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Anatomical liver segmentectomy 2 for combined hepatocellular carcinoma and cholangiocarcinoma with tumor thrombus in segment 2 portal branch
Hiromichi Ishii, Takuma Kobayashi, Michihiro Kudou, Masumi Nishimura, Atsushi Toma, Kenji Nakamura, Takeshi Mazaki, Tsuyoshi Itoh
World Journal of Surgical Oncology , 2012, DOI: 10.1186/1477-7819-10-22
Abstract: A 52-year-old man was preoperatively diagnosed with hepatocellular carcinoma in segment 2 with tumor thrombus in the segment 2 portal branch. Anatomical liver segmentectomy 2, including separation of the hepatic arteries, portal veins, and bile duct, enabled us to remove the tumor and portal thrombus completely. Modified selective hepatic vascular exclusion, which combines extrahepatic control of the left and middle hepatic veins with occlusion of left hemihepatic inflow, was used to reduce blood loss. A pathological examination revealed combined hepatocellular carcinoma and cholangiocarcinoma with tumor thrombus in the segment 2 portal branch. No postoperative liver failure occurred, and remnant liver function was adequate.The separation method of the hepatic arteries, portal veins, and bile duct is safe and feasible for a liver cancer patient with portal vein tumor thrombus. Modified selective hepatic vascular exclusion was useful to control bleeding during liver transection. Anatomical liver segmentectomy 2 using these procedures should be considered for a patient with a liver tumor located at segment 2 arising from a damaged liver.Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is an uncommon primary liver cancer subtype [1] and is difficult to correctly diagnose preoperatively. Most patients with cHCC-CC are preoperatively misdiagnosed with hepatocellular carcinoma (HCC) or cholangiocarcinoma (CC) including our present patient. Hepatic resection leads to improved survival in patients with cHCC-CC [2-5] or HCC with portal vein tumor thrombus (PVTT) [6,7]. In patients with liver cirrhosis, extended liver resection for liver cancer is sometimes not feasible because of decreased liver functional reserve; therefore, anatomical segmentectomy or limited non-anatomical hepatectomy must be performed. We herein report an anatomical liver segmentectomy 2 surgical procedure successfully performed for a patient with cHCC-CC and PVTT in the segment 2 porta
Prognosis of hepatocellular carcinoma expressing cytokeratin 19: Comparison with other liver cancers  [cached]
Jung Il Lee,Jin-Woo Lee,Joon Mee Kim,Ja Kyung Kim
World Journal of Gastroenterology , 2012, DOI: 10.3748/wjg.v18.i34.4751
Abstract: AIM: To investigate whether expressing biliary phenotype predicted poor outcome after the surgical treatment in primary liver cancers. METHODS: Out of 204 patients that underwent liver resection due to hepatocellular carcinoma (HCC), liver specimens of 70 patients with HCC were evaluated for biliary components by cytokeratin (CK) 19 immunostain (CK19- HCC and CK19+ HCC). CK19 positivity was defined as membranous and/or cytoplasmic expression in ≥ 5% of tumor cells with moderate or strong intensity. Patients with other primary liver cancers, such as combined HCC and cholangiocarcinoma (cHCC-CC), intrahepatic cholangiocarcinoma (ICC) who received curative liver resection, were also included in the study. Clinical characteristics of CK19- HCC and CK19+ HCC patients, including survival outcome after curative liver resection, were compared with that of cHCC-CC and ICC patients. RESULTS: The overall survival (OS) rate of CK19- HCC (n = 49) after the curative surgical treatment was 90.7%, and 80.4% at 1 and 5 years after the resection. OS rate of CK19+ HCC (n = 21) was 74.3%, 28.9% and OS rate of cHCC-CC (n = 22) was 66.7%, 32.2% at 1 and 5 years after the surgery. For ICC (n = 19), 1 and 5-year-OS rate was 50.2% and 14.3% after the curative resection. The OS rates of CK19+ HCC and cHCC-CC were significantly lower than that of CK19- HCC, but higher than the OS rate of ICC (P = 0.000). There was no statistically significant difference in OS rate between CK19+ HCC and cHCC-CC. The disease free survival (DFS) rate of CK19- HCC was 72.0% and 54.5% at 1 and 3 years after the surgical treatment. DFS rate of CK19+ HCC was 53.3%, 34.3% and DFS rate of cHCC-CC was 51.5%, 39.2% at 1 and 3 years after the resection. For ICC, 1 and 3-year-DFS rate was 28.0% and 14.0% after the curative resection. DFS rate of CK19- HCC was significantly higher than that of ICC (P = 0.017), but marginally higher than DFS rate of either CK19+ HCC or cHCC-CC (P = 0.097, P = 0.089, respectively). Predictors of outcome after the surgery of primary liver cancer were pathology of the resected mass, existence of microvascular invasion and accompanying satellite nodule. CONCLUSION: Primary liver cancers with biliary components tended to show poorer surgical outcome. This suggested that immuno-phenotype of liver cancers was as important as their morphological classification.
Combined Hepatocellular-Cholangiocarcinoma with Stem Cell Features—Case Report  [PDF]
Leonardo Verza, Carlos Henrique Rosas, Gabriel Marques Neves, Tércia Neves, Maria Dirlei Begnami, Marcos Duarte Guimar?es
Case Reports in Clinical Medicine (CRCM) , 2018, DOI: 10.4236/crcm.2018.710046
Abstract: Combined hepatocholangiocarcinoma is a rare and unique form of primary hepatic neoplasm, expressing histopathological and phenotypic aspects of hepatocellularcarcinoma and cholangiocarcinoma in the same tumor. Diagnosis may be performed by imaging, showing typical features of both components. We present a case of a 55-year-old woman presenting with abdominal pain and a hepatic mass. The patient underwent surgery and combined hepatocholangiocarcinoma with stem cells features was confirmed on pathological analysis. There are no signs of recurrence to date. Combined hepatocholangiocarcinoma requires a preoperative diagnosis, since it is a unique entity with higher rates of local and lymph node recurrence, compared to isolated forms.
Increased Expression of Yes-Associated Protein 1 in Hepatocellular Carcinoma with Stemness and Combined Hepatocellular-Cholangiocarcinoma  [PDF]
Gi Jeong Kim, Hyunki Kim, Young Nyun Park
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0075449
Abstract: Combined hepatocellular-cholangiocarcinoma (cHC-CC) and some hepatocellular carcinomas (HCCs) express stemness-related markers, such as epithelial adhesion molecule (EpCAM) and keratin 19 (K19), the expression of which has been reported to be associated with more aggressive behavior therein than in HCCs without. Yes-associated protein 1 (YAP1), a potential oncogene, is known to promote stem cell proliferation. In the present study, YAP1 expression and clinicopathological features were evaluated and compared among three groups comprising 36 HCCs that expressed both EpCAM and K19, 64 HCCs that did not express EpCAM and K19, and 58 cHC-CCs, which consisted of 38 cases of the classical type and 20 cases of the intermediate-cell subtype. YAP1 expression was more frequently noted in EpCAM(+)/K19(+) HCCs (55.6%) and in cHC-CCs (67.2%) than in EpCAM(?)/K19(?) HCCs (17.2%) (P<0.001 for both). In cHC-CCs, YAP1 expression was observed in 63% of classical type cHC-CCs and in 75% of the intermediate subtype; moreover, such expression was correlated with poorer histological differentiation (P = 0.017) and was more frequently noted in transition zones than in HCC areas (P = 0.060). Disease-free and overall survival showed a statistically significant difference among the three groups: disease-free survival was highest for EpCAM(?)/K19(?) HCCs and lowest for cHC-CCs, with EpCAM(+)/K19(+) HCCs falling in between (P<0.05). Overall survival rate was lower in HCCs and cHC-CCs with YAP1 expression compared to those without (P = 0.05), whereas disease-free survival showed no significant difference according to YAP1 expression. Increased YAP1 expression was more frequently found in cHC-CCs and HCCs with stemness than in HCCs without, and a YAP1 pathway is suggested to be involved in the obtainment stemness characteristics in HCCs and cHC-CCs.
Addition of hepatectomy decreases liver recurrence and leads to long survival in hilar cholangiocarcinoma
Zheng Shi, Ming-Zhi Yang, Qing-Liang He, Rong-Wen Ou, You-Ting Chen
World Journal of Gastroenterology , 2009,
Abstract: AIM: To evaluate hepatic recurrence and prognostic factors for survival in patients with surgically resected hilar cholangiocarcinoma in a single institution over the last 13 years.METHODS: From 1994 to 2007, all patients with hilar cholangiocarcinoma referred to a surgical clinic were evaluated. Demographic data, tumor characteristics, and outcome were analyzed retrospectively. Outcome was compared in patients who underwent additional liver resection with resection of the tumor.RESULTS: Of the 69 patients submitted to laparotomy for tumor resection, curative resection (R0 resection) was performed in 40 patients, and palliative resection in 29. Thirty-one patients had only duct resection, and 38 patients had combined duct resection with liver resection including 34 total or part caudate lobes. Curative rates with the combined hepatectomy were significantly improved compared with those without additional hepatectomy (27/38 vs 13/31; χ2 = 5.94, P < 0.05). Concomitant liver resection was associated with a decreased incidence of initial recurrence in liver one year after surgery (11/38 vs 23/31; χ2 = 13.98, P < 0.01). The 3-year survival rate after R0 resection was 30.7% and was 10.5% for palliative resection. R0 resection improved the 3-year survival rate (30.7% vs 10.5%; χ2 = 12.47, P < 0.01).CONCLUSION: Hepatectomy, especially including the caudate lobe combined with bile duct resection should be considered standard treatment to cure hilar cholangiocarcinoma.
Proteomic Studies of Cholangiocarcinoma and Hepatocellular Carcinoma Cell Secretomes
Chantragan Srisomsap,Phannee Sawangareetrakul,Pantipa Subhasitanont,Daranee Chokchaichamnankit,Khajeelak Chiablaem,Vaharabhongsa Bhudhisawasdi,Sopit Wongkham,Jisnuson Svasti
Journal of Biomedicine and Biotechnology , 2010, DOI: 10.1155/2010/437143
Abstract: Cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC) occur with relatively high incidence in Thailand. The secretome, proteins secreted from cancer cells, are potentially useful as biomarkers of the diseases. Proteomic analysis was performed on the secreted proteins of cholangiocarcinoma (HuCCA-1) and hepatocellular carcinoma (HCC-S102, HepG2, SK-Hep-1, and Alexander) cell lines. The secretomes of the five cancer cell lines were analyzed by SDS-PAGE combined with LC/MS/MS. Sixty-eight proteins were found to be expressed only in HuCCA-1. Examples include neutrophil gelatinase-associated lipocalin (lipocalin 2), laminin 5 beta 3, cathepsin D precursor, desmoplakin, annexin IV variant, and annexin A5. Immunoblotting was used to confirm the presence of lipocalin 2 in conditioned media and cell lysate of 5 cell lines. The results showed that lipocalin 2 was a secreted protein which is expressed only in the conditioned media of the cholangiocarcinoma cell line. Study of lipocalin 2 expression in different types of cancer and normal tissues from cholangiocarcinoma patients showed that lipocalin 2 was expressed only in the cancer tissues. We suggest that lipocalin 2 may be a potential biomarker for cholangiocarcinoma.
Major liver resection for hepatocellular carcinoma in the morbidly obese: A proposed strategy to improve outcome
Omar Barakat, Mark D Skolkin, Barry D Toombs, John H Fischer, Claire F Ozaki, R Patrick Wood
World Journal of Surgical Oncology , 2008, DOI: 10.1186/1477-7819-6-100
Abstract: We describe the management of a large hepatocellular carcinoma in a morbidly obese patient (body mass index >50 kg/m2). Additionally, we propose a strategy for reducing postoperative complications and improving outcome after major liver resection.To our knowledge, this is the first report of major liver resection in a morbidly obese patient with hepatocellular carcinoma. The approach we used could make this operation nearly as safe in obese patients as it is in their normal-weight counterparts.Obesity is perhaps the most significant public health problem facing the United States and the Western world today. Each year, an estimated 300,000 Americans die from obesity-related illnesses [1]. The latest National Health and Nutrition Examination data show that the prevalence of obesity with body mass index (BMI) ≥ 30 kg/m2 has increased from 22.9% in 1994 to 30.5% in 2000. The prevalence of morbid obesity (BMI ≥ 40 kg/m2) also significantly increased, from 2.9% to 4.7% [2]. This increase has affected most surgical practices, as surgeons are operating on obese patients in increasing numbers [3,4].Perioperative morbidity, mortality, and prolonged hospital stays are particularly common in obese patients, because these patients often have preexisting cardiac and respiratory disease [3,5]. Moreover, epidemiologic studies have shown that obesity and diabetes are frequently associated with nonalcoholic fatty liver disease, which includes a spectrum of liver disorders that may progress to hepatocellular carcinoma (HCC) [6,7]. Although several studies have analyzed the impact of obesity on patients after major surgical procedures, including liver transplantation [4,8,9], there are, to our knowledge, no data on the outcome of major liver resection for HCC in morbidly obese patients.In this report, we discuss the treatment of a large HCC in a morbidly obese patient with a BMI greater than 50 kg/m2. We also discuss the current literature on surgical complications in obese patients, a
Recent advances of miRNA involvement in hepatocellular carcinoma and cholangiocarcinoma  [PDF]
Kwang Suk Ko, Hui Peng, Hua Tang, Michele E. Cho, Jian Peng, Maria-Angeles Aller, Heping Yang
Open Journal of Internal Medicine (OJIM) , 2012, DOI: 10.4236/ojim.2012.23024
Abstract: MicroRNAs (miRNAs), which are a class of highly evolutionarily conserved non-coding RNAs, modulate gene expression and are regulated by specific genes. Several studies have shown that the expression of miRNAs is deregulated in Hepatitis C virus (HCV) & Hepatitis B virus (HBV) infection, liver cancer progression, tumor invasion and metastasis. There are a number of high-quality review articles relative to the general role of miRNA alterations in carcinogenesis and specific reviews dealing with the miRNA changes in hepatocellular carcinoma (HCC) and cholangio-carcinoma (CCA). Since primary liver cancer is predominantly comprised of HCC and intrahepatic cholangiocarcinoma (ICC), in the present review we specifically focus on recent advances of miRNAs related to tumorigenesis, invasion and metastasis of primary liver cancer, with special emphasis on their relationships to their target genes. HCV & HBV are major causes of liver disease, including acute and chronic hepatitis, liver cirrhosis, and HCC, while HCV infection is a risk factor for ICC. We also discuss the mi-RNA alterations involved in HCV & HBV infection. We briefly describe advances in molecular signaling of miRNAs in liver cancers and present insights into new therapeutic clues that target liver cancer.
Prospective, randomized, double-blind, multi-center, Phase III clinical study on transarterial chemoembolization (TACE) combined with Sorafenib? versus TACE plus placebo in patients with hepatocellular cancer before liver transplantation – HeiLivCa [ISRCTN24081794]
K Hoffmann, H Glimm, B Radeleff, G Richter, C Heining, I Schenkel, A Zahlten-Hinguranage, P Schirrmacher, J Schmidt, MW Büchler, D Jaeger, C von Kalle, P Schemmer
BMC Cancer , 2008, DOI: 10.1186/1471-2407-8-349
Abstract: The HeiLivCa study is a double-blinded, controlled, prospective, randomized multi-centre phase III trial. Patients in study arm A will be treated with transarterial chemoembolization plus sorafenib 400 mg bid. Patients in study arm B will be treated with transarterial chemoembolization plus placebo. A total of 208 patients with histologically confirmed hepatocellular carcinoma or HCC diagnosed according to EASL criteria will be enrolled. An interim patients' analysis will be performed after 60 events. Evaluation of time-to-progression as primary endpoint (TTP) will be performed at 120 events. Secondary endpoints are number of patients reaching LTx, disease control rates, OS, progression free survival, quality of live, toxicity and safety.As TACE is the most widely used primary treatment of HCC before LTx and sorafenib is the only proven effective systemic treatment for advanced HCC there is a strong rational to combine both treatment modalities. This study is designed to reveal potential superiority of the combined TACE plus sorafenib treatment over TACE alone and explore a new neo-adjuvant treatment concept in HCC before LTx.Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide with more than 1 million deaths annually [1]. The prevalence of Hepatitis B and C with consecutive liver cirrhosis and HCC tumor growth leads to an increasing incidence of HCC especially in Europe and the USA [2]. HCC develops in a cirrhotic liver in 80% of cases, with an annual incidence of 2–6% for hepatitis B virus carriers and 3–5% for hepatitis C virus infected individuals. Two decades ago, the prognosis of HCC was devastating with most patients dying within the first year after diagnosis irrespective of their treatment [3]. The development of standardized surveillance strategies and the introduction of the Barcelona-clinic liver cancer classification (BCLC) for clinical management of HCC have significantly improved outcome. In industrialized countries 30–40% of patie
Fine needle aspiration biopsy of the liver: Algorithmic approach and current issues in the diagnosis of hepatocellular carcinoma
Wee Aileen
CytoJournal , 2005,
Abstract: The role of fine needle aspiration biopsy (FNAB) in the evaluation of focal liver lesions has evolved. Guided FNAB is still useful to procure a tissue diagnosis if clinical, biochemical and radiologic findings are inconclusive. Major diagnostic issues include: (i) Distinction of benign hepatocellular nodular lesions from reactive hepatocytes, (ii) Distinction of well-differentiated hepatocellular carcinoma (WD-HCC) from benign hepatocellular nodular lesions, (iii) Distinction of poorly differentiated HCC from cholangiocarcinoma and metastatic carcinomas, (iv) Determination of histogenesis of malignant tumor, and (v) Determination of primary site of origin of malignant tumor. This review gives a general overview of hepatic FNAB; outlines an algorithmic approach to cytodiagnosis with emphasis on HCC, its variants and their mimics; and addresses current diagnostic issues. Close radiologic surveillance of high-risk cirrhotic patients has resulted in the increasing detection of smaller lesions with many subjected to biopsy for tissue characterization. The need for tissue confirmation in clinically obvious HCC is questioned due to risk of malignant seeding. When a biopsy is indicated, core needle biopsy is favored over FNAB. The inherent difficulty of distinguishing small/early HCC from benign hepatocellular nodular lesions has resulted in indeterminate reports. Changing concepts in the understanding of the biological behavior and morphologic evolution of HCC and its precursors; and the current lack of agreement on the morphologic criteria for distinguishing high-grade dysplastic lesions (with small cell change) from WD-HCC, have profound impact on nomenclature, cytohistologic interpretation and management. Optimization of hepatic FNAB to enhance the yield and accuracy of diagnoses requires close clinicopathologic correlation; combined cytohistologic approach; judicious use of ancillary tests; and skilled healthcare teams.
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