Publications by authors named "Myron E Schwartz"

77 Publications

Outcomes of liver transplantation for nonalcoholic steatohepatitis-associated hepatocellular carcinoma.

HPB (Oxford) 2021 Sep 6. Epub 2021 Sep 6.

Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Background: Nonalcoholic steatohepatitis-associated hepatocellular carcinoma (NASH-HCC) is the second-leading cause of liver transplantation (LT) performed for HCC. Despite this, little is known about the clinical characteristics and outcomes of NASH-HCC.

Methods: Patients undergoing LT for HCC from 2001 to 2017 at a single center were reviewed. Outcomes of NASH-HCC (n = 51) were compared to other etiologies of HCC including hepatitis C (HCV) hepatitis B (HBV), and alcoholic liver disease (ALD). Outcomes of NASH-HCC were also compared to HCV in the direct-acting antiviral (DAA) era (2014-2017).

Results: The frequency of NASH-HCC as the primary indication for LT in patients with HCC increased significantly during the study period from 4.4% (2001-2008) to 15.6% in 2017. NASH-HCC patients were significantly older (median age 65 vs. 60; P < 0.001) with significantly lower alpha-fetoprotein levels (7.5 vs. 26.5, P < 0.001) compared to other etiologies. The 1-, 3-, and 5-year overall survival of NASH-HCC was 92%, 86%, and 80%. Overall survival of NASH-HCC was not significantly different compared to HCV, HBV, or ALD. Compared to HCV-HCC in the DAA era (n = 99), NASH-HCC had comparable post-LT survival (3-year survival 87% vs. 86%, P = 0.870).

Conclusion: In this large single-center experience of NASH-HCC, we demonstrate favorable outcomes of NASH-HCC following LT comparable to other common etiologies of HCC.
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http://dx.doi.org/10.1016/j.hpb.2021.08.943DOI Listing
September 2021

A human liver cell-based system modeling a clinical prognostic liver signature for therapeutic discovery.

Nat Commun 2021 09 17;12(1):5525. Epub 2021 Sep 17.

Liver Tumor Translational Research Program, Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Chronic liver disease and hepatocellular carcinoma (HCC) are life-threatening diseases with limited treatment options. The lack of clinically relevant/tractable experimental models hampers therapeutic discovery. Here, we develop a simple and robust human liver cell-based system modeling a clinical prognostic liver signature (PLS) predicting long-term liver disease progression toward HCC. Using the PLS as a readout, followed by validation in nonalcoholic steatohepatitis/fibrosis/HCC animal models and patient-derived liver spheroids, we identify nizatidine, a histamine receptor H2 (HRH2) blocker, for treatment of advanced liver disease and HCC chemoprevention. Moreover, perturbation studies combined with single cell RNA-Seq analyses of patient liver tissues uncover hepatocytes and HRH2, CLEC5A, MARCO liver macrophages as potential nizatidine targets. The PLS model combined with single cell RNA-Seq of patient tissues enables discovery of urgently needed targets and therapeutics for treatment of advanced liver disease and cancer prevention.
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http://dx.doi.org/10.1038/s41467-021-25468-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448834PMC
September 2021

PD-1 inhibitor as bridge therapy to liver transplantation?

Am J Transplant 2021 05 2;21(5):1979-1980. Epub 2021 Jan 2.

Mount Sinai Medical Center, Recanati/Miller Transplantation Institute, New York, New York.

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http://dx.doi.org/10.1111/ajt.16448DOI Listing
May 2021

Inpatient Specialty-Level Palliative Care Is Delivered Late in the Course of Hepatocellular Carcinoma and Associated With Lower Hazard of Hospital Readmission.

J Pain Symptom Manage 2021 05 6;61(5):940-947.e3. Epub 2020 Oct 6.

Boston Veterans Affairs Healthcare System, Boston, Massachusetts, USA; Department of Health Law, Policy and Management, Boston University School of Public Health, Boston, Massachusetts, USA.

Context: Little is known about receipt of specialty-level palliative care by people with hepatocellular carcinoma (HCC) or its impact on health care utilization.

Objectives: Identify patient characteristics associated with receipt of specialty-level palliative care among hospitalized HCC patients and measure association with time to readmission.

Methods: We used logistic regression to examine relationships between receipt of inpatient palliative care consultation by HCC patients at an academic center (N = 811; 2012-2016) and clinical and demographic covariates at index hospitalization. We used a survival analysis model accounting for competing risk of mortality to compare time to readmission among individuals who did or did not receive palliative care during the admission and performed a sensitivity analysis using kernel weights to account for selection bias.

Results: Overall, 16% received inpatient palliative care consults. Those who received consults had worse laboratory values than those who did not. In a multivariable model, higher Model for End-Stage Liver Disease Sodium, receipt of sorafenib, and higher pain scores were significantly associated with increased odds of palliative care, whereas liver transplantation and admission to a surgical service were associated with lower odds. For time to readmission (2076 hospitalizations for 811 individuals with 175 palliative care visits), the subhazard ratio for readmission for patients who received consults was 0.26 (95% CI = 0.18-0.38) and 0.35 (95% CI = 0.24-0.52) with a kernel-weighted sample.

Conclusion: Inpatient palliative care consultation was received by individuals with more advanced disease and associated with lower readmission hazard. These findings support further research and the development of HCC-specific programs that increase access to specialty-level palliative care.
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http://dx.doi.org/10.1016/j.jpainsymman.2020.09.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021616PMC
May 2021

Morphology of tumor and nontumor tissue in liver resection specimens for hepatocellular carcinoma following nivolumab therapy.

Mod Pathol 2021 04 28;34(4):823-833. Epub 2020 Sep 28.

Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Nivolumab is an immune checkpoint inhibitor (ICI) approved for treatment of many cancers, including hepatocellular carcinoma (HCC). Liver injury is a known complication in patients treated with nivolumab for nonliver tumors. To date, the morphologic changes to tumor and nontumor liver have not been well-characterized in HCC patients. We identified 20 patients who underwent partial hepatectomy or liver transplantation after receiving nivolumab for HCC. Demographics, laboratory values, and imaging results were obtained from medical records. All available slides from resection specimens were evaluated for tumor necrosis, tumor-infiltrating lymphocytes (TILs), and features of liver injury. Patients in the study included 16 males and 4 females with median age of 56 years. The underlying liver disease was HBV in 10, HCV in 6, and unknown/other in 4. Twelve patients were treated with nivolumab in the neoadjuvant setting, whereas eight were treated with nivolumab, usually along with other therapies, before undergoing liver transplantation. On review of resection specimens, three patients (all from the neoadjuvant group) demonstrated marked treatment response attributable to nivolumab. TILs were present in 17/20 cases. One case that showed treatment response in the neoadjuvant group demonstrated non-necrotizing granulomas and prominent bile duct intraepithelial lymphocytes (IELs) in the nontumor liver. One case from the transplant group showed bile duct damage and prominent ductular reaction after long-term nivolumab therapy (32 doses). Our findings indicate that nivolumab is effective in a subset of patients, including in the neoadjuvant setting. Granulomas and bile duct IELs are rare findings in cases treated with nivolumab but, when seen, may indicate potential response to therapy. Bile duct damage and ductular reaction may be manifestations of long-term nivolumab therapy. Future prospective and longitudinal studies with pretreatment tumor biopsies may help identify patients apt to respond to ICI therapy and further characterize patterns of ICI-related liver injury.
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http://dx.doi.org/10.1038/s41379-020-00679-5DOI Listing
April 2021

Von Meyenburg complexes: a rare intrahepatic bile duct malformation.

Minerva Chir 2020 08 26;75(4):272-274. Epub 2020 May 26.

Mount Sinai Liver Cancer Program, Mount Sinai Medical Center, New York, NY, USA.

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http://dx.doi.org/10.23736/S0026-4733.20.08285-1DOI Listing
August 2020

Resection of Mixed Hepatocellular-Cholangiocarcinoma, Hepatocellular Carcinoma, and Intrahepatic Cholangiocarcinoma.

Liver Transpl 2020 07;26(7):888-898

Liver Cancer Program, Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY.

Mixed hepatocellular-cholangiocarcinoma (HCC-CC) is a biphenotypic liver cancer thought to have unfavorable tumor biology and a poor prognosis. Surgical outcomes of HCC-CC remain unclear. We aimed to evaluate the clinical characteristics and surgical outcomes of HCC-CC. We analyzed a series of patients undergoing resection for HCC-CC (n = 47), hepatocellular carcinoma (HCC; n = 468), and intrahepatic cholangiocarcinoma (ICC; n = 108) at a single Western center between 2001 and 2015. Patients with HCC-CC were matched to patients with HCC and ICC on important clinical factors including tumor characteristics (size, vascular invasion, and differentiation) and underlying cirrhosis. Patients with HCC-CC had rates of viral hepatitis comparable to patients with HCC (78.7% versus 80.0%), and 42.5% had underlying cirrhosis. When matched on tumor size, HCC-CC was more poorly differentiated than HCC (68.3% versus 27.3%; P < 0.001) and ICC (68.3% versus 34.8%; P = 0.01) but had similar postresection survival (5-year survival: HCC-CC 49.7%, HCC 54.8%, ICC 68.7%; P = 0.61) and recurrence (3-year recurrence: HCC-CC 57.9%, HCC 61.5%, and ICC 56%; P = 0.58). Outcomes were similar between HCC-CC and HCC when matched on underlying cirrhosis and tumor size. Cancer type was not predictive of survival or tumor recurrence. Survival after resection of HCC-CC is similar to HCC when matched for tumor size, despite HCC-CC tumors being more poorly differentiated. Exclusion of HCC-CC from management strategies recommended for HCC, including consideration for liver transplantation, may not be warranted.
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http://dx.doi.org/10.1002/lt.25786DOI Listing
July 2020

Abdominal Tuberculosis Mimicking Cancer Clinically and on Fluorodeoxyglucose (FDG)-Positron Emission Tomography (PET) Imaging: A Two-Case Series.

Am J Case Rep 2020 Feb 5;21:e918901. Epub 2020 Feb 5.

Liver Surgery at Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.

BACKGROUND Miliary tuberculosis (MT) is the disseminated form of tuberculosis (TB) and it is a potentially fatal condition. Diagnosis is often delayed because symptoms are typically nonspecific or absent, and misdiagnosis in favor of other diseases is common. We report 2 cases of disseminated TB that were diagnosed during or after surgeries performed for other suspected diseases. CASE REPORT Imaging findings are not specific and cannot be relied upon to raise suspicion of MT. In the first case, besides other imaging techniques, we also performed a positron emission tomography-computed tomography (PET-CT) on the patient and the resulting, thick, fluorodeoxyglucose (FDG)-avid ring surrounding the liver first led to concern for peritoneal carcinomatosis. TB peritonitis was only identified on laparoscopy and biopsy. In the second case, CT and magnetic resonance imaging (MRI) findings of a solitary liver mass with an irregular enhancing rim and progressive enhancement led to a radiographic diagnosis of likely intrahepatic cholangiocarcinoma, The subsequent finding that the lesion was intensely FDG-avid without other foci of FDG uptake led to the decision to proceed with resection without a prior biopsy. CONCLUSIONS We have presented 2 patients with TB in whom clinical and imaging findings, and in particular, FDG-PET imaging, led to an erroneous clinical diagnosis of malignancy. An awareness that TB remains very much an active clinical problem in North America and that there are other reasons for FDG uptake on PET imaging besides cancer, is necessary in order to avoid unnecessary and potentially deleterious interventions in patients with TB.
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http://dx.doi.org/10.12659/AJCR.918901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020736PMC
February 2020

HIV infection modulates IL-1β response to LPS stimulation through a TLR4-NLRP3 pathway in human liver macrophages.

J Leukoc Biol 2019 04 18;105(4):783-795. Epub 2019 Feb 18.

Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

IL-1β is an important mediator of innate inflammatory responses and has been shown to contribute to liver injury in a number of etiologies. HIV patients have increased necroinflammation and more rapid fibrosis progression in chronic liver injury compared to non-HIV-infected patients. As the resident liver macrophage is critical to the IL-1β response to microbial translocation in chronic liver disease, we aim to examine the impact of HIV-1 and LPS stimulation on the IL-1β response of the resident hepatic macrophages. We isolated primary human liver macrophages from liver resection specimens, treated them with HIV-1 and/or LPS ex vivo, examined the IL-1β response, and then studied underlying mechanisms. Furthermore, we examined IL-1β expression in liver tissues derived from HIV-1 patients compared to those with no underlying liver disease. HIV-1 up-regulated TLR4 and CD14 expression on isolated primary CD68+ human liver macrophages and contributed to the IL-1β response to LPS stimulation as evidenced by TLR4 blocking. Nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) was shown to be involved in the IL-1β response of liver macrophages to HIV-1 infection and NLRP3 blocking experiments in primary CD68+ liver macrophages confirmed the contribution of the NLRP3-caspase 1 inflammatory signaling pathway in the IL-1β response. High in situ IL-1β expression was found in CD68 cells in human liver tissues from HIV-1-infected patients, suggesting a critical role of IL-1β responses in patients infected by HIV. HIV infection sensitizes the IL-1β response of liver macrophages to LPS through up-regulation of CD14 and TLR4 expression and downstream activation of the NLRP3-caspase 1 pathway. These findings have implications for enhanced immune activation in HIV patients and mechanisms for rapid fibrosis progression in patients with chronic liver injury.
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http://dx.doi.org/10.1002/JLB.4A1018-381RDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685708PMC
April 2019

At diagnosis of hepatocellular carcinoma, African Americans with hepatitis C have better liver function than other patients.

Clin Liver Dis (Hoboken) 2018 Oct 6;12(4):109-112. Epub 2018 Nov 6.

Department of Medicine, Division of Liver Diseases, Icahn School of Medicine at Mount Sinai Medical Center, New York, NY.

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http://dx.doi.org/10.1002/cld.745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220896PMC
October 2018

Sex difference in recurrence and survival after liver resection for hepatocellular carcinoma: A multicenter study.

Surgery 2019 03 15;165(3):516-524. Epub 2018 Oct 15.

Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China; Liver Cancer Program, Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address:

Background: There is a striking sex difference in the incidence of hepatocellular carcinoma, with a strong predominance for men; however, the impact of sex on the incidence of recurrence after curative resection of hepatocellular carcinoma remains controversial. This study aimed to assess sex differences in the risks of recurrence and mortality for patients treated with curative resection of hepatocellular carcinoma.

Methods: We retrospectively reviewed data from 1,435 hepatocellular carcinoma patients treated with curative resection (1,228 men and 207 women) between 2004 and 2014 at 5 institutions in China. Patients' baseline characteristics, operative variables, and rates of early recurrence (≤2 years after resection), late recurrence (>2 years after resection), and cancer-specific mortality were evaluated and compared. To clarify the true oncologic impact of sex, multivariable competing-risks regression analyses were performed to identify predictors associated with early and late recurrence, as well as cancer-specific mortality.

Results: The early recurrence rates between men and women were similar (43.3% vs 42.0%, P = .728), but the late recurrence and rates of cancer-specific mortality in men were greater compared with women (17.2% vs 11.2%, P = .044; and 42.8% vs 34.3%, P = .022, respectively). Multivariable competing-risks regression analyses revealed no sex difference in early recurrence; however, men had greater late recurrence rate (hazard ratio, 1.752; 95% confidence interval, 1.145-2.682; P = .010) and rate of cancer-specific mortality (hazard ratio, 1.307; 95% confidence interval, 1.015-1.683; P = .038).

Conclusion: There was no difference in early recurrence rate (≤2 years after resection between men and women, but men had significantly greater late recurrence (>2 years) and rates of cancer-specific mortality after hepatocellular carcinoma resection than women.
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http://dx.doi.org/10.1016/j.surg.2018.08.031DOI Listing
March 2019

Trunk mutational events present minimal intra- and inter-tumoral heterogeneity in hepatocellular carcinoma.

J Hepatol 2017 12 24;67(6):1222-1231. Epub 2017 Aug 24.

Mount Sinai Liver Cancer Program (Divisions of Liver Diseases, Department of Medicine, Department of Pathology, Recanati Miller Transplantation Institute), Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, USA; Liver Cancer Translational Research Laboratory, BCLC Group, IDIBAPS, Liver Unit, Hospital Clinic, University of Barcelona, Barcelona, Catalonia, Spain; Institució Catalana de Recerca i Estudis Avançats, Barcelona, Catalonia, Spain. Electronic address:

Background & Aims: According to the clonal model of tumor evolution, trunk alterations arise at early stages and are ubiquitous. Through the characterization of early stages of hepatocarcinogenesis, we aimed to identify trunk alterations in hepatocellular carcinoma (HCC) and study their intra- and inter-tumor distribution in advanced lesions.

Methods: A total of 151 samples representing the multistep process of hepatocarcinogenesis were analyzed by targeted-sequencing and a single nucleotide polymorphism array. Genes altered in early lesions (31 dysplastic nodules [DNs] and 38 small HCCs [sHCC]) were defined as trunk. Their distribution was explored in: a) different regions of large tumors (43 regions, 21 tumors), and b) different nodules of the same patient (39 tumors, 17 patients). Multinodular lesions were classified as intrahepatic metastases (IMs) or synchronous tumors based on chromosomal aberrations.

Results: TERT promoter mutations (10.5%) and broad copy-number aberrations in chromosomes 1 and 8 (3-7%) were identified as trunk gatekeepers in DNs and were maintained in sHCCs. Trunk drivers identified in sHCCs included TP53 (23%) and CTNNB1 (11%) mutations, and focal amplifications or deletions in known drivers (6%). Overall, TERT, TP53 and CTNNB1 mutations were the most frequent trunk events and at least one was present in 51% of sHCCs. Around 90% of mutations in these genes were ubiquitous among different regions of large tumors. In multinodular HCCs, 35% of patients harbored IMs; 85% of mutations in TERT, TP53 and/or CTNNB1 were retained in primary and metastatic tumors.

Conclusions: Trunk events in early stages (TERT, TP53, CTNNB1 mutations) were ubiquitous across different regions of the same tumor and between primary and metastatic nodules in >85% of cases. This concept supports the knowledge that single biopsies would suffice to capture trunk mutations in HCC.

Lay Summary: Trunk alterations arise at early stages of cancer and are shared among all malignant cells of the tumor. In order to identify trunk alterations in HCC, we characterized early stages of hepatocarcinogenesis represented by dysplastic nodules and small lesions. Mutations in TERT, TP53 and CTNNB1 genes were the most frequent. Analyses in more advanced lesions showed that mutations in these same genes were shared between different regions of the same tumor and between primary and metastatic tumors, suggesting their trunk role in this disease.
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http://dx.doi.org/10.1016/j.jhep.2017.08.013DOI Listing
December 2017

Comparison of Patterns and Outcomes of Liver Resection for Hepatocellular Carcinoma: East vs West.

Clin Gastroenterol Hepatol 2017 12 17;15(12):1972-1974. Epub 2017 Jun 17.

Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China. Electronic address:

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http://dx.doi.org/10.1016/j.cgh.2017.06.025DOI Listing
December 2017

Radioembolization for Unresectable Intrahepatic Cholangiocarcinoma: Review of Safety, Response Evaluation Criteria in Solid Tumors 1.1 Imaging Response and Survival.

Cancer Biother Radiopharm 2017 Jun 9;32(5):161-168. Epub 2017 Jun 9.

3 Division of Interventional Radiology, Department of Radiology, Icahn School of Medicine at Mount Sinai , New York, New York.

The optimal palliative treatment for unresectable intrahepatic cholangiocarcinoma (ICC) remains controversial. While selective internal radiation therapy (SIRT) using yttrium-90 microspheres is a well-accepted treatment for hepatocellular carcinoma, data related to its use for locally advanced ICC remain relatively scarce. Twenty-nine patients (mean age 66 ± 11 years; 15 female) with unresectable biopsy-proven ICC treated with SIRT between June 2008 and April 2015 were retrospectively evaluated for post-treatment toxicity, overall survival, and imaging response using response evaluation criteria in solid tumors (RECIST) 1.1 criteria. RECIST 1.1 response was evaluable following 26 treatments [complete response (CR):0, partial response (PR):3; stable disease (SD):16, progression of disease (PD):7]. Objective response rate (CR+PR) was 12%. Disease control rate (CR+PR+SD) was 73%. Median time to progression was 5.6 [95% confidence interval (CI): 0-12.0] months. Median survival following SIRT was 9.1 (95% CI: 1.7-16.4) months. Post-treatment survival was prolonged in patients with absence of extrahepatic disease (p = 0.03) and correlated with RECIST 1.1 response (p = 0.02). Toxicities were limited to grade I severity and occurred following 27% of treatments. These findings support the safe, effective use of SIRT for unresectable ICC. Post-treatment survival is prolonged in patients with absence of extrahepatic disease at baseline. RECIST 1.1 response following SIRT for ICC is predictive of survival.
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http://dx.doi.org/10.1089/cbr.2017.2189DOI Listing
June 2017

Mixed hepatocellular cholangiocarcinoma tumors: Cholangiolocellular carcinoma is a distinct molecular entity.

J Hepatol 2017 05 23;66(5):952-961. Epub 2017 Jan 23.

Liver Cancer Translational Research Laboratory, Liver Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, CIBERehd, Universitat de Barcelona, Barcelona, Catalonia, Spain; Mount Sinai Liver Cancer Program, (Divisions of Liver Diseases, Hematology and Medical Oncology, Department of Medicine, Department of Pathology, Recanati Miller Transplantation Institute), Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, USA; Institució Catalana de Recerca i Estudis Avançats, Barcelona, Catalonia, Spain. Electronic address:

Background & Aims: Mixed hepatocellular cholangiocarcinoma (HCC-CCA) is a rare and poorly understood type of primary liver cancer. We aimed to perform a comprehensive molecular characterization of this malignancy.

Methods: Gene expression profiling, DNA copy number detection, and exome sequencing using formalin-fixed samples from 18 patients with mixed HCC-CCA were performed, encompassing the whole histological spectrum of the disease. Comparative genomic analysis was carried out, using independent datasets of HCC (n=164) and intrahepatic cholangiocarcinoma (iCCA) (n=149).

Results: Integrative genomic analysis of HCC-CCAs revealed that cholangiolocellular carcinoma (CLC) represents a distinct biliary-derived entity compared with the stem-cell and classical types. CLC tumors were neural cell adhesion molecule (NCAM) positive (6/6 vs. 1/12, p<0.001), chromosomally stable (mean chromosomal aberrations 5.7 vs. 14.1, p=0.008), showed significant upregulation of transforming growth factor (TGF)-β signaling and enrichment of inflammation-related and immune response signatures (p<0.001). Stem-cell tumors were characterized by spalt-like transcription factor 4 (SALL4) positivity (6/8 vs. 0/10, p<0.001), enrichment of progenitor-like signatures, activation of specific oncogenic pathways (i.e., MYC and insulin-like growth factor [IGF]), and signatures related to poor clinical outcome. In the classical type, there was a significant correlation in the copy number variation of the iCCA and HCC components, suggesting a clonal origin. Exome sequencing revealed an average of 63 non-synonymous mutations per tumor (2 mean driver mutations per tumor). Among those, TP53 was the most frequently mutated gene (6/21, 29%) in HCC-CCAs.

Conclusions: Mixed HCC-CCA represents a heterogeneous group of tumors, with the stem-cell type characterized by features of poor prognosis, and the classical type with common lineage for HCC and iCCA components. CLC stands alone as a distinct biliary-derived entity associated with chromosomal stability and active TGF-β signaling.

Lay Summary: Molecular analysis of mixed hepatocellular cholangiocarcinoma (HCC-CCA) showed that cholangiolocellular carcinoma (CLC) is distinct and biliary in origin. It has none of the traits of hepatocellular carcinoma (HCC). However, within mixed HCC-CCA, stem-cell type tumors shared an aggressive nature and poor outcome, whereas the classic type showed a common cell lineage for both the HCC and the intrahepatic CCA component. The pathological classification of mixed HCC-CCA should be redefined because of the new molecular data provided.
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http://dx.doi.org/10.1016/j.jhep.2017.01.010DOI Listing
May 2017

Disentangling the effects of race and socioeconomic factors on liver transplantation rates for hepatocellular carcinoma.

Clin Transplant 2016 06 30;30(6):714-21. Epub 2016 Apr 30.

The Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Introduction: Liver transplantation is the most effective treatment for hepatocellular carcinoma (HCC) in eligible patients, but is not accessed equally by all. We explored the effects of race and socioeconomic factors on transplantation for HCC while controlling for stage, resection status, and transplant candidacy.

Patients And Methods: All HCC patients, 2003-2013, were retrospectively analyzed using multivariate analysis to explore differences in transplantation rates among cohorts.

Results: Of 3078 HCC patients, 754 (24%) were considered transplant eligible. Odds of transplantation were significantly higher for those with commercial insurance (OR = 1.99, 95% CI [1.42, 2.79]) and lower for black patients (OR = 0.55, 95% CI [0.33, 0.91]). Asians were more likely to be resected than white patients with similarly staged tumors and transplant criteria (p < 0.001). Patients not listed for transplantation for non-medical reasons were more likely to be government-insured (p = 0.02) and not white (p = 0.05). No step along the transplantation pathway was identified as the dominant hurdle.

Discussion: Patients who are black or government-insured are significantly less likely to undergo transplantation for HCC despite controlling for tumor stage, resection status, and transplant eligibility. Asian patients have higher rates of hepatic resection, but also appear to have lower transplantation rates beyond this effect.
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http://dx.doi.org/10.1111/ctr.12739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4899088PMC
June 2016

Ectopic lymphoid structures function as microniches for tumor progenitor cells in hepatocellular carcinoma.

Nat Immunol 2015 Dec 26;16(12):1235-44. Epub 2015 Oct 26.

Department of Immunology and Cancer Research, Institute for Medical Research Israel Canada, Hebrew University-Hadassah Medical School, Jerusalem, Israel.

Ectopic lymphoid-like structures (ELSs) are often observed in cancer, yet their function is obscure. Although ELSs signify good prognosis in certain malignancies, we found that hepatic ELSs indicated poor prognosis for hepatocellular carcinoma (HCC). We studied an HCC mouse model that displayed abundant ELSs and found that they constituted immunopathological microniches wherein malignant hepatocyte progenitor cells appeared and thrived in a complex cellular and cytokine milieu until gaining self-sufficiency. The egress of progenitor cells and tumor formation were associated with the autocrine production of cytokines previously provided by the niche. ELSs developed via cooperation between the innate immune system and adaptive immune system, an event facilitated by activation of the transcription factor NF-κB and abolished by depletion of T cells. Such aberrant immunological foci might represent new targets for cancer therapy.
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http://dx.doi.org/10.1038/ni.3290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4653079PMC
December 2015

Liver transplantation for metastatic neuroendocrine tumors: Outcomes and prognostic variables.

J Surg Oncol 2015 Aug 14;112(2):125-32. Epub 2015 Jul 14.

Department of Surgery, Recanati/Miller Transplantation Institute Icahn School of Medicine at Mount Sinai, New York, New York.

Background: Patient selection for liver transplantation for metastatic neuroendocrine tumors remains a topic of debate. There is no established MELD exception, making it difficult to obtain donor organs.

Methods: A multicenter database was created assessing outcomes for liver and multivisceral transplantation for metastatic neuroendocrine tumors and identifying prognostic factors for survival. Demographic, transplant, primary tumor site and management, pathology, recurrent disease and survival data were collected and analyzed. Survival probabilities were calculated using the Kaplan-Meier method.

Results: Analysis included 85 patients who underwent liver transplantation November 1988-January 2012 at 28 centers. One, three, and five-year patient survival rates were 83%, 60%, and 52%, respectively; 40 of 85 patients died, with 20 of 40 deaths due to recurrent disease. In univariate analyses, the following were predictors of poor prognosis: large vessel invasion (P < 0.001), extent of extrahepatic resection at liver transplant (P = 0.007), and tumor differentiation (P = 0.003). In multivariable analysis, predictors of poor overall survival included large vessel invasion (P = 0.001), and extent of extrahepatic resection at liver transplant (P = 0.015).

Conclusion: In the absence of poor prognostic factors, metastatic neuroendocrine tumor is an acceptable indication for liver transplantation. Identification of favorable prognostic factors should allow assignment of a MELD exception similar to hepatocellular carcinoma.
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http://dx.doi.org/10.1002/jso.23973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492100PMC
August 2015

Reporting and methodological qualities of published surgical meta-analyses.

J Clin Epidemiol 2016 Feb 24;70:4-16. Epub 2015 Jun 24.

Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No. 225 Changhai Road, Shanghai 200438, China; Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, 5 East 98th Street, 12th Floor, New York, NY 10029, USA. Electronic address:

Objectives: To assess the overall qualities of published surgical meta-analysis and predictive factors for high qualities.

Study Design And Setting: All meta-analyses pertinent to surgical procedures published in year 2013 were selected from PubMed and EMBASE. The characteristics of the included meta-analyses were collected, and their reporting and methodologic qualities were assessed by the PRISMA (27 items) and AMSTAR (11 items) checklists, respectively. Independent predictive factors associated with these two qualities were evaluated by univariate and multivariate analyses.

Results: Hundred ninety-seven meta-analyses representing 10 surgical subspecialties were included. The mean PRISMA and AMSTAR adherences (by items) were 22.2 ± 2.4 and 7.8 ± 1.2, respectively, and a positive linear correlation was found between them with an R(2) of 0.793. Those meta-analyses conducted by the first authors having meta-analysis publication previously had significantly higher reporting and methodologic qualities than those who did not (P = 0.002 and P = 0.001). Meanwhile, there were also significant differences in these two qualities between studies published in Q1-ranked and (Q2 + Q3)-ranked journals as rated by the SCImago indicator (P < 0.001 and P < 0.001). On multivariate analyses, region of origin (non-Asia vs. Asia), publishing experience of first authors (ever vs. never), rank of publishing journals (Q1 vs. Q2 + Q3), and preregistration (presence vs. absence) were independently associated with superior reporting and methodologic qualities.

Conclusions: The reporting and methodologic qualities of current surgical meta-analyses remained suboptimal, and first authors' experience and ranking of publishing journals were independently associated with both qualities. Preregistration might be an effective measure to improve the quality of meta-analyses, which deserves more attention from future study conductors.
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http://dx.doi.org/10.1016/j.jclinepi.2015.06.009DOI Listing
February 2016

Perioperative blood transfusion and long-term outcomes after resection of hilar cholangiocarcinoma.

J Gastrointest Surg 2015 Jun 21;19(6):1192-3. Epub 2015 Apr 21.

Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China.

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http://dx.doi.org/10.1007/s11605-015-2822-3DOI Listing
June 2015

Comparative study of living and deceased donor liver transplantation as a treatment for hepatocellular carcinoma.

J Am Coll Surg 2015 Mar 13;220(3):297-304.e3. Epub 2014 Dec 13.

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Background: Living donor liver transplantation (LDLT) is an important treatment option for unresectable hepatocellular carcinoma (HCC), but whether recurrence and survival in LDLT differ from those in deceased donor liver transplantation (DDLT) remains controversial.

Study Design: A retrospective analysis was performed between patients with HCC who underwent LDLT in a Japanese institute (n = 133) and those who underwent DDLT in a United States institute (n = 362).

Results: Although there was a difference in patient background characteristics (eg, body mass index, donor age, Model for End-Stage Liver Disease [MELD] score), tumor aggressiveness represented by Milan criteria and microscopic vascular invasion were comparable between the 2 groups. The cumulative 5-year recurrence rates of the LDLT group and the DDLT group were similar (14.8% vs 19.0%, p = 0.638), but overall survival in the LDLT group was significantly better than that in the DDLT group (84.2% vs 63.5%, p < 0.0001). Separate multivariate analysis identified different preoperative predictive factors for HCC recurrence (salvage transplantation and Des-gamma-carboxy prothrombin >300 in the LDLT group, beyond Milan criteria in the DDLT group). Combined multivariate analysis of the 2 groups identified recipient's body mass image >30 kg/m(2) as an independent risk factor for overall survival; the technique of transplantation (LDLT or DDLT) was not found to be a risk factor.

Conclusions: When compared between the institutes where LDLT or DDLT were the first treatment choices for unresectable HCC, recurrence rates were comparable. Living donor liver trasplantation is a viable treatment option for unresectable HCC, providing recurrence rates similar to those achieved with DDLT.
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http://dx.doi.org/10.1016/j.jamcollsurg.2014.12.009DOI Listing
March 2015

Massive parallel sequencing uncovers actionable FGFR2-PPHLN1 fusion and ARAF mutations in intrahepatic cholangiocarcinoma.

Nat Commun 2015 Jan 22;6:6087. Epub 2015 Jan 22.

1] Barcelona-Clínic Liver Cancer Group (HCC Translational Research Laboratory, Liver Unit, Hepato-biliary Surgery), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, CIBERehd, Universitat de Barcelona, Barcelona 08036, Spain [2] Mount Sinai Liver Cancer Program (Divisions of Liver Diseases, Department of Medicine, Department of Pathology, Recanati Miller Transplantation Institute), Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York 10029, USA [3] Institució Catalana de Recerca i Estudis Avançats, Barcelona 08010, Spain.

Intrahepatic cholangiocarcinoma (iCCA) is a fatal bile duct cancer with dismal prognosis and limited therapeutic options. By performing RNA- and exome-sequencing analyses, we report a novel fusion event, FGFR2-PPHLN1 (16%), and damaging mutations in the ARAF oncogene (11%). Here we demonstrate that the chromosomal translocation t(10;12)(q26;q12) leading to FGFR2-PPHLN1 fusion possesses transforming and oncogenic activity, which is successfully inhibited by a selective FGFR2 inhibitor in vitro. Among the ARAF mutations, N217I and G322S lead to activation of the pathway and N217I shows oncogenic potential in vitro. Screening of a cohort of 107 iCCA patients reveals that FGFR2 fusions represent the most recurrent targetable alteration (45%, 17/107), while they are rarely present in other primary liver tumours (0/100 of hepatocellular carcinoma (HCC); 1/21 of mixed iCCA-HCC). Taken together, around 70% of iCCA patients harbour at least one actionable molecular alteration (FGFR2 fusions, IDH1/2, ARAF, KRAS, BRAF and FGF19) that is amenable for therapeutic targeting.
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http://dx.doi.org/10.1038/ncomms7087DOI Listing
January 2015

Prognostic significance of lymph node metastases in small intestinal neuroendocrine tumors.

Neuroendocrinology 2015 5;101(1):58-65. Epub 2015 Jan 5.

Division of Gastroenterology, Department of Medicine, Mount Sinai School of Medicine, New York, N.Y., USA.

Background/aims: Current staging guidelines for small intestinal neuroendocrine tumors (SI-NETs) differentiate between the presence (N1) and absence (N0) of lymph node (LN) metastases. However, the prognostic significance of the extent of LN involvement remains unknown. In this study, we used data from a population-based cancer registry to examine whether involvement of a higher number of LNs is associated with worse survival.

Methods: We used the Surveillance, Epidemiology, and End Results (SEER) database to identify patients with histologically confirmed, surgically resected SI-NETS diagnosed between 1988 and 2010. Patients were classified into three groups by the LN ratio (number of positive LNs/number of total LNs examined, LNR): ≤0.2, >0.2-0.5, and >0.5. We used the Kaplan-Meier method and Cox models to assess NET cancer-specific survival differences (up to 10 years from diagnosis) according to LNR status.

Results: We identified 2,984 surgically resected patients with stage IIIb (N1, M0) SI-NETs with detailed LN data. More than half of the NETs were located in the ileum. A higher LNR was significantly associated with worse NET cancer-specific survival (p < 0.0001). Ten-year NET-specific survival was 85, 77, and 74% for patients in the ≤0.2, >0.2-0.5, and >0.5 LNR groups, respectively. In stratified analyses, higher LNR groups had worse survival only in early tumor (T1, T2) disease (p < 0.0001).

Conclusions: The extent of LN involvement provides independent prognostic information on patients with LN-positive SI-NETs. This information may be used to identify patients at high risk of recurrence and inform decisions about the use of adjuvant therapy.
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http://dx.doi.org/10.1159/000371807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4403253PMC
December 2015

Metzenbaum-assisted liver resection: a safe and effective liver resection technique.

Dig Surg 2014 12;31(4-5):312-7. Epub 2014 Nov 12.

Recanati-Miller Transplantation Institute, Mount Sinai School of Medicine, New York, N.Y., USA.

Aim: We hereby present and evaluate a technique for hepatic parenchymal transection based on the application of Metzenbaum scissors and clips during liver ischemia.

Methods: Our technique was retrospectively evaluated in 32 noncirrhotic, noncholestatic patients with intrahepatic cholangiocarcinoma and 32 patients with hepatocellular carcinoma (23 of whom cirrhotic, 71.9%). Patient data were retrieved from our Hepatobiliary Surgery Database. Type and duration of vascular clamping, blood transfusion requirements, marginal status and immediate postoperative complications were analyzed.

Results: Twenty-seven extended (>4 liver segments; 42.2%) and 37 nonextended (≤4 liver segments; 57.8%) liver resections were analyzed. Warm liver ischemia duration was 14 (interquartile range: 11-17.8) min. Thirty-three patients (51.6%) were transfused with a median of 2 (1.5-3) units of packed red blood cells. Tumor-free margins were achieved in 90.6% of cases (n = 58). The overall morbidity rate was 18.8% with a 4.7% mortality rate. Our technique allowed for excellent identification and safe dissection and preservation, or ligation of major liver vessels.

Conclusions: The proposed technique is simple, fast, safe and with low cost. It is associated with limited postoperative complications while from an oncologic standpoint it enables the surgeon to achieve a high percentage of tumor-free margins while protecting major vascular structures.
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http://dx.doi.org/10.1159/000366288DOI Listing
October 2015

Outcomes following resection of intrahepatic cholangiocarcinoma.

HPB (Oxford) 2015 Apr 14;17(4):344-51. Epub 2014 Nov 14.

Department of Surgery, Division of Surgical Oncology, Mount Sinai Medical Center, New York, NY, USA.

Objectives: The aim of this analysis was to examine prognostic features and outcomes in patients undergoing resection for intrahepatic cholangiocarcinoma (ICC).

Methods: A retrospective chart review was performed in all patients who underwent R0 or R1 resection for primary ICC between 1995 and 2011. Clinical data were abstracted and statistical analyses were conducted in the standard fashion.

Results: A total of 82 patients underwent curative hepatectomy for primary ICC; 51 patients in this cohort developed recurrence. The median follow-up of survivors was 27 months (range: 1-116 months). Recurrences were intrahepatic (65%), associated with multiple tumours (54%) and occurred during the first 2 years after hepatectomy (86%). The main factor associated with recurrence after resection was the presence of satellite lesions. Overall 5-year disease-free survival after primary resection was 16%. Factors associated with poor survival were transfusion and perineural invasion. Treatment of recurrence was undertaken in 89% of patients and repeat surgical resection was performed in 15 patients. The 3-year survival rate after recurrence was 25%. Prolonged survival after recurrence was associated with a solitary tumour recurrence.

Conclusions: Despite curative resection of ICC, recurrence can be expected to occur in 79% of patients at 5 years. Predictors of survival and recurrence after resection vary in the literature. In patients with recurrence, selection of the optimal treatment remains challenging.
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http://dx.doi.org/10.1111/hpb.12359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368399PMC
April 2015

Differences in surgical outcomes between hepatitis B- and hepatitis C-related hepatocellular carcinoma: a retrospective analysis of a single North American center.

Ann Surg 2014 Oct;260(4):650-6; discussion 656-8

*Liver Cancer Program, Icahn School of Medicine at Mount Sinai, New York, NY †Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY; and ‡Lenox Hill Hospital, New York, NY.

Objective: Compare surgical outcomes for hepatitis B virus (HBV)-hepatocellular carcinoma (HCC) versus hepatitis C virus (HCV)-hepatocellular carcinoma (HCC).

Background: HCC is the second leading cause of death from cancer worldwide and is associated with hepatitis virus infection in 80% of cases.

Methods: Between 1997 and 2011, 1008 patients with hepatitis B (HBV, n = 431) or hepatitis C (HCV, n = 577) underwent resection (n = 567) or transplantation (n = 441). Resection was indicated for Child's A patients with single HCC; transplantation was indicated for patients within Milan criteria. Univariate and multivariate analyses were performed as well as survival and recurrence analysis using log-rank test.

Results: Based on uniform application of these criteria, resection: transplantation ratio was 3.6 for patients with HBV and 0.67 for patients with HCV. Resection: Patients with HBV had larger tumors and higher α-fetoprotein but less satellites and macrovascular invasion; 68% of HBV versus 89% of HCV were cirrhotic. Survival was better (P < 0.001) and recurrence was lower (P = 0.009) for HBV. Independent predictors of death included HCV (P = 0.024), transfusion (P = 0.013), and HCC of greater than 5 cm (P = 0.013). Limiting analysis to patients with cirrhosis, survival with HBV remained superior (P = 0.020) but recurrence did not. Transplantation: Tumors were similar in HBV and HCV. Survival was better (P = 0.002) for HBV; recurrence was similar. Independent predictors of death were HCV (P < 0.001), poor differentiation (P = 0.049), vascular invasion (P = 0.002), and outside Milan (P = 0.032). Limiting analysis to patients within Milan, HBV survival remained better for both resection (P = 0.030) and transplantation (P = 0.002).

Conclusions: Survival after both resection and transplantation for HCC was better in HBV- than in HCV-related HCC whereas recurrence was also lower for HBV-HCC in the resection group, these differences are influenced by both liver and tumor factors.
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http://dx.doi.org/10.1097/SLA.0000000000000917DOI Listing
October 2014

Surgical treatment of intrahepatic cholangiocarcinoma in the USA.

J Hepatobiliary Pancreat Sci 2015 Feb 4;22(2):124-30. Epub 2014 Sep 4.

Recanati/Miller Transplantation Institute, Mount Sinai Medical Center, 1 Gustave Levy Place, Box 1104, New York, NY, 10029, USA.

Cholangiocarcinoma (CC) is a malignancy that arises from the epithelial cells of the biliary system (ductules as well as large ducts, and likely from progenitor cells, as well). Intrahepatic CC (ICC) is the second most common primary hepatic malignancy after hepatocellular carcinoma (HCC), and accounts for 10-15% of primary liver cancers. ICC differs from both extrahepatic and CC and HCC and has unique risk factors, histological features, genetic alterations and clinical outcomes. The natural history and results of surgical intervention are not well described as ICC is a relatively uncommon tumor, especially in the USA. This article reviews the literature relevant to the surgical management and outcome of patients with ICC in the USA.
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http://dx.doi.org/10.1002/jhbp.157DOI Listing
February 2015

Current management of hepatocellular carcinoma.

World J Gastroenterol 2014 Aug;20(30):10223-37

Parissa Tabrizian, Sasan Roayaie, Myron E Schwartz, Mount Sinai Liver Cancer Program, Mount Sinai Medical Center, New York, NY 10029, United States.

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and leading cause of death among patients with cirrhosis. Treatment guidelines are based according to the Barcelona Clinic Liver Cancer staging system. The choice among therapeutic options that include liver resection, liver transplantation, locoregional, and systemic treatments must be individualized for each patient. The aim of this paper is to review the outcomes that can be achieved in the treatment of HCC with the heterogeneous therapeutic options currently available in clinical practice.
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http://dx.doi.org/10.3748/wjg.v20.i30.10223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4130831PMC
August 2014

Ischemia time impacts recurrence of hepatocellular carcinoma after liver transplantation.

Hepatology 2015 Mar 30;61(3):895-904. Epub 2015 Jan 30.

Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY; Division of Transplant and Hepatobiliary Surgery, Henry Ford Transplant Institute, Henry Ford Hospital, Detroit, MI.

Unlabelled: Although experimental evidence has indicated that ischemia-reperfusion (I/R) injury of the liver stimulates growth of micrometastases and adhesion of tumor cells, the clinical impact of I/R injury on recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) has not been fully investigated. To study this issue, we conducted a retrospective review of the medical records of 391 patients from two transplant centers who underwent LT for HCC. Ischemia times along with other tumor/recipient variables were analyzed as risk factors for recurrence of HCC. Subgroup analysis focused on patients with HCC who had pathologically proven vascular invasion (VI) because of the associated increased risk of micrometastasis. Recurrence occurred in 60 patients (15.3%) with median time to recurrence of 0.9 years (range, 40 days-4.6 years). Cumulative recurrence curves according to cold ischemia time (CIT) at 2-hour intervals and warm ischemia time (WIT) at 10-minute intervals showed that CIT>10 hours and WIT>50 minutes were associated with significantly increased recurrence (P=0.015 and 0.036, respectively). Multivariate Cox's regression analysis identified prolonged cold (>10 hours; P=0.03; hazard ratio [HR]=1.9) and warm (>50 minutes; P=0.003; HR=2.84) ischemia times as independent risk factors for HCC recurrence, along with tumor factors, including poor differentiation, micro- and macrovacular invasion, exceeding Milan criteria, and alpha-fetoprotein>200 ng/mL. Prolonged CIT (P=0.04; HR=2.24) and WIT (P=0.001; HR=5.1) were also significantly associated with early (within 1 year) recurrence. In the subgroup analysis, prolonged CIT (P=0.01; HR=2.6) and WIT (P=0.01; HR=3.23) were independent risk factors for recurrence in patients with VI, whereas there was no association between ischemia times and HCC recurrence in patients with no VI.

Conclusion: Reducing ischemia time may be a useful strategy to decrease HCC recurrence after LT, especially in those with other risk factors.
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http://dx.doi.org/10.1002/hep.27358DOI Listing
March 2015

Actual 10-year survival following hepatectomy for hepatocellular carcinoma.

HPB (Oxford) 2014 Sep 24;16(9):830-5. Epub 2013 Dec 24.

Mount Sinai Liver Cancer Programme, Mount Sinai School of Medicine, New York, NY, USA.

Objectives: This study was conducted to compare 10-year survivors with patients who survived <10 years in a large Western series of patients submitted to hepatectomy for hepatocellular carcinoma (HCC).

Methods: A retrospective review of a series of hepatic resections conducted in a referral centre for HCC between January 1987 and October 2002 was conducted.

Results: A total of 176 patients were analysed. Twenty-eight patients survived ≥ 10 years (Group A) and were compared with the 148 patients who did not (Group B). Group A had smaller tumours (5.7 cm versus 8.2 cm; P = 0.001) and a lower incidence of microvascular invasion (18.5% versus 37.1%; P = 0.004). Recurrence did not differ significantly (Group A 18/28, 64.3% versus Group B 94/148, 63.5%). Median time to recurrence was longer in Group A (70 months versus 15 months; P < 0.0001), and more patients in Group A were able to undergo curative treatment for recurrence (88.8% versus 40.4%; P < 0.0001). Multivariate analysis showed that lack of vascular invasion (P = 0.020), absence of perioperative transfusion (P = 0.014), and recurrence at >2 years after primary resection (P = 0.045) were significantly associated with 10-year survival.

Conclusions: Ten-year survival after liver resection for HCC can be expected in approximately 15% of patients. Recurrence does not preclude longterm survival. Recurrence at >2 years after resection, absence of vascular invasion, and absence of perioperative transfusion are independently associated with 10-year survival.
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http://dx.doi.org/10.1111/hpb.12206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159456PMC
September 2014
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