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ABSTRACT: BACKGROUND: Metastatic tumor antigen 1 (MTA1) overexpression is closely associated with postoperative recurrence of hepatocellular carcinoma (HCC). It has been suggested that pegylated interferon (Peg-IFN) can prevent the occurrence of HCC in patients who have chronic viral hepatitis. In this study, the authors examined whether postoperative adjuvant Peg-IFN therapy can reduce the recurrence of MTA1-positive HCC after curative surgical resection. METHODS: In this case-control study, 93 patients with MTA1-positive HCC who underwent curative surgical resection were prospectively enrolled. The median patient age was 53 years (range, 27-78); there were 65 men and 28 women; the etiology was hepatitis B virus (HBV) in 77 patients, hepatitis C virus (HCV) in 6 patients, and non-HBV/non-HCV in 10 patients; 31 patients received Peg-IFN (Peg-INTRON(®) ) subcutaneously at a dose of 50 μg per week for 12 months (the Peg-IFN group); and the remaining 62 patients were followed only and did not receive any adjuvant therapies (control group). Patients were followed every 1 to 3 months for a median of 24 months. RESULTS: HCC recurred postoperatively in 26 of 93 patients (28%), and 9 patients (10%) died during follow-up. The overall cumulative recurrence rates were significantly lower in the Peg-IFN group than in the control group (7% and 14% vs 24% and 34% at 1 year and 2 years, respectively; P < .05). In addition, the 1-year and 2-year cumulative survival rates were higher in the Peg-IFN group compared with the control group (100% vs 93% and 100% vs 87%, respectively; P < .05). In multivariate analysis, the receipt of adjuvant Peg-IFN therapy, in addition to having a lower Cancer of the Liver Italian Program score and being a woman, was an independent, favorable factor for a lower risk of postoperative recurrence. CONCLUSIONS: The current data indicate that adjuvant Peg-IFN therapy may reduce the recurrence of HCC in patients who have MTA1-positive HCC after curative surgical resection. Cancer 2013. © 2013 American Cancer Society.
Cancer 04/2013; · 4.77 Impact Factor
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ABSTRACT: Small intestinal adenocarcinomas (SIACs) are rare, and their molecular pathogenesis is largely unknown. To define the roles of E-cadherin and β-catenin, we performed immunohistochemistry for E-cadherin and β-catenin in 194 surgically resected SIACs with tissue microarrays and compared the data with clinicopathologic factors, including survival rates of patients with SIAC. Loss of E-cadherin expression and aberrant β-catenin expression were observed in 41.8% (81/194 cases) and 40.7% (79/194 cases) of SIACs, respectively. Combined loss of E-cadherin and aberrant β-catenin expression was observed in 24.2% (47/194 cases) of SIACs, and this feature was most frequently observed in mucinous adenocarcinomas and signet ring cell carcinomas (P < .001), poorly differentiated and undifferentiated carcinomas (P < .001), and tumors with advanced pT classification (P = .03). Survival times for patients with SIAC with both loss of E-cadherin and aberrant β-catenin expression (median, 13.9 months) were significantly shorter than those for patients without aberrant expression of both proteins (49.9 months), as determined by univariate (P < .001) and multivariate (P = .01) analyses. In conclusion, loss of E-cadherin and aberrant β-catenin expression correlate with poorly differentiated tumors, advanced T classification, and decreased patient survival time; therefore, it could be a prognostic factor in patients with SIAC.
American Journal of Clinical Pathology 02/2013; 139(2):167-76. · 2.60 Impact Factor
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ABSTRACT: We summarize our experience in the pathological diagnosis of late complications of liver transplantation (LT) to better understand the causes of late allograft dysfunction in a population mostly composed of patients with hepatitis B virus (HBV) infection.
We reviewed 361 post-transplant liver biopsies from 174 patients who underwent LT and first presented with liver function abnormalities 3 months post-procedure. The underlying diseases included HBV-associated liver disease (77%), toxic or alcoholic liver disease (10.3%), hepatitis C virus (HCV)-associated liver disease (8.6%), primary biliary cirrhosis (1.2%), primary sclerosing cholangitis (1.2%), and metabolic disease (1.7%).
The three most common late complications were acute rejection (32.5%), recurrent disease (19.1%), and biliary complication (17.1%). Patients who underwent LT for HBV infection or for drug- or alcohol-related liver disease had a lower incidence of recurring disease than those who underwent transplantation for HCV infection. During post-transplantation months 3-12, acute rejection was the most common cause of allograft dysfunction and recurring disease was the leading cause for allograft dysfunction (p=0.039). The two primary causes of late allograft dysfunction have overlapping histological features, although acute rejection more frequently showed bile duct damage and vascular endothelialitis than recurring HBV infection, and recurring HBV infection had more frequent lobular activity and piecemeal necrosis.
The causes of late liver allograft dysfunction are closely associated with the original liver diseases and the period after LT. Careful attention is required for differential diagnosis between acute rejection and recurrent HBV.
The Korean Journal of Pathology 02/2013; 47(1):21-27. · 0.16 Impact Factor
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ABSTRACT: PURPOSE: To determine the usefulness of enhancement by iodized oil deposits on computed tomography (CT) following transarterial chemoembolization for hepatocellular carcinoma (HCC), and to compare the reliability of such CT imaging with that of magnetic resonance (MR) imaging. MATERIALS AND METHODS: Fifty-one patients for whom resected or explanted livers containing chemoembolized HCC lesions of at least 1 cm were available. Imaging responses were determined based on modified Response Evaluation Criteria In Solid Tumors (mRECIST) and European Association for the Study of the Liver (EASL) criteria for 59 target tumors on CT and MR scans before surgery. CT-based evaluation was performed per mRECIST and EASL criteria, considering iodized oil retention as indicating necrosis and, alternatively, as enhancing viable tissue ("mRECIST-Lipiodol" and "EASL-Lipiodol"). Pathologic necrosis was graded as 100%, 50%-99%, or less than 50%. RESULTS: Goodman-Kruskal γ-values for radiologic-pathologic correlation were greater than 0.95 for mRECIST and EASL criteria on CT or MR imaging. However, mRECIST-Lipiodol and EASL-Lipiodol measurements showed weaker correlation with pathologic findings, with γ-values of 0.797 and 0.846, respectively. With respect to intermethod agreement, weighted γ-values for mRECIST by CT and MR, and for EASL criteria by CT and MR, both exceeded 0.80, whereas mRECIST-Lipiodol and EASL-Lipiodol showed only moderate levels of agreement with mRECIST/EASL criteria by CT or MR imaging, with γ-values of 0.522-0.631. CONCLUSIONS: Response estimation based on measurement of iodized oil deposits as necrosis on CT when applying enhancement criteria after chemoembolization for HCC correlated well with actual pathologic class, and agreed with MR-based evaluation.
Journal of vascular and interventional radiology: JVIR 01/2013; · 1.81 Impact Factor
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ABSTRACT: OBJECTIVES: We retrospectively investigated the prognostic value of hepatocyte nuclear factor-1 (HNF1) proteins in 159 liver transplant patients with hepatocellular carcinomas (HCC), including 36 (22.6%) exceeding the Milan criteria. METHODS: Expression of alpha-fetoprotein (AFP), HNF1α, and HNF1β was examined by immunohistochemistry on duplicate tissue microarray slides containing the HCC tumor explants. Times to recurrence and cancer death were analyzed based on the Cox regression model and compared according to expression of markers of interest. We compared risk predictions using area under the receiver operator curves (AU-ROCs) and c statistics. RESULTS: AFP, HNF1α, and HNF1β were positive in 22.6%, 46.5%, and 61%, respectively, of the tumor immunoprofiles. Although several variables were associated with times to recurrence and cancer death in univariate Cox analyses, only AFP expression for time to recurrence, and the Milan criteria and HNF1β expression for times to recurrence and cancer death, remained significant after multivariate adjustment. Expression of HNF1β, but not of HNF1α, was related to serum AFP ≥200 ng/mL, microvascular invasion, and AFP expression (p<0.05). A subgroup analysis showed that in the within-Milan group, recurrence and cancer death rates at 10 years in the HNF1β-negative patients were approximately one-tenth of those in the HNF1β-positive patients, but the difference was not significant in the non-Milan group. Addition of HNF1β expression to the Milan criteria increased the c statistics and AU-ROCs for both recurrence and mortality (p<0.05). CONCLUSIONS: Immunohistological detection of HNF1β predicts recurrence and death specific for HCC post-transplant, and provides an additive benefit over the Milan selection criteria on their own. © 2012 American Association for the Study of Liver Diseases.
Liver Transplantation 12/2012; · 3.39 Impact Factor
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Priya Mathews,
Danbi Lee,
Young-Hwa Chung,
Jeong A Kim,
Ju-Ho Lee,
Young-Joo Jin,
Wonhyung Park,
Heather Lyu,
Elizabeth Jaffee,
Lei Zheng, Eunsil Yu,
Young Joo Lee
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ABSTRACT: PURPOSE: To determine whether the genomic changes in hepatitis B virus (HBV) affect the clinical outcomes of hepatocellular carcinoma (HCC) in patients with HBV-associated HCC treated with curative surgical resection. METHODS: A total of 247 patients with HBV-associated HCC were treated with curative surgical resection. They were followed regularly for a median of 30 months. The whole X, S, basal core promoter (BCP), and precore regions of HBV were sequenced. RESULTS: The genomic changes such as the G1896A at precore, the A1762T/G1764A at BCP, the C1653T and the T1753V at X gene, and pre-S2 deletion were not significantly associated with postoperative recurrence of HCC or survival of patients after curative resection. However, in univariate analysis, younger age, elevated serum α-fetoprotein level, elevated serum alanine aminotransferase level, larger tumor size, microvascular invasion, and advanced Cancer of the Liver Italian Program stage were closely associated with shorter survival after surgical resection. In multivariate analysis, only microvascular invasion revealed to be an independent risk factor of postoperative recurrence (relative risk [RR] 5.406; P < 0.001); the independent risk factors of shorter survival appeared to be infiltrative type (RR 5.110; P = 0.032), larger tumor size (RR 1.976; P = 0.047), and microvascular invasion (RR 6.118; P < 0.001). CONCLUSIONS: The postoperative recurrence or survival period may not be affected by the genomic changes at the precore, BCP, X, and pre-S2 regions in HBV of genotype C2 in patients with HBV-associated HCC treated with curative surgical resection. Rather, it may be closely associated with tumor characteristics, such as the size and type of HCC or presence of microvascular invasion.
Annals of Surgical Oncology 10/2012; · 4.17 Impact Factor
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ABSTRACT: Objectives: Small intestinal adenocarcinoma (SIAC) is an exceedingly rare human malignant tumor, and its association with the S100A14 gene is not known yet. We aimed to investigate the clinicopathological correlations between S100A14 expression and SIAC. Methods: Immunohistochemical analyses of S100A14, p21 and p53 were performed using tissue microarray analysis of 175 surgically resected SIACs. Results: Of 175 SIACs, loss of S100A14 expression was observed in 128 cases (73.1%). Loss of S100A14 expression was associated with lymph node metastasis (p = 0.009) and advanced disease stage (p = 0.013), and was more frequently observed in distal than duodenal tumors (p = 0.043). The majority of SIACs lost p21 expression (93.7%), and significant loss of p21 expression was observed in cancers with high pT stages (pT(3) and pT(4); p = 0.011), lymph node metastasis (p = 0.029) and advanced cancer stage defined by the American Joint Committee on Cancer (p = 0.005). Overexpression of p53 was found in 23.4% of cases. Positive expression of p53 was associated with distally located SIACs (jejunum or ileum; p = 0.006). There was no association between the expression of S100A14 and p21 or p53. Conclusion: Loss of S100A14 in SIAC is common and is associated with higher metastatic potential and advanced clinical stage.
Pathobiology 10/2012; 80(2):95-101. · 1.18 Impact Factor
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ABSTRACT: Members of the HER (ERBB) receptor protein tyrosine kinase family play an important role in regulating cellular division, proliferation, differentiation, and migration and have prognostic significance in a number of cancers. Here, we sought to define their role in extrahepatic cholangiocarcinoma (EHCC). HER2 and HER3 protein expression was studied in 230 EHCC cases using a tissue microarray and compared with clinicopathological variables, including the survival of EHCC patients. HER3 was predominantly localized to the cytoplasm, whereas HER2 exhibited a membranous expression pattern. Overexpression of HER2 and HER3 was observed in 6 % (13/224) and 39 % (90/230) of EHCCs, respectively. Membranous HER2 overexpression occurred more frequently in intraductal papillary neoplasms with an associated invasive carcinoma than in tubular adenocarcinomas (P = 0.02). HER3 protein was more commonly overexpressed in nodular and infiltrative than in papillary tumors (P = 0.03). HER3 overexpression was associated with decreased survival in both univariate (P = 0.01) and multivariate (P = 0.008) analyses, whereas HER2 overexpression was not associated with survival. HER2 and HER3 are overexpressed in subsets of EHCC patients. Notably, HER3 overexpression is correlated with decreased patient survival, suggesting that HER3 constitutes a prognostic factor as well as a potential candidate for targeted therapy.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 10/2012; · 2.49 Impact Factor
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ABSTRACT: BACKGROUND: Small intestinal adenocarcinomas (SACs) are rare malignancies of the alimentary tract with uncertain carcinogenesis. METHODS: We investigated the expression of deleted in pancreatic cancer 4 (DPC4) in 188 cases of surgically resected SACs, using tissue microarray technology. RESULTS: Twenty-four of the 188 tumors showed complete loss of Smad4/DPC4 expression in cytoplasm (score, 0; 12.8%). Eighty-four and 31 cases were moderately and strongly positive, respectively (score, 2 and 3; 44.7% and 16.5%, respectively) and 49 cases were focally or weakly stained (score, 1; 29.1%). Immunohistochemistry analysis showed that the expression of Smad4/DPC4 was related to an increased risk of lymphatic invasion but not to other clinicopathological features of the tumors (tumor location, differentiation, growth pattern, T stage, direct invasion, vascular invasion, and nodal metastasis). There was no significant association between Smad4/DPC4 expression and patient survival. CONCLUSIONS: The present research is the first study to evaluate Smad4/DPC4 expression in a large sample of SACs with clinicopathologic correlation. Future studies should focus on the immunohistochemical and molecular characteristics of SACs to clarify their tumorigenesis.
Korean journal of pathology. 10/2012; 46(5):415-422.
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ABSTRACT: BACKGROUND: Brunner's gland proliferating lesions, termed Brunner's gland hamartoma, hyperplasia, or adenoma, is regarded as a benign condition. However, cancerous changes have been reported in Brunner's gland proliferating lesions. AIMS: The purpose of this study was to define the characteristic features of Brunner's gland proliferating lesions and evaluate any observed cancerous changes. METHODS: We analysed clinicopathologic features and mucin expression in 25 Brunner's gland proliferating lesions. RESULTS: Brunner's gland proliferating lesions were categorized as Brunner's gland hamartoma or hyperplasia according to their tissue components. Brunner's gland hamartoma commonly occurred in the duodenal bulb and exhibited a polypoid appearance, while Brunner's gland hyperplasia was primarily observed in the second portion of duodenum as a submucosal mass and was accompanied by symptoms more frequently than Brunner's gland hamartoma. The Brunner's glands in Brunner's gland proliferating lesions exhibited various morphologic characteristics, from normal-appearing glands to sclerotic glandular foci with atypia. Changes in MUC5 expression observed in both sclerotic glandular foci and dilated Brunner's glands suggest that they might share a common mechanism and are associated with gastric foveolar metaplasia. CONCLUSIONS: These findings indicate that most Brunner's gland proliferating lesions are either hamartoma or hyperplasia, and that true neoplastic Brunner's gland proliferating lesions are very rare. Thus, Brunner's gland adenomas or carcinomas arising in Brunner's gland proliferating lesions should be confirmed by ancillary tests, including immunostaining or molecular analysis, in addition to morphological criteria.
Digestive Diseases and Sciences 07/2012; · 2.12 Impact Factor
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ABSTRACT: Overexpression of metastatic tumor antigen-1 (MTA-1) is suggested to be associated with frequent postoperative recurrence and poor survival of hepatocellular carcinoma (HCC) patients. In this study, we intended to determine clinical factors predisposing the overexpression of MTA-1 in patients with hepatitis B virus (HBV)-associated HCC and also examine whether MTA-1 overexpression affects the survival periods of these patients treated with curative surgical resection.
A total of 303 patients with HBV-associated HCC who underwent curative surgical resection were subjected. The expressions of MTA-1 in HCC and surrounding non-tumor liver tissues were evaluated using the immunohistochemical method. The clinical, radiological and histological characteristics of the patients were analyzed in relation to the expression of MTA-1 to find predisposing factors of MTA-1 overexpression.
MTA-1 was overexpressed in 104 HCC tissues (34.3 %) and none of the surrounding non-tumor tissues. Clinically, MTA-1 overexpression was significantly associated with younger age, female gender, higher serum alpha-fetoprotein level, and Child-Turcotte-Pugh class A. Also, portal vein thrombosis, microvascular invasion, capsular invasion and poorly histological differentiation were associated with overexpression of MTA-1. The cumulative survival rates were significantly lower in patients with MTA-1 overexpression compared with those in the MTA-1 negative group (P = 0.03). In addition to the overexpression of MTA-1, the presence of microvascular or capsular invasion was a significant factor determining the poor survival of the patients with HBV-associated HCC after curative resection.
MTA-1 is overexpressed in patients with HBV-associated HCC of invasive nature. MTA-1 overexpression is associated with shorter survival periods of patients with HBV-associated HCC after curative resection.
Digestive Diseases and Sciences 07/2012; 57(11):2917-23. · 2.12 Impact Factor
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ABSTRACT: A 45-year-old male with alleged asymptomatic hepatic hemangioma of 4 years duration had right upper-quadrant pain and was referred to a tertiary hospital. Computed tomography and magnetic resonance imaging scans revealed a hypervascular mass of about 7 cm containing intratumoral multilobulated cysts. A preoperative liver biopsy was performed, but this failed to provide a definitive diagnosis. The patient underwent a partial hepatectomy of segments IV and VIII. The histologic findings revealed multifocal proliferation of flattened or cuboidal epithelioid cells and a highly vascular edematous stroma. Immunohistochemistry findings demonstrated that the epithelioid tumor cells were positive for cytokeratin (AE1/AE3), vimentin, calretinin, and cytokeratin 5/6, and were focally positive for CD10, and negative for WT1 and CD34, all of which support their mesothelial origin. Immunohistochemistry for a mesothelial marker should be performed for determining the presence of an adenomatoid tumor when benign epithelioid cells are seen.
Clinical and molecular hepatology. 06/2012; 18(2):229-34.
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ABSTRACT: Intraductal papillary neoplasm of the bile duct (IPNB) is a biliary neoplasm with predominant intraductal papillary growth and various degrees of malignant transformation. Although IPNB has been recently added to the WHO classification, the classification system needs refinements.
We retrospectively reviewed 93 non-invasive and invasive IPNB cases, surgically resected from 1996 to 2006. To further characterize their biologic behavior, we modified the WHO classification into a 4-tier category system in which non-invasive IPNB cases with complex fused or cribriform papillae were separately designated. Epithelial types such as intestinal, gastric, pancreatobiliary, and oncocytic type were determined by morphology and mucin core protein immunohistochemistry. Resection margins were classified based on their microscopic appearances. The prognostic values of mucinous histology and MUC1 protein expression were also determined.
IPNB with complex fused or cribriform papillae showed a worse prognosis than IPNB with simple papillae and one such case showed a metachronous metastasis. In addition, a positive surgical margin including dysplasia was associated with worse outcomes. Among the invasive IPNB cases, MUC1-positive tumors were more aggressive than MUC1-negative tumors.
We propose that non-invasive IPNB with complex fused or cribriform papillae might be better classified as mucosa-confined cholangiocarcinoma rather than IPNB with high grade dysplasia. In addition, aggressive further resection is recommended when a positive surgical margin including dysplasia is reported during intraoperative histopathological evaluation.
Journal of Hepatology 05/2012; 57(4):787-93. · 9.26 Impact Factor
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Young-Joo Jin,
Kang Mo Kim,
Shin Hwang,
Sung Gyu Lee,
Tae-Yong Ha,
Gi-Won Song,
Dong-Hwan Jung,
Ki-Hun Kim, Eunsil Yu,
Ju Hyun Shim,
Young-Suk Lim,
Han Chu Lee,
Young-Hwa Chung,
YungSang Lee,
Dong-Jin Suh
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ABSTRACT: We evaluated efficacy of exercise and diet modification for steatosis improvement of non-obese non-alcoholic fatty liver disease (NAFLD) patients.
We analyzed retrospectively the clinical and histological parameters of consecutive living liver donors, who experienced repeated liver biopsies due to steatosis and were treated using exercise and diet modification.
From 1995 to 2009, among a total of 1365 potential living liver donors with NAFLD seen on the initial liver biopsy, 120 consecutive donors with steatosis ≥ 30% or an estimated donor-recipient weight ratio < 0.8, underwent exercise and diet modification and received follow-up liver biopsy at our institution. Median age was 33 years, and median interval between the two consecutive biopsies was 10 weeks (range, 1-39). At the time of initial biopsy, the number of normal body mass index, overweight, and obese donors was 49 (40.8%), 65 (54.2%), and 6 (5.0%), respectively. After lifestyle modification, weight reduction and steatosis improvement were observed in 92 (76.7%) and 103 (85.8%) donors, respectively, at the time of follow-up biopsy. On multivariate analysis, initially higher steatosis (hazard ratio [HR] 1.03, P = 0.02), total cholesterol reduction ≥ 10% (HR 5.59, P = 0.02), and weight reduction ≥ 5% (HR 6.63, P = 0.03) were significantly associated with ≥ 20% steatosis improvement in 120 donors with NAFLD, after exercise and diet modification.
Exercise and diet modification were effective in reducing steatosis in potential living liver donors with non-obese NAFLD. Total cholesterol reduction ≥ 10% could be used as a non-invasive predictor for steatosis improvement in liver donors with NAFLD, after exercise and diet modification.
Journal of Gastroenterology and Hepatology 05/2012; 27(8):1341-7. · 2.87 Impact Factor
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Mijin Gu,
Young Kyung Bae,
Ae Ri Kim,
Seung-Mo Hong, Eunsil Yu,
Jihun Kim,
Kee-Taek Jang,
Hee-Kyung Chang,
Eun Sun Jung,
Han-Ik Bae, [......],
Young-Ha Oh,
Kyu Yun Jang,
Sun-Young Jun,
Dae Woon Eom,
Kye Won Kwon,
Gyeong Hoon Kang,
Jae Bok Park,
Soonwon Hong,
Soo Jin Jung,
Ji Shin Lee
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ABSTRACT: Background/Aims: Although primary small intestinal carcinoma (SIC) is morphologically similar to colorectal carcinoma and shares many of the genetic changes of carcinogenesis, little is known about the role of defective mismatch repair (MMR) genes involved in the SIC. The aim of this study is to investigate the role of defective MMR genes and correlation between clinicopathological factors and loss of MMR protein in SIC. Methodology: A total of 195 SIC cases were collected from 20 institutions in Korea and tissue microarrays (TMA) were made. The loss of expression of hMLH1, hMSH2 and hMSH6 was examined by immunohistochemistry (IHC). Results: The loss of expression of hMLH1, hMSH2 and hMSH6 was identified in 25/193 (13.0%), 25/193 (13%) and 29/195 (15%), respectively. The loss of hMSH2 expression was associated with retroperitoneal seeding. Patients with loss of hMSH6 expression had a tendency to invade deeply and a higher frequency of pancreas invasion. The loss of hMSH6 expression was associated less frequently with peritumoral adenoma. There was no survival difference by MMR protein expression status. Conclusions: The loss of MMR protein was associated with some distinct clinicopathological features. MMR pathway seems to be major pathway in carcinogenesis of SICs. MMR defect seems to be related with sporadic-microsatellite instability (MSI).
Hepato-gastroenterology 03/2012; 59(119). · 0.66 Impact Factor
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Jing Xu,
Saya Igarashi,
Motoko Sasaki,
Takashi Matsubara,
Norihide Yoneda,
Kazuto Kozaka,
Hiroko Ikeda,
Jihun Kim, Eunsil Yu,
Osamu Matsui,
Yasuni Nakanuma
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ABSTRACT: Intrahepatic cholangiocarcinomas (ICCs) are usually adenocarcinomas with fibrotic and hypovascular stroma. Intrahepatic cholangiocarcinomas in cirrhosis and precirrhotic liver (ICC-cirrhosis) are increasingly being diagnosed, and can display hypervascular enhancement resembling a hepatocellular carcinoma on dynamic imaging.
In this study using ICC-cirrhosis (71 cases), ICC with non-specific reactive changes (ICC-reactive) (72 cases) and the cholangiocarcinoma component of combined hepatocellular cholangiocarcinoma (HCC-ICC) (30 cases), we tried to compare the tumour vasculature.
It was found that ICC-cirrhosis and the cholangiocarcinoma component of HCC-ICC showed a higher density of arteries and microvessels (1.59 ± 0.58/mm(2) (mean ± SD) and 140 ± 43/mm(2) in ICC-cirrhosis and 1.74 ± 0.67/mm(2) and 131 ± 46/mm(2) in the cholangiocarcinoma component of HCC-ICC) than in ICC-reactive (1.26 ± 0.61/mm(2) and 103 ± 45/mm(2) ). Dynamic computed tomography (CT) and magnetic resonance imaging (MRI) showed that a majority of ICC-cirrhosis displayed strong hypervascular enhancement, whereas one-third of ICC-reactive each showed strong, weak and no or minimal enhancement respectively. The increased vascular density was positively correlated with enhanced arterial phase of dynamic CT and MRI.
The density of arteries and microvessels of ICC-cirrhosis was higher than that in ICC-reactive and comparable to that in the cholangiocarcinoma component of HCC-ICC, and the higher density of arteries and microvessels in ICC may be responsible for the hypervascular enhancement of ICC-cirrhosis.
Liver international: official journal of the International Association for the Study of the Liver 03/2012; 32(7):1156-64. · 3.82 Impact Factor
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ABSTRACT: Objectives: The aim of this study was to examine whether interferon-α (IFN-α) therapy may reduce the occurrence of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) and to determine its effect based on responsiveness to IFN-α therapy. Methods: A total of 641 biopsy-proven CHB patients were treated with IFN-α2b. They were followed by biochemistry and/or imaging studies at 3- to 6-month intervals for a median period of 113 months (range 6-222). Results: HCC was detected in 22 patients and 5- and 10-year cumulative occurrence rates were 0.4 and 3.2%, respectively. In univariate analysis, age (p < 0.001), serum AFP levels (p < 0.001), and serum HBV-DNA levels (p = 0.002) at baseline were associated with HCC development. HCC occurred less frequently in biochemical responders at the end of treatment than in non-responders (p = 0.001). However, virologic response was not associated with HCC development. Multivariate analysis showed that poor biochemical response (p = 0.007) as well as older age (p = 0.018) and a higher serum AFP level (p < 0.001) remained independent predisposing factors of HCC development in CHB patients treated with IFN-α. Conclusion: The results suggest that the biochemical but not virologic response to IFN-α therapy reduces independently the occurrence of HCC in patients with CHB.
Digestive Diseases 01/2012; 30(6):568-73. · 2.37 Impact Factor
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ABSTRACT: Objective: The associations between arrest-defective protein 1 (ARD1) gene expression and the clinicopathological characteristics and clinical outcomes of 94 patients undergoing hepatectomy for hepatocellular carcinoma (HCC) were investigated. Methods: ARD1 mRNA levels in HCC and corresponding non-cancerous tissues were quantified by real-time PCR. The gene expression of the tumor relative to that in the non-tumor tissues was calculated using the 2(-)(ΔΔ)(CT) method. The subjects were classified into high expression (2(-)(ΔΔ)(CT) > 1, n = 38) and low expression (2(-)(ΔΔ)(CT) ≤ 1, n = 56) groups. Results: The HCCs did not differ from matched liver tissues in terms of ARD1 mRNA levels. The high expression group had more often microvascular invasion than the low expression group (32 vs. 14%; p = 0.045). The two groups did not differ significantly in terms of other patient or tumor variables. The median follow-up period was 92.1 months. The 5-year recurrence-free and overall survival rates were 34 and 76% for the high expression group, respectively, which were similar to the rates of the low expression group (46 vs. 73%, p = 0.98 and p = 0.52, respectively). Conclusions: Intratumoral ARD1 mRNA overexpression was involved in the microvascular invasion process in patients with HCC, although it did not associate strongly with postresectional outcomes.
Digestive Diseases 01/2012; 30(6):603-8. · 2.37 Impact Factor
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ABSTRACT: Intrahepatic cholangiocarcinomas (ICCs) are known to arise in cases of non-biliary, chronic advanced liver disease (CALD), but their clinicopathological features remain unexplored. The aim of this study was to compare the histological and immunohistochemical ICCs arising inCALD with those arising in livers with non-specific reactive (NSR) changes.
Seventy-one cases of ICC arising in CALD were compared with ICCs arising in livers with NSR changes, including normal livers (72 cases) and the cholangiocarcinomatous (CC) component of hepatocellular cholangioncarcinomas (HC-CCs) (30 cases). The expression of mucin was higher in ICC with NSR changes, whereas it was relatively low in ICC with CALD and the CC component of HC-CC. The expression of biliary markers [cytokeratin (CK)7, CK19, epithelial membrane antigen, and epithelial cell adhesion molecule (EpCAM)] was lower in CC with CALD and in the CC component of HC-CC than in CC with NSR changes. The expression of hepatic progenitor cell markers [neural cell adhesion molecule (NCAM) and c-kit] was higher in ICC with CALD and the CC component of HC-CC than in ICC with NSR changes. EpCAM and CK19 were constantly expressed in cultured CC cells, whereas NCAM was infrequently expressed in cultured CC cells.
The carcinogenesis of ICC arising in CALD and the ICC component of HC-CC, each showing similar features, may involve hepatic progenitor cells.
Histopathology 12/2011; 59(6):1090-9. · 3.08 Impact Factor
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Jong Gi Choi,
Young-Hwa Chung,
Jeong A Kim,
Young-Joo Jin,
Won Hyung Park,
Danbi Lee,
Ju Hyun Shim,
Yoon Seon Lee,
Dong Dae Seo,
Myoung Kuk Jang,
Kang Mo Kim,
Young-Suk Lim,
Han Chu Lee,
Yung Sang Lee, Eunsil Yu,
Young Joo Lee
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ABSTRACT: In this study the authors intended to investigate the relationship between intrahepatic hepatitis B virus (HBV)-DNA concentrations and posthepatectomy recurrence of HBV-associated hepatocellular carcinoma (HCC).
High HBV-DNA level is strongly associated with HCC development in chronic HBV infection and considered to be a risk factor of HCC recurrence.
A total of 109 patients with HBV-associated HCC who underwent curative surgical resection were followed up every 3 to 6 months for a median of 82 months. Intrahepatic total HBV-DNA titer was measured in HCC and surrounding liver tissues using a TaqMan probe-based real-time polymerase chain reaction method. HBV-DNA titers in HCC and surrounding liver were compared in accordance with patients' clinical, radiologic, and histopathological characteristics. The relationships between HBV-DNA titers in HCC or surrounding liver tissues and cumulative HCC recurrence rates were determined.
Of the 109 patients, 67 (62%) showed posthepatectomy recurrence of HCC. In all patients, total HBV-DNA titers were significantly higher in HCCs than in surrounding liver tissues (P=0.019). HCC recurred more frequently in patients with higher than those with lower HBV-DNA titers in surrounding liver tissues (P=0.009). In contrast, the HCC recurrence rates were similar in patients with higher and those with lower HBV-DNA titers in HCC specimens (P=0.301). Multivariate analysis showed that tumor size >5 cm (P=0.008), the presence of portal vein thrombus (P=0.001), and high HBV-DNA titer in surrounding liver tissues (P=0.002) were independent risk factors for posthepatectomy HCC recurrence in patients with HBV-associated HCC.
In patients with HBV-associated HCC, high HBV-DNA titer in surrounding liver rather than in the HCC itself is associated with posthepatectomy HCC recurrence after curative surgical resection.
Journal of clinical gastroenterology 11/2011; 46(5):413-9. · 2.21 Impact Factor
