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Öğe Can the Limits of Liver Transplantation Be Expanded in Perihilar Cholangiocarcinoma?(Springer, 2022) Yilmaz, Sezai; Carr, Brian, I; Akbulut, SamiThe most common location of cholangiocarcinomas is the perihilar region with a frequency of 50-70%. Current standard treatment for perihilar cholangiocarcinomas (pCCA) is surgical resection. In cases where resection treatment is possible, the 5-year survival rate is 8-40%. However, using a very strict patient selection, neoadjuvant radiochemotherapy (NRCT), staging laparotomy, and liver transplantation (LT), called the Mayo protocol, 5-year survivals of up to 70% in pCCA were reported. This treatment protocol clearly requires an intensive workforce and a harmonious multidisciplinary approach. Reoperation and retransplantation rates are high, which is a reflection of the NRCT. Multicenter studies, systemic reviews, and meta-analysis results, comparing both resection and LT in pCCA treatment and evaluating only LT results, pointed to LT with strict patient selection and full compliance with the treatment. The results of centers experienced in LT are better in treating pCCA. According to Mayo clinical data, histopathological diagnosis could not be obtained in half of the patients with pCCA before NRCT was given. This situation can be explained by the necrosis of the tumor due to the effect of NRCT and the fact that the tumor cannot be detected in the explant liver. This situation raises the following questions: did all patients actually have pCCA? Were these good results due to some patients not having pCCA? The 5-year survival rate was worse in patients with a pathological diagnosis than those without a pathological diagnosis. However, interestingly, recurrence rates were statistically similar in both groups. There was no difference in survival between LT and resection in the R0N0 subgroup in de novo pCCA. There are still many issues that need to be addressed and corrected in pCCA, which is one of the most problematic indications for LT. Significant success has been achieved with NRCT, staging laparotomy, and LT in selected patients with pCCA developing on the basis of PSC or early-stage unresectable de novo pCCA. It can be expected that new NRCT modalities will provide better survival by expanding the indications for LT in pCCA.Öğe A Combination of Blood Lymphocytes and AST Levels Distinguishes Patients with Small Hepatocellular Carcinomas from Non-cancer Patients(Springer, 2021) Carr, Brian, I; Bag, Harika Gozukara; Ince, Volkan; Akbulut, Sami; Ersan, Veysel; Usta, Sertac; Isik, BurakPurpose HCC patients typically present at an advanced tumor stage, in which surgical therapies cannot be used. Screening ultrasound exams can increase the numbers of patients diagnosed with small tumors, but are often not used in patients at risk for HCC. We evaluated clinically available and cheap potential blood tests as biomarkers for screening patients at risk for HCC. Methods A comparison was made of commonly used blood count and liver function parameters in a group of patients (n = 101) with small HCCs (<= 3 cm) or without HCC (n = 275), who presented for liver transplantation in our institute. Results Significant differences were found for blood lymphocytes and AST levels. This 2-parameter combination was found to be significantly different between patients with small HCCs versus no HCC. Using the combination of lymphocytes and AST levels to dichotomize the HCC patients, only blood levels of alpha-fetoprotein among the tumor characteristics were found to be significantly different among the 2 HCC groups, as well as levels of blood total bilirubin, ALKP, and PLR ratio. The results were confirmed using a separate smaller cohort of non-transplanted small size HCC patients. Conclusion The combination of elevated blood levels of lymphocyte counts and AST levels holds promise for screening of patients with chronic liver disease who are at risk for HCC.Öğe Critical overview of resection for Bismuth-Corlette type IV perihilar cholangiocarcinoma(Taylor & Francis Ltd, 2023) Ersan, Veysel; Usta, Sertac; Aydin, Cemalettin; Carr, Brian, I; Karatoprak, Sinan; Yilmaz, SezaiBackground Current standard treatment for perihilar cholangiocarcinoma (pCCA) is surgical resection. Bismuth-Corlette (BC) type IV pCCA is accepted as an unresectable disease. In the present study, the results of non-transplant surgical approaches in patients with BC type IV pCCA were examined. Methods Medical records of consecutive patients with BC type IV pCCA between 2010 and 2021 were retrospectively reviewed. Patients were subdivided according to operation type. Postoperative survival rates were compared. Results Hemihepatectomy with caudate lobe and extrahepatic bile duct (EHBD) resection was performed in 15 patients and only EHBD resection was performed in 10 patients. Ten of the cases were found to be unresectable at the stage of laparotomy. Median follow-up was 41.3 (24.8-57.9) months. Overall survival rate for all 35 patients was 56.4% at 1 year, 32.2% at 2 years, and 16.1% at 3 years. When survivals were compared according to operation type, 1, 2, and 3-year survivals were 80%, 57.1% and 42.9% for the hepatectomy group; 55.6%, 44.4% and 11.1% for the EHBD resection group; 75%, 0% and 0% in laparotomy-only group, respectively (p = 0.13). The best survival rates were obtained in patients with pCCA who underwent hepatectomy and were lymph node negative, 100% for 1 year, 66.7 for 2 years and 50% for 3 years. Conclusion It is difficult to achieve high survival rates in BC type IV pCCA. However, these patients mostly benefit from resective treatments. Acceptable survival rates can be achieved, especially in the R0N0 patient group.Öğe The Effect of Pre-transplant Lipid Profile on Post-transplant Hepatocellular Carcinoma Recurrence: Retrospective Single-Center Analysis(Aves, 2022) Ince, Volkan; Carr, Brian, I; Usta, Sertac; Ersan, Veysel; Bag, Harika Gozukara; Yilmaz, SezaiBackground: Plasma lipids have been shown to relate to tumor biology. We aimed to analyze the effect of pre-transplant plasma lipid profiles on post-transplant tumor recurrence in patients with hepatocellular carcinoma and to identify any possible relationship between the pre-transplant lipid profile with maximum tumor diameter, number of tumor nodules, tumor differentiation, portal vein invasion, or serum biomarker levels. Methods: Patients with hepatocellular carcinoma who underwent liver transplants between 2006 and 2021 had data collected prospectively and were analyzed retrospectively. Patients who did not have lipid profile data before transplant and whose post-transplant follow-up period was <90 days were excluded. Patients who had pre-transplant plasma lipid data and whose post-transplant follow-up period was >90 days were included in this study (n = 254). Results: Lower high-density lipoprotein cholesterol levels were found to be significantly associated with post-Tx recurrence (38 vs 29.5, P <.001) and were also significantly associated with macroscopic portal vein thrombosis (39 vs 30.4, P <.021). There was no significant association between plasma lipids and tumor differentiation. Higher high-density lipoprotein cholesterol levels were significantly associated with good overall and disease-free survivals (P =.024 and P =.001). Conclusion: Pre-transplant low plasma high-density lipoprotein cholesterol levels were significantly associated with portal vein thrombosis and poor post-transplant overall and disease-free survivals.Öğe EMT and Inflammation: Crossroads in HCC(Springer, 2023) Sengez, Burcu; Carr, Brian, I; Alotaibi, HaniHepatocellular carcinoma is one of the major causes of cancer-related deaths worldwide and is associated with several inflammatory mediators, since 90% of HCCs occur based on chronic hepatitis B or C, alcoholism or increasingly metabolic syndrome-associated inflammation. EMT is a physiological process, with coordinated changes in epithelial gene signatures and is regulated by multiple factors, including cytokines and growth factors such as TGF beta, EGF, and FGF. Recent reports propose a strong association between EMT and inflammation, which is also correlated with tumor aggressiveness and poor outcomes. Cellular heterogeneity results collectively as an outcome of EMT, inflammation, and the tumor microenvironment, and it plays a fundamental role in the progression, complexity of cancer, and chemoresistance. In this review, we highlight recent developments concerning the association of EMT and inflammation in the context of HCC progression. Identifying potential EMT-related biomarkers and understanding EMT regulatory molecules will likely contribute to promising developments in clinical practice and will be a valuable tool for predicting metastasis in general and specifically in HCC.Öğe Hepatitis B Before and After Hepatocellular Carcinoma(Springer, 2021) Harputluoglu, Murat; Carr, Brian, IHepatitis B virus (HBV) is the one of most common causes of the hepatocellular carcinoma (HCC), especially in eastern world. The aim of this review is to try to understand the relationship between HBV and HCC and to reveal the role of prevention and treatment of HBV infection in reducing the incidence of HCC. Strategies to prevent HCC due to HBV can be classified into three categories. These are primary, secondary, and tertiary preventions. Hepatitis B vaccine is now in the most vital position in preventing HBV-associated HCC. In patients with chronic hepatitis B infection, suppressing viral load with potent antivirals such as tenofovir disoproxil fumarate (TDF) and entecavir (ETV) prevents the development of HCC and improves prognosis by reducing recurrence after HCC treatments. There is currently no clear consensus on which of these drugs should be preferred. Although data on tenofovir alafenamide (TAF) are scarce, available data with TDF suggest that TAF therapy will also be a strong actor for HCC.Öğe Liver transplant for large hepatocellular carcinoma in Malatya: The role of gamma glutamyl transferase and alpha-fetoprotein, a retrospective cohort study(Baishideng Publishing Group Inc, 2020) Ince, Volkan; Carr, Brian, I; Bag, Harika Gozukara; Ersan, Veysel; Usta, Sertac; Koc, Cemalettin; Gonultas, FatihBACKGROUND There is increasing interest in transplanting patients with hepatocellular carcinoma (HCC) with tumors greater than 5 cm (Milan criteria). AIM To investigate possible prognostically-useful factors for liver transplantation in HCC patients with large tumors. METHODS In this clinical study, 50 patients with HCC who were transplanted at our Liver Transplant Center between April 2006 and August 2019 and had tumors greater than 6 cm maximum diameter were retrospectively analyzed. Their survival and full clinical characteristics were examined, with respect to serum alpha-fetoprotein (AFP) and gamma glutamyl transpeptidase (GGT) levels. Kaplan-Meier survival estimates were used to determine overall survival and disease-free survival in these patients. The inclusion criterion was evidence of HCC. Exclusion criteria were the presence of macroscopic portal vein thrombosis or metastasis and a follow-up period of less than 90 d. RESULTS Using receiver operating characteristic curve (ROC) analysis, cutoff values of AFP 200 ng/mL and GGT 104 IU/L were identified and used in this study. Significantly longer overall survival (OS) and disease-free-survival (DFS) were found in patients who had lower values of either parameter, compared with higher values. Even greater differences in survival were found when the 2 parameters were combined. Two tumor size bands were identified, in searching for the limits of this approach with larger tumors, namely 6-10 cm and > 10 cm. Combination parameters in the 6-10 cm band reflected 5-year OS of 76.2% in patients with low AFP plus low GGT vs 0% for all other groups. Patients with tumors greater than 10 cm, did not have low AFP plus low GGT. The most consistent clinical correlates for longer survival were degree of tumor differentiation and absence of microscopic portal venous invasion. CONCLUSION Serum levels of AFP and GGT, both alone and combined, represent a simple prognostic identifier in patients with large HCCs undergoing liver transplant-ation.Öğe Liver Transplantation for Hepatocellular Carcinoma: Malatya Experience and Proposals for Expanded Criteria(Springer, 2020) Ince, Volkan; Akbulut, A. Sami; Otan, Emrah; Ersan, Veysel; Karakas, Serdar; Sahin, Tolga Tevfik; Carr, Brian, ISurvival was examined from a Turkish liver transplant center of patients with HCC, to identify prognostic factors. Data from 215 patients who underwent predominantly live donor liver transplant for HCC at our institute over 12 years were included in the study and prospectively recorded. They were 152 patients within and 63 patients beyond Milan criteria. Patients beyond Milan criteria were divided into two groups according to presence or absence of tumor recurrence. Recurrence-associated factors were analyzed. These factors were then applied to the total cohort for survival analysis. We identified four factors, using multivariate analysis, that were significantly associated with tumor recurrence. These were maximum tumor diameter, degree of tumor differentiation, and serum AFP and GGT levels. A model that included all four of these factors was constructed, the 'Malatya criteria.' Using these Malatya criteria, we estimated DFS and cumulative survival, for patients within and beyond these criteria, and found statistically significant differences with improved survival in patients within Malatya criteria of 1, 5, and 10-year overall survival rates of 90.1%, 79.7%, and 72.8% respectively, which compared favorably with other extra-Milan extended criteria. Survival of our patients within the newly defined Malatya criteria compared favorably with other extra-Milan extended criteria and highlight the usefulness of serum AFP and GGT levels in decision-making.Öğe Liver Transplantation for Hepatocellular Carcinoma: Malatya Experience and Proposals for Expanded Criteria (vol 56, pg 331, 220)(Springer, 2020) Ince, Volkan; Akbulut, Sami; Otan, Emrah; Ersan, Veysel; Karakas, Serdar; Sahin, Tolga Tevfik; Carr, Brian, IThe original version of this article unfortunately contained a mistake in the author group section.Öğe Microscopic Portal Vein Invasion in Relation to Tumor Focality and Dimension in Patients with Hepatocellular Carcinoma(Springer, 2022) Carr, Brian, I; Guerra, Vito; Donghia, Rossella; Ince, Volkan; Akbulut, Sami; Ersan, Veysel; Usta, SertacBackground Microscopic portal vein invasion (microPVI) and tumor multifocality are hepatocellular carcinoma (HCC) prognosis factors. To investigate whether microPVI and multifocality are directly related to each other. Methods We retrospectively analyzed the relationships between microPVI, multifocality, and maximum tumor diameter (MTD) in prospectively collected transplanted HCC patients. Results HCCs with 1, 2, or >= 3 foci had more microPVI in larger than in smaller HCCs, with microPVI being present in 52.24% of single large foci. Conversely, microPVI patients had similar percentages of single and multifocal lesions. A linear regression model of MTD, showed microPVI best associated with MTD, with 2.49 as coefficient, whereas multifocality had a 0.83 coefficient. A logistic regression model of microPVI showed significant association with tumor multifocality, especially for small HCCs. Trends for microPVI and multifocality in relation to MTD revealed that both increased with MTD but more significantly for microPVI. Survival was similar in patients with small HCCs, with or without microPVI, but was significantly worse in microPVI patients with larger HCCs. No patient survival differences were found in relation to focality. Conclusions MTD had stronger associations with microPVI than with multifocality. microPVI was associated with worse survival in patients with large HCCs, but survival was not impacted by number of tumor foci. microPVI and multifocality appear weakly related, having different behavior in relation to MTD and survival.Öğe Platelet-to-lymphocyte and neutrophil-to-lymphocyte ratios predict tumor size and survival in HCC patients: Retrospective study(Elsevier Sci Ltd, 2020) Suner, Asli; Carr, Brian, IBackground: Inflammation is a recognized concomitant of hepatocellular carcinoma (HCC) and its indices are prognostically useful. Aims: To evaluate two commonly used inflammatory indices, neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR), to examine their relationship to maximum tumor diameter (MTD) and to survival. Methods: A database of 1024 prospectively-accrued HCC patients was examined, who had full baseline tumor parameter data, including CT scan information on HCC size and whose survival was known. Analyses of NLR and PLR were correlated to MDT and to survival. NLR and PLR cutoffs were calculated from receiver operator characteristic curves. Results: Every MTD pair had significantly different PLR values, for MTD groups of groups <2/>= 2, <3/>= 3, <4/>= 4, <5/>= 5 cm. However there were few significant differences in NLR values. Logistic regression models of different MTD groups likewise showed significance for PLR. Patients with both low NLR and low PLR had the longest overall survival compared to all the other 3 combinations of NLR and PLR. In a Cox regression analysis, univariate models on NLR (<= 3.02/>3.02) and PLR (<= 6.82/>6.82) groups, showed significance for PLR, p = 0.034 and approaching significance for NLR, p = 0.057. Conclusions: MTD pairs down to <2/>= 2 cm showed significance for PLR, survival showed significance for PLR and almost for NLR.