sensory polyneuropathy ≥grade 2 (9.4% versus 36.7%). CONCLUSIONS: S-1 maintenance following platinum-based induction therapy leads to non-inferior survival outcomes compared with the continuation of platinum-based combination. Toxicity patterns favor a fluoropyrimidine maintenance strategy. These data challenge the continued use of platinum combination chemotherapy after response to 3 months induction therapy in patients with advanced human epidermal growth factor receptor 2-negative esophagogastric adenocarcinoma.

Afatinib plus gemcitabine versus gemcitabine alone as first-line treatment of metastatic pancreatic cancer: The randomised, open-label phase II ACCEPT study of the Arbeitsgemeinschaft Internistische Onkologie with an integrated analysis of the 'burden of therapy' method.

BACKGROUND: Targeting the epidermal growth factor receptor pathway remains controversial in pancreatic cancer. Afatinib is an oral irreversible ErbB family blocker approved in non-small-cell lung cancer. This open-label, multicenter, randomised phase II trial evaluated gemcitabine plus afatinib (Gem/afatinib) versus gemcitabine (Gem) alone as first-line treatment for metastatic pancreatic cancer. PATIENTS AND METHODS: Patients were randomised in a 2:1 ratio to either Gem (1000 mg/m2 weekly for three weeks followed by one week of rest, repeated every four weeks) and afatinib (40 mg orally once daily) or Gem alone. Overall survival (OS) was the primary study end-point. The novel BOTh©™ methodology was implemented to derive a quantitative estimate for the 'Burden of Therapy/Toxicity' (BOTh) for each patient on every day during the clinical study. RESULTS: One hundred nineteen patients from 25 centres were randomised, 79 patients for Gem/afatinib and 40 for Gem. Median OS was 7.3 months in the Gem/afatinib arm versus 7.4 months in the Gem-alone arm (hazard ratio [HR]: 1.06, p = 0.80). Median progression-free survival was identical in both arms (3.9 months versus 3.9 months, HR: 0.85, p = 0.43). Adverse events were more frequent in the Gem/afatinib arm, especially diarrhoea (71% vs. 13%) and skin rash (65% vs. 5%). The BOTh©™ analysis revealed a significantly higher burden of toxicity in the combination arm (p = 0.0005). CONCLUSION: The addition of afatinib to Gem did not improve treatment efficacy and was more toxic. The BOTh©™ methodology allowed a detailed insight into the course of treatment-related adverse events over the study period. The trial was registered at clinicaltrials.gov (NCT01728818) and Eudra-CT (2011-004063-77).

Treatment decisions in metastatic colorectal cancer - Beyond first and second line combination therapies.

Median overall survival (OS) of patients with metastatic colorectal cancer (mCRC) has reached up to 30months in recent clinical trials of first line therapies. Following disease progression after the standard in both, 1st and 2nd line, combination chemotherapy with monoclonal antibodies, many patients maintain a good performance status and a significant proportion is motivated to undergo further therapy. Choices of treatment beyond the second line setting for mCRC are therefore becoming increasingly important. New options have entered the therapeutic field recently: Regorafenib is a multikinase inhibitor approved for mCRC patients who have progressed on chemotherapy (including fluoropyrimidines, irinotecan, and oxaliplatin), plus VEGF inhibitor(s) and - if RAS wild-type - an anti-EGFR inhibitor. Regorafenib significantly improved OS, compared to placebo, in two phase III trials (CORRECT and CONCUR) in mCRC patients. Trifluridine/Tipiracil, an oral fluoropyrimidine, also resulted in significantly improved OS when compared to placebo in the phase III RECOURSE trial, which was conducted in a similar patient population to CORRECT. Reintroduction of previously administered therapy is another valid and commonly used approach, especially for those regimens which were discontinued before progression, e.g. if associated with cumulative toxicities, such as peripheral neuropathy or due to treatment breaks. Re-challenge of drugs to which patients developed resistance is also feasible although evidence for this strategy is limited.

Treatment with Antiangiogenic Drugs in Multiple Lines in Patients with Metastatic Colorectal Cancer: Meta-Analysis of Randomized Trials.

Background. In metastatic colorectal cancer (mCRC), continuing antiangiogenic drugs beyond progression might provide clinical benefit. We synthesized the available evidence in a meta-analysis. Patients and Methods. We conducted a meta-analysis of studies investigating the use of antiangiogenic drugs beyond progression. Eligible studies were randomized phase II/III trials. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints were the impact of continuing antiangiogenic drugs (i) in subgroups, (ii) in different types of compounds targeting the VEGF-axis (monoclonal antibodies versus tyrosine kinase inhibitors), and (iii) on remission rates and prevention of progression. Results. Eight studies (3,668 patients) were included. Continuing antiangiogenic treatment beyond progression significantly improved PFS (HR 0.64; 95%-CI, 0.55-0.75) and OS (HR 0.83; 95%-CI, 0.76-0.89). PFS was significantly improved in all subgroups with comparable HR. OS was improved in all subgroups stratified by age, gender, and ECOG status. The rate of patients achieving at least stable disease was improved with an OR of 2.25 (95%-CI, 1.41-3.58). Conclusions. This analysis shows a significant PFS and OS benefit as well as a benefit regarding disease stabilization when using antiangiogenic drugs beyond progression in mCRC. Future studies should focus on the optimal sequence of administering antiangiogenic drugs.

Economic outcomes of sequences which include monoclonal antibodies against vascular endothelial growth factor and/or epidermal growth factor receptor for the treatment of unresectable metastatic colorectal cancer.

BACKGROUND: Patients with unresectable, metastatic colorectal cancer with wild type Kirsten ras mutational status are eligible for sequential treatments which include monoclonal antibodies as first line (1L), second line (2L), or third line (3L) regimens. OBJECTIVE: To compare the economic outcomes of different sequences which include monoclonal antibodies for the treatment of unresectable metastatic colorectal cancer. METHODS: Individual drug regimens for 1L, 2L, and 3L treatments were compiled according to the clinical studies in the Summary of Product Characteristics for monoclonal antibodies. They were combined into plausible treatment sequences. Health outcomes were approximated using additive median PFS benefit, and economic outcomes were calculated with a treatment sequencing costing tool. Limitations of the analysis include the clinical trial data sources, cost assumptions, and the additive PFS approach. RESULTS: Seventeen sequences were evaluated. Results of the analysis show that sequences including 1L anti-EGFRs generally have relatively low-to-medium health outcomes at the highest comparative sequence costs compared to sequences including 2L anti-EGFRs, which have lower health outcomes at the lowest cost. Sequences including 3L anti-EGFRs (sequential bevazicumab-based 1L and 2L) have the highest health outcomes, with potential cost savings of €5972-€11,676 if replacing 2L anti-EGFRs or an additional cost of €5909-€12,708 if replacing 1L anti-EGFR regimens. CONCLUSION: Clinical sequences consisting of 1L and 2L line bevacizumab followed by 3L anti-EGFR potentially yield the greatest health outcomes associated with a reasonable trade-off in additional cost when replacing 1L anti-EGFRs and are potentially cost-saving if replacing 2L anti-EGFRs, per patient per lifetime. To maximize health outcomes, optimal sequences include anti-EGFRs as 3L regimen, with an approximately equivalent trade-off in costs between the most costly (anti-EGFR 2L) and least costly (anti-EGFR 1L) sequences.

Bevacizumab plus chemotherapy continued beyond first progression in patients with metastatic colorectal cancer previously treated with bevacizumab plus chemotherapy: ML18147 study KRAS subgroup findings.

BACKGROUND: ML18147 evaluated continued bevacizumab with second-line chemotherapy for patients with metastatic colorectal cancer (mCRC) progressing after the standard first-line bevacizumab-containing therapy. PATIENTS AND METHODS: Evaluating outcomes according to tumor Kirsten rat sarcoma virus oncogene (KRAS) status was an exploratory analysis. KRAS data were collected from local laboratories (using their established methods) and/or from a central laboratory (mutation-specific Scorpion amplification-refractory mutation system). No adjustment was made for multiplicity; analyses were not powered to detect statistically significant differences. RESULTS: Of 820 patients, 616 (75%) had unambiguous KRAS data; 316 (51%) had KRAS wild-type tumors and 300 (49%) had mutant KRAS tumors. The median progression-free survival (PFS) was 6.4 months for bevacizumab plus chemotherapy and 4.5 months for chemotherapy [P < 0.0001; HR = 0.61; 95% confidence interval (CI): 0.49-0.77] for wild-type KRAS and 5.5 and 4.1 months, respectively (P = 0.0027; HR = 0.70; 95% CI: 0.56-0.89) for mutant KRAS. The median overall survival (OS) was 15.4 and 11.1 months, respectively (P = 0.0052; HR = 0.69; 95% CI: 0.53-0.90) for wild-type KRAS and 10.4 versus 10.0 months, respectively (P = 0.4969; HR = 0.92; 95% CI: 0.71-1.18) for mutant KRAS. In both analyses, no treatment interaction by KRAS status was observed (PFS, P = 0.4436; OS, P = 0.1266). CONCLUSIONS: Bevacizumab beyond first progression represents an option for patients with mCRC treated with bevacizumab plus standard first-line chemotherapy, independent of KRAS status.

Capecitabine/irinotecan or capecitabine/oxaliplatin in combination with bevacizumab is effective and safe as first-line therapy for metastatic colorectal cancer: a randomized phase II study of the AIO colorectal study group.

BACKGROUND: This randomized phase II trial investigated the efficacy and safety of capecitabine/oxaliplatin (CapOx) plus bevacizumab and dose-modified capecitabine/irinotecan (mCapIri) plus bevacizumab as first-line therapy in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Patients received bevacizumab 7.5 mg/kg with oxaliplatin 130 mg/m(2)/day 1 plus capecitabine 1000 mg/m(2) bid/days 1-14 or with irinotecan 200 mg/m(2)/day 1 plus capecitabine 800 mg/m(2) bid/days 1-14 both every 21 days. The primary end point was 6 months progression-free survival (PFS). RESULTS: A total of 255 patients were enrolled. The intent-to-treat population comprised 247 patients (CapOx-bevacizumab: n = 127; mCapIri-bevacizumab: n = 120). The six-month PFS rates were 76% (95% CI, 69%-84%) and 84% (95% CI, 77%-90%). Median PFS and OS were 10.4 months (95% CI, 9.0-12.0) and 24.4 months (95% CI, 19.3-30.7) with CapOx-bevacizumab, and 12.1 months (95% CI, 10.8-13.2) and 25.5 months (95% CI, 21.0-31.0) with mCapIri-bevacizumab. Grade 3/4 diarrhea as predominant toxic effect occurred in 22% of patients with CapOx-bevacizumab and in 16% with mCapIri-bevacizumab. CONCLUSIONS: Both, CapOx-bevacizumab and mCapIri-bevacizumab, show promising activity and an excellent toxic effect profile. Efficacy is in the range of other bevacizumab-containing combination regimen although lower doses of irinotecan and capecitabine were selected for mCapIri.

Combination of conservative and interventional therapy strategies for intra- and extrahepatic cholangiocellular carcinoma: a retrospective survival analysis.

Background. Due to the predominantly advanced stage at the time of diagnosis treatment of cholangiocarcinoma is difficult. Apart from surgical resection, interventional treatment strategies are increasingly used in advanced stage tumours. The aim of the study was a retrospective comparison of the effect of the various forms of treatment on morbidity and mortality. Method. A total of 195 patients, received either chemotherapy or a combination of photodynamic therapy (PDT) or transarterial chemoembolization (TACE) and chemotherapy. Results. The median survival rate for all patients was 15.6 months, 50.8% were still alive 1 year after diagnosis. Patients, who had previously undergone surgery, survived 17.1 months longer than those without surgical treatment (P < .01). Chemotherapy prolonged the survival by 9.2 months (P = .47). Palliative patients under combination of chemotherapy and PDT survived on average 1.8 months longer (P = .28), with chemotherapy and TACE 9.8 months longer (P = .04) compared to chemotherapy alone. Conclusions. It appears that surgical treatment and chemotherapy combined with PDT or TACE may prolong survival.

Peripapillary duodenal varices as a rare cause of severe bleeding in a patient with no other signs of portal hypertension--successful endoscopic treatment with cyanoacrylate injection.

Duodenal varices (DVs) are a rare cause of upper gastrointestinal bleeding and rather suspected in patients with portal hypertension. Bleeding DVs are difficult to manage and often fatal due to delayed diagnosis. We report on a 71-year-old patient with massive upper gastrointestinal haemorrhage, who did not show any clinical signs of portal hypertension; however, he had a history of duodenal segmental resection 8 years before. The source of bleeding could not be detected with different imaging methods such as angiography and computed tomography. Upper gastrointestinal endoscopy finally revealed DVs, which were located just adjacent to the papilla. After endoscopic injection therapy with n-butyl 2-cyanoacrylate the bleeding stopped immediately and the patient soon stabilised. Despite the peripapillar localisation no signs of pancreatitis or cholestasis occurred; during 10-month follow-up a marked regression of the varices without further signs of variceal bleeding was observed.

Cetuximab with irinotecan, folinic acid and 5-fluorouracil as first-line treatment in advanced gastroesophageal cancer: a prospective multi-center biomarker-oriented phase II study.

BACKGROUND: Cetuximab plus irinotecan/folinic acid/5-fluorouracil (5-FU) (IF) was evaluated as first-line treatment of patients with advanced gastric cancer and gastroesophageal junction tumors. Preplanned analyses of the influence of tumor biomarkers on treatment outcome were carried out. PATIENTS AND METHODS: Patients received weekly cetuximab (400 mg/m(2) on day 1, subsequently 250 mg/m(2)) plus irinotecan (80 mg/m(2)) and a 24-hour continuous infusion of folinic acid (200 mg/m(2)) and 5-FU (1500 mg/m(2)) on days 1, 8, 15, 22, 29 and 36 of a 50-day cycle, until progressive disease (PD). RESULTS: The most common grade 3/4 toxic effects in 49 patients were diarrhea (15%) and skin toxic effects (14%). In 48 assessable patients, the overall response rate was 46% and disease control rate was 79%. Median progression-free survival (PFS) and overall survival (OS) was 9.0 months [95% confidence interval (CI) 7.1-15.6] and 16.5 months (95% CI 11.7-30.1), respectively. Tumor response was more common than nonresponse in epidermal growth factor receptor-expressing tumors (P = 0.041). Tumor PTEN expression was associated with longer PFS (P = 0.035) and OS (P = 0.0127) than no PTEN expression. CONCLUSION: Cetuximab plus IF was well tolerated and efficacy data were encouraging. This treatment combination and the role of selected biomarkers are under investigation in the ongoing phase III EXPAND trial.

[Multimodality therapy of colorectal cancer]. / Multimodale Therapie des kolorektalen Karzinoms.

Adjuvant chemotherapy for resected stage III colon cancer is indicated for all patients, including elderly patients >70 years. In general, adjuvant oxaliplatin-fluoropyrimidine chemotherapy should be started within 6 weeks after tumor resection and should be given for a period of 6 months. However, patients aged >70 should receive fluoropyrimidine mono-chemotherapy. This mono-therapy, but not an oxaliplatin-based combination, can also be considered for patients with standard risk stage II tumors without microsatellite instability. In stage II patients with a high risk constellation adjuvant oxaliplatin-fluoropyrimidine combination therapy should be considered. Patients with stage II and III rectal cancer require neoadjuvant radiochemotherapy with fluoropyrimidine followed by adjuvant fluoropyrimidine treatment. There is no role for the use of VEGF- or EGFR-antibodies in the adjuvant therapy of colon cancer or in neoadjuvant therapy of rectal cancer. The prognosis of patients with primary resectable colorectal liver metastases may be improved by adjuvant or perioperative chemotherapy, while neoadjuvant systemic chemotherapy frequently facilitates potential curative resection of initially non-resectable liver metastases.

[Differentiated therapy of liver tumors]. / Differenzialtherapie von Lebertumoren.

Focal nodular hyperplasia is a polyclonal hyperplasia of liver cells as a result of locally enhanced blood flow because of vessel malformations. Only symptomatic FNH is an indication for resection or enucleation. In contrast to FNH growth of adenoma is dependent on sexual hormones. Solitary HNFalpha-inactivated and inflammatory adenomas larger than 5 cm should be removed because of risk of tumor rupture or bleeding, while beta-catenin mutated adenomas should be surgically removed at any stage because of risk of malignant transformation. The prognosis of patients with HCC is dependent on the tumor stage, but also on the liver function. Resection is the treatment of choice for HCC in patients without liver cirrhosis. Patients with liver cirrhosis and early HCC without extrahepatic metastasis can be successfully treated by liver transplantation. If transplantation is not possible these tumors should be removed by local percutaneous ablation. Transarterial chemoembolization is an effective treatment for more advanced HCC in patients with good liver function. Studies showed that the multikinase inhibitor sorafenib significantly improves survival of patients with advanced or metastatic HCC in child A cirrhosis. The only curative option for patients with intrahepatic cholangiocarcinomas is surgical resection. Patients with unresectable cholangiocarcinomas should be treated with a chemotherapy consisting of Gemcitabine-Cisplatin-combination.

VSV virotherapy improves chemotherapy by triggering apoptosis due to proteasomal degradation of Mcl-1.

Overexpression of myeloid cell leukemia 1 protein (Mcl-1), an anti-apoptotic B-cell lymphoma 2 (Bcl-2) family member, contributes to chemotherapy resistance of tumors. The short half-life of Mcl-1 makes it an interesting target for therapeutic agents that negatively interfere with cellular protein biosynthesis, such as oncolytic viruses. Vesicular Stomatitis Virus (VSV) has been established as the oncolytic virus that efficiently disrupts de novo protein biosynthesis of infected cells. Here, we show that after VSV infection, Mcl-1 protein levels rapidly declined, whereas the expression of other members of the Bcl-2 family remained unchanged. Mcl-1 elimination was a consequence of proteasomal degradation, as overexpression of a degradation-resistant Mcl-1 mutant restored Mcl-1 levels. Mcl-1 rescue inhibited apoptosis and thereby confirmed that Mcl-1 downregulation contributes to VSV-induced apoptosis. In vitro, VSV virotherapy in combination with chemotherapy revealed an enhanced therapeutic effect compared with the single treatments, which could be reverted by Mcl-1 rescue or RNA interference (RNAi)-mediated knockdown of pro-apoptotic Bax and Bak proteins. Finally, in a tumor mouse model, combinations of doxorubicin and VSV showed a superior therapeutic efficacy compared with VSV or doxorubicin alone. In summary, our data indicate that VSV virotherapy is an attractive strategy to overcome tumor resistance against conventional chemotherapy by elimination of Mcl-1.

[Gastrointestinal oncology - therapy update 2008 / 2009]. / Gastrointestinale Onkologie - Therapieupdate 2008 / 2009.

As a consequence of recent studies the treatment of gastrointestinal cancers has become challenging and is undergoing constant changes on the basis of the results of new trials. The steering committee of the working group on gastrointestinal cancers of the Deutsche Gesellschaft für Verdauungs- und Stoffwechselkrankheiten has decided to summarise and present recent updates of the current treatment guidelines and recommendations for the most relevant gastrointestinal malignancies. In this review we have included recent findings from large trials on esophageal, gastric, pancreatic, cholangiocellular and liver cancers, as well as colorectal cancers, neuroendocrine tumours and lymphomas. This includes an update on the combination with novel targeted agents and the introduction of potential predictive biomarkers in the selection of the appropriate treatment strategy.

[Systemic treatment of liver and biliary tumors]. / Systemische Therapie von Leber- und Gallenwegstumoren.

Hepatocellular carcinoma (HCC) is generally difficult to treat. This is primarily due to the reduced liver function of most patients and the low sensitivity of liver cancer cells to chemotherapy. This has been demonstrated in many clinical trials. Molecular therapies might represent an improvement in the systemic treatment of patients with HCC. In addition to anti-angiogenic drugs, compounds which interfere with specific signal transduction cascades have shown promising results in smaller trials. There are only limited numbers of studies about the systemic treatment options for biliary cancers. To date, the best response rates have been achieved with combination chemotherapies containing platinum analogues and gemcitabine. In the absence of larger clinical phase III trials, no standard chemotherapy for biliary cancers exists today.

Chemoocclusion vs chemoperfusion for treatment of advanced hepatocellular carcinoma: a randomised trial.

AIMS: Transarterial chemoembolization (TACE) can be associated with considerable toxicity and treatment-associated mortality. Transient transarterial chemoocclusion (TACO) using degradable starch microspheres (DSM) has been proposed as a potentially safer alternative while maintaining anti-tumour efficiency. In a randomised phase II trial TACO was compared to transarterial chemoperfusion without DSM (TACP). METHODS: Seventy-four patients with advanced HCC were randomised to two treatment arms: (i) TACO (600-1200 mg DSM) and (ii) TACP. In both arms regional chemotherapy consisted of cisplatin (100 mg/m2) and doxorubicin (60 mg/m2). Both arms were corresponding in terms of age, gender, liver performance state, and tumour-stage. A maximum of six treatment cycles was applied in monthly intervals. Follow-up was performed in terms of tumour response, time to progression, survival and quality of life. RESULTS: Tumour response rates did not differ significantly between the two treatment arms, however, there was a tendency towards higher response rates in the TACO arm (TACO vs TACP): partial response: 26 vs 9%, stable disease: 41 vs 55%, progressive disease: 33 vs 36%. Time to tumour progression (32 vs 27 weeks), and overall survival (60 vs 69 weeks) were not significantly different. Grade 4 adverse events were rare in both arms and treatment-associated mortality was not observed. In addition, there was no significant difference in terms of quality of life under therapy (EORTC). CONCLUSION: TACO with DSM did not improve response or survival significantly compared to TACP in advanced non-resectable HCC.

Tumour necrosis factor related apoptosis inducing ligand (TRAIL) induces hepatic steatosis in viral hepatitis and after alcohol intake.

BACKGROUND AND AIMS: Tumour necrosis factor related apoptosis inducing ligand (TRAIL) induces apoptosis in transformed cells and is considered as an agent for cancer therapy. As there is evidence that TRAIL is also essential for apoptosis in animal models of liver injury, we investigated the role of TRAIL in viral hepatitis and after alcohol consumption. METHODS: Expression of TRAIL was determined by western blot analysis in the liver of patients with chronic hepatitis C virus (HCV) infection as well as in experimental acute adenoviral hepatitis and after alcohol intake in the liver of mice. To investigate the effect of FasL and TRAIL expression, we used low dose adenoviral gene transfer. Apoptosis and steatosis were assessed by TUNEL and fat red staining, and by caspase assays. RESULTS: TRAIL was overexpressed in the liver of patients with HCV associated steatosis while acute adenoviral hepatitis resulted in upregulation of TRAIL-DR5. In contrast with FasL, TRAIL expression was harmless to healthy livers. However, in virally infected livers, TRAIL expression induced apoptosis and steatosis whereas expression of FasL only resulted in apoptosis of hepatocytes without steatosis. After alcohol intake, TRAIL expression led to hepatic steatosis, without apoptosis of hepatocytes, indicating that TRAIL mediated apoptosis and steatosis may be independently modulated after viral infection and alcohol intake. In viral hepatitis and after alcohol intake, Ad-TRAIL mediated steatosis can be inhibited by injection of a neutralising TRAIL antibody. CONCLUSIONS: We identified TRAIL as a new mediator of hepatic steatosis in viral hepatitis and after alcohol intake. Consequently, TRAIL mediated hepatotoxicity has to be considered in patients with viral hepatitis and alcoholic liver disease.

Survival rate in patients with hepatocellular carcinoma: a retrospective analysis of 389 patients.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. However, treatment options are limited and often inefficient. The aim of this study was to determine current survival rates for patients diagnosed with HCC and to identify prognostic factors, which will help in choosing optimal therapies for individual patients. A retrospective analysis of medical records was performed on 389 patients who were identified through the central tumour registry at our institution from 1998 to 2003. Clinical parameters, treatments received and survival curves from time of diagnosis were analysed. Overall median survival was 11 months. Liver cirrhosis was diagnosed in 80.5% of all patients. A total of 170 patients received transarterial chemoembolisation (TACE) and/or percutaneous ethanol injections (PEI) with a median survival rate of 16 months for patients receiving TACE, 11 months for patients receiving PEI and 24 months for patients receiving TACE followed by PEI. Independent negative prognostic parameters for survival were the presence of portal vein thrombosis, advanced liver cirrhosis (Child-Pugh score B or C) and a score of >2. This study will help to estimate survival rates for patients with HCC according to their clinical status at diagnosis and the treatments received.