Usage Behaviour and Adoption Criteria for Mobile Health Solutions in Patients with Chronic Diseases in Gastroenterology.

Introduction: Mobile Health (mHealth) applications allow for new possibilities and opportunities in patient care. Their potential throughout the whole patient journey is undisputed. However, the eventual adoption by patients depends on their acceptance of and motivation to use mHealth applications as well as their adherence. Therefore, we investigated the motivation and drivers of acceptance for mHealth and developed an adapted model of the Unified Theory of Acceptance and Use of Technology (UTAUT2). Methods: We evaluated 215 patients with chronic gastroenterological diseases who answered a questionnaire including all model constructs with 7-point Likert scale items. Our model was adapted from the Unified Theory of Acceptance and Use in Technology 2 and includes influencing factors such as facilitating conditions, performance expectancy, hedonic motivation, social influence factors, effort expectancy, as well as personal empowerment and data protection concerns. Model evaluation was performed with structural equation modelling with PLS-SEM. Bootstrapping was performed for hypothesis testing. Results and Conclusion: Patients had a median age of 55.5 years, and the gender ratio was equally distributed. Forty percent received a degree from a university, college, technical academy, or engineering school. The majority of patients suffered from chronic liver disease, but patients with inflammatory bowel diseases, GI cancers, and pancreatic diseases were also included. Patients considered their general technology knowledge as medium to good or very good (78%). Actual usage of mHealth applications in general was rare, while the intention to use them was high. The leading acceptance factor for mHealth applications in our patient group was feasibility, both in terms of technical requirements and the intuitiveness and manageability of the application. Concerns about data privacy did not significantly impact the intention to use mobile devices. Neither the gamification aspect nor social influence factors played a significant role in the intention to use mHealth applications. Interpretation: Most of our patients were willing to spend time on a mHealth application specific to their disease on a regular basis. Acceptance and adherence are ensured by efficient utilization that requires minimum effort and compatible technologies as well as support in case of difficulties. Social influence and hedonic motivation, which were part of UTAUT2, as well as data security concerns, were not significantly influencing our patients' intention to use mHealth applications. A literature review revealed that drivers of acceptance vary considerably among different population and patient groups. Therefore, healthcare and mHealth providers should put effort into understanding their specific target groups' drivers of acceptance. We provided those for a cohort of patients from gastroenterology in this project.

Current Trends and Advancements in the Management of Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) remains a significant global health burden with a high mortality rate. Over the past 40 years, significant progress has been achieved in the prevention and management of HCC. SUMMARY: Hepatitis B vaccination programs, the development of direct acting antiviral drugs for Hepatitis C, and effective surveillance strategies provide a profound basis for the prevention of HCC. Advanced surgery and liver transplantation along with local ablation techniques potentially offer cure for the disease. Also, just recently, the introduction of immunotherapy opened a new chapter in systemic treatment. Finally, the introduction of the BCLC classification system for HCC, clearly defining patient groups and assigning reasonable treatment options, has standardized treatment and become the basis of almost all clinical trials for HCC. With this review, we provide a comprehensive overview of the evolving landscape of HCC management and also touch on current challenges. KEY MESSAGE: A comprehensive and multidisciplinary approach is crucial for effective HCC management. Continued research and clinical trials are imperative to further enhance treatment options and will ultimately reduce the global burden of this devastating disease.

Pituitary metastasis arising from hepatocellular carcinoma: a case report and update of the literature.

Hepatocellular carcinoma (HCC) is the sixth most common neoplasia and the third leading cause of cancer-associated deaths worldwide. Most cases arise in patients with cirrhosis, and early detection through periodic screening can make it potentially curable. The presence of extrahepatic metastases (EHM) affects treatment decisions and curability. The lungs are the most common site for EHM, followed by lymph nodes, bones, and the adrenal glands. Interestingly, approximately only 15 cases of HCC metastasizing to the pituitary gland have been reported so far.The most common symptoms of pituitary metastasis (PM) arising from HCC are nerve palsies affecting the third, fourth, and sixth cranial nerves. Other symptoms, such as diabetes insipidus or pituitary insufficiencies, are present in a minority of cases. Detecting PM is difficult given its rarity. Gold-standard treatments for these patients have not yet been established, but the prognosis is dismal, with a median overall survival of only 4.5 months. In this paper, we present an interesting case of PM as the first symptom of an HCC in a 75-year-old female. We also present an overview of all cases reported to date with emphasis on symptom presentation and survival after diagnosis.Given the improvement of systemic therapy, more cases are diagnosed in both oligometastatic and palliative conditions. Therefore, better approaches and treatment modalities for extrahepatic metastases due to HCC should be defined.

Concomitant Irradiation to Checkpoint Inhibitor Therapy of Hepatocellular Carcinoma Patients: A Systematic Retrospective, Single-Center Analysis.

INTRODUCTION: Immunotherapy has been established as the standard treatment option for patients with advanced hepatocellular carcinoma (aHCC). Despite the increased efficacy, disease progression occurs in a relevant proportion of patients even after an objective response. Combination concepts with locoregional therapy are currently under investigation for hepatic disease but are also in discussion for the control of distant metastasis. Radiotherapy is a highly effective treatment modality for local tumor control. It is also thought to increase the efficacy of checkpoint inhibition and sensitize distant lesions to the effects of immunotherapy, but may potentially increase adverse effects. In our center, few patients with aHCC treated with immune checkpoint inhibitors (ICIs) received concomitant radiotherapy for symptom or disease control. The aim of this study was to retrospectively analyze adverse effects and efficacy of concomitant radiotherapy in patients with aHCC treated with checkpoint inhibition. METHODS: To this aim, patients who received a combination of ICI and radiotherapy in our institution were retrospectively considered for analysis. The predefined inclusion criterion was radiotherapy after initiated checkpoint inhibition and continuation of ICI therapy for at least 8 weeks. Adverse effects and efficacy measurements were performed according to local standards. RESULTS: The database search of 2016-2021 revealed six consecutive patients fulfilling the predefined criteria for concomitant ICI and radiotherapy. Three patients received high-dose-rate brachytherapy (15 Gy) to treat progredient hepatic lesions. Two patients received stereotactic body radiotherapy (SBRT) (25-30 Gy) for symptom control, and 1 patient received brachytherapy and SBRT to treat metastases. No severe adverse events were reported in the period (<6 months) after concomitant radiotherapy. In 5 out of 6 cases, long-term tumor control could be achieved by this therapeutic combination. CONCLUSION: A good efficacy of concomitant radiotherapy and checkpoint inhibition has been achieved with no safety concerns. Further investigations should evaluate the safety, appropriate clinical context, and efficacy of this promising approach.

Changing treatment landscape associated with improved survival in advanced hepatocellular carcinoma: a nationwide, population-based study.

BACKGROUND AND AIMS: The treatment of hepatocellular carcinoma (HCC) is undergoing a historic transformation with the approval of several new systemic therapies in the last few years. This study aimed to examine the impact of this changing landscape on survival and costs in a Western nationwide, real-world cohort. METHODS: A nationwide representative claims database (InGef) was screened for HCC cases between 2015 and 2020. Survival in an era with only sorafenib (period A, January 2015 to July 2018) and after approval of lenvatinib and other systemic treatments (period B, August 2018 to December 2020) was analysed. Health care costs were assessed. RESULTS: We identified 2876 individuals with HCC in the study period. The proportion of patients receiving systemic therapy increased significantly over time, from 11.8% in 2015 to 15.1% in 2020 (p < 0.0001). The median overall survival in period B was 6.5 months (95% confidence interval [CI]: 4.9-8.9) and in period A was 5.3 months (95% CI: 4.5-6.3; p = 0.046). In period B, the median overall survival with lenvatinib was 9.7 months (95% CI: 6.3-18.4) versus 4.8 months with sorafenib (95% CI: 4.0-7.1, p = 0.008). Costs for prescription drugs per patient increased from €6150 in 2015 to €9049 in 2020 (p < 0.0001), and costs for outpatient care per patient increased from €1646 to €2149 (p = 0.0240). CONCLUSION: The approval of new systemic therapies resulted in a survival benefit in patients with HCC. The magnitude of the effect is modest and associated with a moderate increase in health costs.

Clinical Characterization of HCC/CCA Mixed Cancers in a Population-based Cohort.

BACKGROUND AND AIMS: Primary liver cancer (PLC) ranks among of the most common cancers worldwide. Within this group, a minority of cases displays characteristics of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), known as combined hepatocellular cholangiocarcinoma (cHCC- CCA). Currently, there is no specific standardized therapy for these mixed tumors. Therefore, the aim of our study was to analyze the clinical course, treatment and outcome of cHCC-CCA patients in a European population-based registry. METHODS: We investigated 9,144 patients with PLC (6,622 HCC, 2,356 iCCA, and 166 cHCC-CCA) diagnosed between 2009 and 2020. All data were obtained from Clinical Cancer Registry of Baden-Württemberg (BW), Germany. RESULTS: In all three groups patients were predominantly male (82%, 57%, and 68% for HCC, iCCA and cHCC-CCA groups, respectively). 48% of cHCC-CCA patients were diagnosed as stage IV cancers, which was more than for HCC (31%) but less compared to CCA (64%). Overall median survival of cHCC-CCA patients was worse compared to HCC (9-13 months vs. 15.5 months, p<0.001) and rather comparable to CCA (11.8 months). CONCLUSIONS: Our data demonstrated that cHCC-CCA tumors appear to have a distinct clinical course with worse overall survival compared to HCC. Thus, identification of these cancers by histopathology is essential in order to further characterize this tumor entity and to provide accurate treatment to these patients.

Efficacy of Co-Medications in Patients with Alcoholic Liver Disease.

BACKGROUND: Alcoholic liver disease (ALD) is still increasing and leads to acute liver injury but also liver cirrhosis and subsequent complications such as liver failure or hepatocellular carcinoma (HCC). As most patients fail to achieve alcohol abstinence, it is essential to identify alternative treatment options in order to improve the outcome of ALD patients. METHODS: Evaluating two large cohorts of patients with ALD from the USA and Korea with a total of 12,006 patients, we investigated the effect on survival of aspirin, metformin, metoprolol, dopamine, and dobutamine drugs in patients with ALD between 2000 and 2020. Patient data were obtained through the "The Observational Health Data Sciences and Informatics consortium," an open-source, multi-stakeholder, and interdisciplinary collaborative effort. RESULTS: The use of aspirin (p = 0.000, p = 0.000), metoprolol (p = 0.002, p = 0.000), and metformin (p = 0.000, p = 0.000) confers a survival benefit for both AUSOM- and NY-treated cohorts. Need of catecholamines dobutamine (p = 0.000, p = 0.000) and dopamine (p = 0.000, p = 0.000) was strongly indicative of poor survival. ß-Blocker treatment with metoprolol (p = 0.128, p = 0.196) or carvedilol (p = 0.520, p = 0.679) was not shown to be protective in any of the female subgroups. CONCLUSION: Overall, our data fill a large gap in long-term, real-world data on patients with ALD, confirming an impact of metformin, acetylsalicylic acid, and ß-blockers on ALD patient's survival. However, gender and ethnic background lead to diverse efficacy in those patients.

Distance Matters: Correlation of Hepatocellular Carcinoma Nodule Distance to Overall Survival.

INTRODUCTION: Hepatocellular carcinoma (HCC) may occur with several simultaneous tumor foci in the liver (multifocal HCC). Molecular biology indicated that the larger the distance between two tumor nodules, the more those two nodules differed in their genetic composition. Therefore, we explored whether the overall survival (OS) of patients with HCC depends on the mutual distance of the HCC nodules. METHODS: In a retrospective study of 92 patients, CT/MRI images and survival data of the patients were collected. Based on the CT or MRI images at the time of diagnosis, the size of each tumor, the distance between the centers (center distance), and adjacent edges (edge distance) of the tumor nodules were measured, respectively. These data, combined with the number of tumor nodules and clinical characteristics, were compared with the patient's OS data. RESULTS: As expected, the average tumor diameter was significantly associated with patient survival in univariate Cox regression analysis (p = 0.00028, hazard ratio [HR] = 1.2). However, in multivariate analysis, the average center distance (p = 0.036, HR = 1.18) and average edge distance (p = 0.033, HR = 0.84) were also significantly associated with survival. CONCLUSION: Thus, not only the size of multiple HCC lesions but also their distance is important for the prognosis of patients with HCC. This may be of particular interest in patients with two nodules and BCLC B and C stages for the selection of therapeutic modalities and/or procedures.

Efficacy and safety of immune checkpoint inhibitor rechallenge in individuals with hepatocellular carcinoma.

Background & Aims: We investigated the efficacy and safety of immune checkpoint inhibitor (ICI) rechallenge in patients with hepatocellular carcinoma (HCC) who received ICI-based therapies in a previous systemic line. Methods: In this international, retrospective multicenter study, patients with HCC who received at least two lines of ICI-based therapies (ICI-1, ICI-2) at 14 institutions were eligible. The main outcomes included best overall response and treatment-related adverse events. Results: Of 994 ICI-treated patients screened, a total of 58 patients (male, n = 41; 71%) with a mean age of 65.0±9.0 years were included. Median systemic treatment lines of ICI-1 and ICI-2 were 1 (range, 1-4) and 3 (range, 2-9), respectively. ICI-based therapies used at ICI-1 and ICI-2 included ICI alone (ICI-1, n = 26, 45%; ICI-2, n = 4, 7%), dual ICI regimens (n = 1, 2%; n = 12, 21%), or ICI combined with targeted therapies/anti-VEGF (n = 31, 53%; n = 42, 72%). Most patients discontinued ICI-1 due to progression (n = 52, 90%). Objective response rate was 22% at ICI-1 and 26% at ICI-2. Responses at ICI-2 were also seen in patients who had progressive disease as best overall response at ICI-1 (n = 11/21; 52%). Median time-to-progression at ICI-1 and ICI-2 was 5.4 (95% CI 3.0-7.7) months and 5.2 (95% CI 3.3-7.0) months, respectively. Treatment-related adverse events of grade 3-4 at ICI-1 and ICI-2 were observed in 9 (16%) and 10 (17%) patients, respectively. Conclusions: ICI rechallenge was safe and resulted in a treatment benefit in a meaningful proportion of patients with HCC. These data provide a rationale for investigating ICI-based regimens in patients who progressed on first-line immunotherapy in prospective trials. Impact and implications: Therapeutic sequencing after first-line immune checkpoint inhibitor (ICI)-based therapy for advanced hepatocellular carcinoma (HCC) remains a challenge as no available second-line treatment options have been studied in immunotherapy-pretreated patients. Particularly, the role of ICI rechallenge in patients with HCC is unclear, as data from prospective trials are lacking. We investigated the efficacy and safety of ICI-based regimens in patients with HCC pretreated with immunotherapy in a retrospective, international, multicenter study. Our data provide the rationale for prospective trials investigating the role of ICI-based regimens in patients who have progressed on first-line immunotherapy.

Value of contrast-enhanced ultrasound for vascular diseases of the liver - current indications and open questions.

Contrast-enhanced ultrasonography (CEUS) is a widely available and well-tolerated technique that can expand the diagnosis of a variety of vascular liver diseases. This paper presents an overview of the current possibilities of the use of CEUS in vascular liver diseases. Particularly where Doppler sonography has technical limitations, CEUS provides additional opportunities to visualize vascular thrombosis and other obstructions restricting blood flow. When CT or MRI contrast agents cannot be used because of severe allergy or renal insufficiency, CEUS can be a valuable diagnostic alternative and has demonstrated comparable diagnostic performance in at least some vascular liver diseases, such as portal vein thrombosis. In addition, CEUS works without radiation and, therefore, might be particularly suitable for young patients and children. This may be useful, for example, in congenital disorders such as persistent umbilical vein or preduodenal portal vein. Vascular liver disease is rare and comprehensive data are still lacking, but the available literature provides promising insights into potential new ways to study vascular liver disease. Although most studies are based on small sample sizes or even case reports, the high diagnostic utility is undisputed.

Characteristics and outcome of patients with small bowel adenocarcinoma (SBA).

BACKGROUND: Small bowel adenocarcinoma (SBA) remains a rare malignancy accounting for less than 5% of all the gastrointestinal tract cancers. However, only limited data and expert guidelines are available for this entity. As a result, treatment concepts are predominantly derived from colorectal cancer. METHODS: To substantiate data on the course of disease, diagnosis and treatment of SBA, we performed a population-based analysis from a Bavarian population of 2.2 million people. RESULTS: We identified 223 patients with SBA. Mean age at diagnosis was 67.8 years and patients were diagnosed rather late (34.5% UICC stage IV). Largest proportion of these patients were diagnosed with adenocarcinoma of the duodenum (132 patients, 59.2%) and most patients were diagnosed with late stage cancer, stage IV (70 patients, 31.4%). With respect to treatment, most patients underwent primary surgery (187 patients, 84.6%). Systemic therapy seemed to have an impact in UICC stage IV patients but not in UICC stage IIB or III. The 5-year survival rate was 29.0%. This was significantly less compared to colon cancer in the same cohort, which was 50.0%. Furthermore, median survival of patients with small bowel cancer was only 2.0 years (95% CI 1.4-2.5) compared to 4.9 years (95% CI 4.8-5.1) of patients with colon cancer. CONCLUSION: SBA showed a distinct epidemiology compared to colon cancer. Thus, data acquisition particularly on systemic treatment are paramount, with the objective to complement the available guidelines.

Management of Hepatic Sarcoidosis.

BACKGROUND AND AIMS: Liver involvement in sarcoidosis may occur in up to 60% of all patients. As many patients experience only minor symptoms, a high number of undiagnosed cases must be assumed. In order to successfully identify patients with hepatic sarcoidosis, a throughout characterization of these patients and their course of disease is necessary. METHODS: We collected 40 patients from four German centers to evaluate current treatment standards and course of disease. All of our patients underwent liver biopsy with histologically proven granulomatous hepatitis. RESULTS: Detailed characterization of our patients showed an overall benign course of disease. Treatment was very diverse with glucocorticoids for 1 year in 55% (22/40), 5-10 years in 18% (7/40), and permanently in 18% (7/40). Other treatments included disease-modifying anti-rheumatic drugs (DMARDs), the conventional non-biological type in 53% of all patients (of these 81% received azathioprine, 46% metotrexate, 10% hydroxychloroquine, 10% mycophenolate mofetil and 10% cyclophosphamide and biologicals in 8%. Despite these very diverse treatments, patients generally showed slow progression of the disease. Two patients died. None of our patients received a liver transplantation. CONCLUSIONS: Patients received diverse treatments and generally showed slow progression of the disease. Based on our experience, we proposed a diagnostic work up and surveillance strategy as a basis for future, prospective register studies.

Deep View of HCC Gene Expression Signatures and Their Comparison with Other Cancers.

BACKGROUND: Gene expression signatures correlate genetic alterations with specific clinical features, providing the potential for clinical usage. A plethora of HCC-dependent gene signatures have been developed in the last two decades. However, none of them has made its way into clinical practice. Thus, we investigated the specificity of public gene signatures to HCC by establishing a comparative transcriptomic analysis, as this may be essential for clinical applications. METHODS: We collected 10 public HCC gene signatures and evaluated them by utilizing four different (commercial and non-commercial) gene expression profile comparison tools: Oncomine Premium, SigCom LINCS, ProfileChaser (modified version), and GENEVA, which can assign similar pre-analyzed profiles of patients with tumors or cancer cell lines to our gene signatures of interests. Among the query results of each tool, different cancer entities were screened. In addition, seven breast and colorectal cancer gene signatures were included in order to further challenge tumor specificity of gene expression signatures. RESULTS: Although the specificity of the evaluated HCC gene signatures varied considerably, none of the gene signatures showed strict specificity to HCC. All gene signatures exhibited potential significant specificity to other cancers, particularly for colorectal and breast cancer. Since signature specificity proved challenging, we furthermore investigated common core genes and overlapping enriched pathways among all gene signatures, which, however, showed no or only very little overlap, respectively. CONCLUSION: Our study demonstrates that specificity, independent validation, and clinical use of HCC genetic signatures solely relying on gene expression remains challenging. Furthermore, our work made clear that standards in signature generation and statistical methods but potentially also in tissue preparation are urgently needed.

Second Cancer After Additive Chemotherapy in Patients With Colon Cancer.

BACKGROUND: Additive chemotherapeutic treatment of UICC-stage -III / IV colon cancer with fluorouracil, leucovorin and oxaliplatin is widely accepted as current standard of treatment after R0-resection. However, as patients.. survival is increasing, long-term side effects of chemotherapeutic agents such as second cancer development are becoming increasingly important. PATIENTS: We therefore investigated a total of 2 856 Patients with UICC-stage III / IV colon cancer, 223 of whom (7.8%) had developed a subsequent second cancer. RESULTS: Median follow-up was 73.2 months (range 209.9 months, 95%-CI 69.8-76.9). Most frequent second cancers were prostate cancer (18.4%), colon cancer (16.1%), breast cancers (8.1%), lung cancer (8.1%), rectal cancer (4.9%) and uterine cancer (4.9%). However, in comparison to non-treated patients this did not represent a significantly increased risk for subsequent second cancer in patients after treatment with additive chemotherapy. Of interest, our data suggest a significantly decreased second cancer rate in patients treated with FOLFOX compared to FUFOL for additive treatment. CONCLUSIONS: Second cancer development was not increased after additive chemotherapy for colon cancer, which is a novel aspect in the ongoing discussions on reduction of adjuvant treatment to 3 months or treatment of lymph node negative patients. Novelty and Impact Statement To our knowledge, this is the first population-based study analyzing second cancer development after additive chemotherapy in patients with UICC III-IV colon cancer. The results have an important impact on the surveillance and long-term follow-up of cancer patients.

Comparative Response of HCC Cells to TKIs: Modified in vitro Testing and Descriptive Expression Analysis.

Introduction: Although the treatment paradigm for hepatocellular carcinoma (HCC) has recently shifted in favour of checkpoint inhibitor (CPI)-based treatment options, the tyrosine kinase inhibitors (TKI) currently approved for the treatment of HCC are expected to remain the cornerstone of HCC treatment alone or in combination with CPIs. Despite considerable research efforts, no biomarker capable of predicting the response to specific TKIs has been validated. Thus, personalized approaches to HCC may aid in determining optimal treatment lines for 2nd and 3rd lines. To identify new biomarkers, we examined differential sensitivity and investigated potential transcriptomic predictors. Methods: To this aim, the sensitivity of nine HCC cell lines to sorafenib, lenvatinib, regorafenib, and cabozantinib was evaluated by a prolonged treatment scheme to determine their respective growth rate inhibition concentrations (GR50). Subgroups discriminated by GR50 values underwent differential expression and gene set enrichment analysis (GSEA). Results: The nine cell lines showed broadly different sensitivities to different TKIs. GR50 values of sorafenib and regorafenib clustered closer in all cell lines, whereas treatments with lenvatinib and cabozantinib showed diversified GR50 values. GSEA showed the activation of specific pathways in sensitive vs non-sensitive cell lines. A signature consisting of 14 biomarkers (GAGE12H, GJB6, PTCHD3, PRH1-PRR4, C6orf222, HBB, C17orf99, GOLGA6A, CRYAA, CCL23, RP11-347C12.3, RP11-514O12.4, FAM180B, and TMPRSS4) discriminates the cell lines' response into three distinct treatment profiles: 1) equally sensible to sorafenib, regorafenib and cabozantinib, 2) sensible to lenvatinib, and 3) more sensible to regorafenib than sorafenib. Conclusion: We observed diverse responses to either of the four TKIs. Subgroup analysis of TKI effectiveness showed distinct transcriptomic profiles and signaling pathways associated with responsiveness. This prompts more extensive studies to explore and validate pharmacogenomic and transcriptomic strategies for a personalized treatment approach, particularly after the failure of CPI treatment.

Clinical effects and safety of different transarterial chemoembolization methods for bridging and palliative treatments in hepatocellular carcinoma.

PURPOSE: We assessed and compared clinical effects and safety endpoints of three methods of transarterial chemoembolization (TACE), conventional (cTACE), with drug-eluting beads (DEB-TACE), and with degradable starch microspheres (DSM-TACE), used in patients with hepatocellular carcinoma (HCC) in the bridging to liver transplant (LT) and the palliative setting. METHODS: In our center, 148 patients with HCC underwent 492 completed TACE procedures between 2008 and 2017 (158 for bridging to LT; 334 for palliative treatment) which we analyzed retrospectively. Of these procedures, 348 were DEB-TACE, 60 cTACE, and 84 DSM-TACE. RESULTS: The cTACE procedure revealed a significantly longer period of hospitalization (p = 0.02), increased occurrence of nausea (p = 0.025), and rise in alanine transaminase (ALT) levels (p = 0.001), especially in the palliative setting. In the bridging to LT cohort, these clinical endpoints did not reach statistical significance. CONCLUSIONS: The clinical safety of different TACE methods for HCC in both the palliative and the bridging to LT setting was equivalent. In the palliative setting, the cTACE procedure revealed an increased risk for adverse clinical effects such as nausea, elevation of ALT, and a prolonged period of hospitalization what might either be related to the systemic effects of the chemotherapeutic agent or to the differences in both collectives. Thus, further studies must be conducted on a larger number of TACE procedures to effectively explore the clinical side effects of the various TACE variants.

Conventional ultrasound for diagnosis of hepatic steatosis is better than believed.

BACKGROUND: Hepatic steatosis is a condition frequently encountered in clinical practice, with potential progression towards fibrosis, cirrhosis, and hepatocellular carcinoma. Detection and staging of hepatic steatosis are of most importance in nonalcoholic fatty liver disease (NAFLD), a disease with a high prevalence of more than 1 billion individuals affected. Ultrasound (US) is one of the most used noninvasive imaging techniques used in the diagnosis of hepatic steatosis. Detection of hepatic steatosis with US relies on several conventional US parameters, which will be described. US is the first-choice imaging in adults at risk for hepatic steatosis. The use of some scoring systems may add additional accuracy especially in assessing the severity of hepatic steatosis. SUMMARY: In the presented paper, we discuss screening and risk stratification, ultrasound features for diagnosing hepatic steatosis, B-mode criteria, focal fatty patterns and Doppler features of the hepatic vessels, and the value of the different US signs for the diagnosis of liver steatosis including classifying the severity of steatosis using different US scores. Limitations of conventional B-mode and Doppler features in the evaluation of hepatic steatosis are also discussed, including those in grading and assessing the complications of steatosis, namely fibrosis and nonalcoholic steatohepatitis. KEY MESSAGES: Ultrasound is the first-line imaging examination for the screening and follow-up of patients with liver steatosis. The use of some scoring systems may add additional accuracy in assessing the severity of steatosis. Conventional B-mode and Doppler ultrasound have limitations in grading and assessing the complications of steatosis.

RASSF1A independence and early galectin-1 upregulation in PIK3CA-induced hepatocarcinogenesis: new therapeutic venues.

Aberrant activation of the phosphoinositide 3-kinase (PI3K)/AKT/mTOR and Ras/mitogen-activated protein kinase (MAPK) pathways is a hallmark of hepatocarcinogenesis. In a subset of hepatocellular carcinomas (HCCs), PI3K/AKT/mTOR signaling dysregulation depends on phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations, while RAS/MAPK activation is partly attributed to promoter methylation of the tumor suppressor Ras association domain-containing protein 1 (RASSF1A). To evaluate a possible cocarcinogenic effect of PIK3CA activation and RASSF1A knockout, plasmids expressing oncogenic forms of PIK3CA (E545K or H1047R mutants) were delivered to the liver of RASSF1A knockout and wild-type mice by hydrodynamic tail vein injection combined with sleeping beauty-mediated somatic integration. Transfection of either PIK3CA E545K or H1047R mutants sufficed to induce HCCs in mice irrespective of RASSF1A mutational background. The related tumors displayed a lipogenic phenotype with upregulation of fatty acid synthase and stearoyl-CoA desaturase-1 (SCD1). Galectin-1, which was commonly upregulated in preneoplastic lesions and tumors, emerged as a regulator of SCD1. Co-inhibitory treatment with PIK3CA inhibitors and the galectin-1 inhibitor OTX008 resulted in synergistic cytotoxicity in human HCC cell lines, suggesting novel therapeutic venues.