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Öğe Altruism in Relation to Live Donor Liver Transplants for Liver Cancer(Springer International Publishing, 2022) Carr B.I.; Baskiran A.Altruism in regard to liver transplantation is the desire to donate part of the liver and thus increase the life and welfare of the individual who needs the organ, without any expectation of reward or gain by the donor. It is regarded as a basic principle of all types of transplantation. Live organ liver donation is an illustration of altruism and is important in many places where medical need outstrips available cadaveric liver donation. The near universality of altruism propels many prospective donors to try and save or extending the lives of persons suffering from liver disease. However, both altruistic donors and the transplant patients need psycho-social support, often on an ongoing basis. The examples of some donor conversations illustrate the complexity, fears and dynamics at play in so many families. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.Öğe Biological aspects of HCC(Springer International Publishing, 2021) Carr B.I.Much has been published on experimental chemical hepatocarcinogenesis, but much less on experimental viral hepatocarcinogenesis. Furthermore, animal models for clinical HCC are typically missing one important component or other of the human disease, such as PVT. Despite this, much is understood about hepatocarcinogenic mechanisms and the biological principles underlying many clinical phenotypic HCC features. These include recent understanding of the importance of tumor microenvironment and the inflammatory context, immune signaling within the liver, cell growth and signaling pathways, resistance to cytotoxic chemotherapy as an inherent HCC property, the significance of vitamin K through understanding of the HCC biomarker, DCP, and the increasing importance of circulating tumor cells and DNA as a "liquid" minimally invasive biopsy. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2021. All rights reserved.Öğe Bringing It All Together(Springer International Publishing, 2022) Carr B.I.The idea that the mind responds to processes in the body and conversely, that the bodily functions can be influenced by the mind, is referred to as mind–body relationship. Recent studies in the diverse areas of metabolic, immune, endocrine, and gene expression effects from stress and depression have begun to permit a systems view of the effects of the emotions of cancer patients on specific cellular processes that could modulate cancer cell growth, positively or negatively. These concepts form a rational basis for considering the use of psychological therapy-cognitive, antidepressant, or relaxant not only for symptom management but possibly as part of total cancer patient management. We do not yet know that mind affects cancer biology and thus prognosis, but there are both clinical trials data and cancer patient biochemical data that point to that possibility. All patients live as part of a social and family context, with a two-way interaction between the perception of the mind of a body disease and the reaction of the mind to its significance, involving fear, hopefulness, spirituality, caring, and coping. These reactions are, in turn, capable of producing both destructive and helpful bodily effects. Many of these aspects of cancer patient and caregiver concerns and their management are addressed in this chapter. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.Öğe Comparison of patients with hepatitis B virus-associated hepatocellular carcinoma: Data from two hospitals from Turkey and China(John Wiley and Sons Inc, 2023) Carr B.I.; Rui F.; Ince V.; Yilmaz S.; Zhao X.; Feng Y.; Li J.Aims: There are many studies on the incidence of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC), but very little is known about the HCC features in different populations. The study aimed to compare characteristics in two cohorts of patients with HBV-associated hepatocellular carcinoma from Turkey and China. Methods: Data on patients with HBV-associated HCC diagnosed by imaging or liver biopsy were retrospectively collected from Shandong Provincial Hospital (n = 578) and Inonu University Hospital (n = 359) between January 2002 and December 2020, and the liver function and HCC characteristics were compared. Continuous variables were compared using Student's t-test or Mann–Whitney U test and categorical variables were compared using the ?² test or Fisher's exact test. Results: The patients in the Turkish cohort had significantly worse Child-Pugh scores (Child-Pugh A: 38.3% vs. 87.9%; Child-Pugh B: 40.3% vs. 11.1%; Child-Pugh C: 21.4% vs. 1.0%; p < 0.001) and significantly higher levels of aspartate aminotransferase (66.5 [38.0?126.0] vs. 36.0 [27.0?50.0] IU/L; p < 0.001), alanine aminotransferase (47.5 [30.0?87.3] vs. 33.0 [24.0?45.0] IU/L; p < 0.001), total bilirubin (20.8 [13.7?39.3] vs. 17.9 [13.8?24.0] mg/dL; p < 0.001), and lower albumin levels (32.0 [26.0?39.0] vs. 40.0 [36.1?43.8] g/L; p < 0.001) than patients in Chinese cohort. The tumor characteristics showed the Barcelona Clinic Liver Cancer (BCLC) score (BCLC 1: 5.1% vs. 71.8%; BCLC 2: 48.7% vs. 24.4%; BCLC 3: 24.4% vs. 3.8%; BCLC 4: 21.8% vs. 0; all p < 0.001), maximum tumor diameter (5.0 [3.0?9.0] vs. 3.5 [2.5?6.0] cm; p < 0.001), alpha-fetoprotein values (27.7 vs. 13.2 ng/mL; p < 0.001), and percentage of patients with portal vein tumor thrombus (33% vs. 6.1%; p < 0.001) were all significantly worse in the Turkish cohort compared with Chinese cohort. Conclusions: HBV-associated HCC from the Turkish cohort had worse liver function and more aggressive clinical characteristics than patients from the Chinese cohort. © 2023 The Authors. Portal Hypertension & Cirrhosis published by John Wiley & Sons Ltd on behalf of Chinese Medical Association.Öğe Future directions(Springer International Publishing, 2021) Carr B.I.Several trends and current needs can be identified. HCC tumor registries everywhere need to be a high priority, in order to estimate the size of the problem and the needs. Universal neonatal HBV vaccination needs to be instituted, for a major preventable cause. Obesity is a current public health problem and needs to be addressed through public education. Since survival results are best when HCC is diagnosed at early stages, where results of treatment are best. Similarly, biobanks of blood and surgically removed tumor tissue of current patients are an investment in future research in prognostic biomarkers. Private and public sanitation needs to be emphasized in the effort to block horizontal transmission of hepatitis virus. The Middle East comprises a huge population with large numbers of HCC patients, representing a large commercial market. Clinical trials are needed on the safety and effectiveness of new agents in this population. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2021. All rights reserved.Öğe Öğe Individual patient assessment and therapy decision-making in a live donor-based liver transplant institute(Springer International Publishing, 2021) Carr B.I.; Yilmaz S.; Isik B.; Kutlu R.Patients with HCC present with both their tumor and underlying liver disease, requiring input from several disciplines for optimal therapeutic decision-making. We describe our method, which emphasizes the importance of a multidisciplinary approach and a tumor board. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2021. All rights reserved.Öğe Inflammation, Chronic Disease, and Cancer: Is Psychological Distress the Common Thread?(Springer International Publishing, 2022) Carr F.N.; Sosa E.M.; Carr B.I.Mounting evidence suggests that the inflammatory mechanism plays a central role in the development and exacerbation of multiple chronic illnesses, including gastrointestinal, pulmonary, and cardiovascular disease, as well as obesity and rheumatoid arthritis. It has further been suggested that chronic inflammation is correlated with various types of cancer. While multiple studies have demonstrated that certain chronic diseases predict increased risk of malignancies, recent scholarship suggests that inflammatory mechanisms likely serve as a major factor in the pathogenesis of many cancer types. As psychological stress is known to influence individual levels of pro-inflammatory cytokines, it is possible that chronic stress and depression may indirectly contribute to cancer development. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.Öğe Liver Cancer in the Middle East(Springer International Publishing, 2021) Carr B.I.This book aims to illuminate the causes, incidence, and treatments of Hepatocellular Carcinoma(HCC) or liver cancer in the politically important and societally diverse region of the Middle East. Taking a flexible and inclusive view, it examines the influences of geography, crops and diet, ethnicity, and local behavior on both diagnosis and outcomes of this disease. Understanding the different causes of liver cancer enables effective strategies for both prevention and early diagnosis while knowledge of the different treatment modalities, their uses and limitations, availability and costs, works to inform rational treatment provision and selection. Divided into four sections, this book considers the causes and clinical syndromes associated with HCC, provides a detailed overview of clinical HCC and treatment modalities, describes country-specific clinical HCC experience and practice, and considers future needs and the potential for HCC collaborations across the region. Liver Cancer in the Middle East is a useful resource for clinicians seeking insight into the second highest cause of death from cancer worldwide, governments planning social and medical services for their peoples, as well as for international aid agencies prioritizing donations. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2021. All rights reserved.Öğe The need for region-wide HCC collaborations(Springer International Publishing, 2021) Carr B.I.Ten areas of collaboration for improving our subject are suggested. They include (1) a common HCC database; (2) HCC database with geographic patient locations, to detect HCC hotspots; (3) a Middle East HCC biobank; (4) public health teaching and awareness to limit horizontal hepatitis transmission; (5) conferences for mutual education and to foster collaborations; (6) transnational clinical trials; (7) biosimilar fabrication to make new effective agents more affordable; (8) identifying barriers to early diagnosis; (9) quality of life awareness and assessment; and (10) identification of unmet needs in HCC management, including downstaging therapies, post-resection adjuvant therapy, HBV therapy to decrease HCC aggressiveness, biomarkers for low-AFP patients, and adoption of circulating tumor cell/fragment assays for liquid biopsy and radiotherapies for PVT treatment. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2021. All rights reserved.Öğe Overview of clinical HCC and its management(Springer International Publishing, 2021) Carr B.I.HCC is an important cancer worldwide with over 800,000 new annual cases globally but has huge geographic differences in incidence. It is predominantly a cancer of the less developed world, where its burden is heaviest. Its main causes are known and in large part preventable: HBV, HCV, alcoholism, and obesity. Just as widespread neonatal immunization is having a large preventive effect in those regions where it has become policy, a recently appreciated cause is increasing, namely, obesity-associated cirrhosis. As with other solid tumors, best survival rates are achieved when early diagnosis permits aggressive therapy. This in turn highlights the importance of surveillance. Advances in survival have been made in the small subset of patients with limited tumor burden who are eligible for liver transplantation. However, most patients present at too advanced a stage for this. Nevertheless, in the last 3 years, major increases in response rates and survival have been found from new clinical trials that involve immune checkpoint inhibitor agents. Whether these expensive drugs can be made available to the large proportion of patients in less economically advanced countries will be a next challenge. As always in medicine, prevention and early detection are the bedrock for extending survival in HCC patients and potential patients. Given the complexities involved in therapeutic decision-making for each patient who has two diseases - cancer and cirrhosis - a multidisciplinary team is widely regarded as optimal. Wonderful but expensive new HCC therapies are available, but typically for a minority of the patients. Nevertheless, in HCC patients with chronic HBV, nucleoside analog HBV treatments also seem to improve survival and reduce HCC recurrences in resected patients. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2021. All rights reserved.Öğe Psychological Aspects of Cancer: A Guide to Emotional and Psychological Consequences of Cancer, Their Causes, and Their Management, Second Edition(Springer International Publishing, 2022) Steel J.L.; Carr B.I.This book addresses the unmet needs of the medical community in dealing with the psychological problems, particularly anxiety and depression, of patients diagnosed with cancer. Providing a scholarly review of the impact of cancer diagnosis on patients’ emotional and psychological status, as well as the evidence that psychological factors impact cancer occurrence and biological behavior, this book explores the therapeutic implications of such converse dynamics. Chapters review financial toxicity, eHealth, palliative care, mindfulness, sleep and cancer, social support and cancer, cultural diversity, pediatric and adolescent oncology, and geriatric oncology. While intended primarily for the professional readership of oncologists, psychologists, psychiatrists, social workers, and palliative care physicians, a final chapter also provides practical information on available resources for patients. This fully updated and expanded new edition of Psychological Aspects of Cancer: A Guide to Emotional and Psychological Consequences of Cancer, Their Causes, and Their Management provides practitioners with cutting edge knowledge as well as practical information that translates into better care for patients with cancer. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.Öğe Ramucirumab and GSK1838705A enhance the inhibitory effects of low concentration sorafenib and regorafenib combination on HCC cell growth and motility(MDPI AG, 2019) D’Alessandro R.; Refolo M.G.; Iacovazzi P.A.; Pesole P.L.; Messa C.; Carr B.I.Several new multikinase inhibitors have recently been introduced into clinical practice for hepatocellular carcinoma (HCC) therapy. Small increases in survival were reported as well as considerable toxicity. There is thus a need for effective therapies with lower toxicities. We examined whether a combination of sorafenib and regorafenib might also be effective at very low concentrations, with resulting potential for lessened clinical toxicity. MTT test, clonogenic assay, Ki67 staining and cell cycle analysis were assessed for cell proliferation and Annexin V and western blotting analysis relative to the expression of cleaved Caspase-3 and BID for cell apoptosis. In these experimental conditions cell growth and migration were potently inhibited and apoptosis induced even in HCC cells producing high alpha fetoprotein (AFP) levels (clinically worse prognosis). The combination also inhibited levels of the two HCC biomarkers, AFP and des gamma carboxy prothrombin (DCP). Additional inhibition of Vascular Endothelial Growth Factor Receptor (VEGFR) or Insulin-like Growth Factor 1 Receptor (IGF1R) enhanced effects on AFP and DCP levels, cell growth inhibition and MAPK and PI3K/Akt signaling inhibition due to sorafenib/regorafenib combination. These combinations have the potential for decreased toxicity while simultaneously enhancing therapeutic effects. This potential decrease in toxicity is being explored in ongoing studies. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.Öğe Review of therapies for intermediate and advanced stage hepatocellular carcinoma, not suitable for curative therapies: a rapidly changing landscape(OAE Publishing Inc., 2019) Carr B.I.Recent clinical trials and new agents have permitted greater clarity in the choice of effective agents for that majority of patients with hepatocellular carcinoma who have advanced disease at diagnosis and thus cannot be offered potentially curative resection, ablation or liver transplantation. The main treatment for these patients remains chemoembolization, although evidence for selective internal radiation therapy (SIRT) with SIR-Spheres or Theraphere, is beginning to suggest that the results with this may be comparable with less toxicity. Patients who have failed chemoembolization or SIRT or have metastatic disease at presentation are suitable for the multikinase inhibitor sorafenib (nexavar) or newly-approved lenvatinib (lenvima) as first line therapies. The choice between which of them to use first is not currently clear. Patients who have failed sorafenib can be offered a choice of FDA-approved regorafenib (stivarga) or immune checkpoint inhibitor nivolumab (opdivo) as second line agents. For that considerable percent of patients presenting with macroscopic portal vein thrombosis, the choice appears to be between multikinase inhibitor or SIRT, given the potential toxicity of chemoembolization in this setting. However, considering the potency of both nivolumab and regorafenib and the pipeline of new agents such as atezolizumab (tecentriq) in current clinical trials, including new immune checkpoint inhibitors, this landscape may change within a couple of years, especially if new evidence arises for the superior effectiveness of combinations of any of these agents over single agents. © The Author(s) 2019.
