Masahiko Okudaira

Kitasato University, Edo, Tōkyō, Japan

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Publications (83)82.9 Total impact

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    Masahiko Okudaira · Makoto Ohbu · Kunio Okuda ·
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    ABSTRACT: Idiopathic portal hypertension (IPH) is a disorder of unknown etiology, clinically characterized by portal hypertension (varices and portosystemic collateral vessels), splenomegaly, and anemia (hypersplenism). A similar disorder is called noncirrhotic portal fibrosis in India, and hepatoportal sclerosis seems to be the counterpart in the United States. This disease is uncommon in developed countries. Middle-aged women are more prone to IPH in Japan. The liver has no cirrhosis or pseudonodule formation, and the principal pathologic changes are considerable portal fibrosis, devastation of intrahepatic terminal portal radicles, and parenchymal atrophy of the liver secondary to portal malperfusion. The characteristic portal hemodynamics include intrahepatic presinusoidal portal hypertension, increased splenic and portal vein blood flow, and increased intrahepatic portal resistance. The prognosis is generally good depending on the management of bleeding varices. Although the etiology is obscure, certain immunologic abnormalities seem to play an etiologic role in Japanese patients, and the incidence has markedly declined in recent years in Japan, indirectly suggesting a role of infection. The theory that IPH represents an undiagnosed intrahepatic portal vein thrombosis is refuted.
    Seminars in Liver Disease 03/2002; 22(1):59-72. DOI:10.1055/s-2002-23207 · 4.95 Impact Factor
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    ABSTRACT: The Japanese Ministry of Health and Welfare Research Committee on Aberrant Portal Blood Flow carried out an epidemiological survey and clinical study on Budd-Chiari syndrome in 1990. In the primary survey for determining the prevalence of the disease, a questionnaire was sent to all major hospitals throughout Japan and 160 cases seen in 1989 were compiled. More epidemiological details were obtained in 87 of these 160 cases. The number of patients with Budd-Chiari syndrome in this country was estimated to be about 300 (prevalence of 2.4/million) with about 20 new cases occurring every year. In the clinical study, 157 authentic cases of Budd-Chiari syndrome studied in 15 years (1975-89) were analyzed. There were 87 males (average age, 36.4 years) and 70 females (46.5 years), and the average period from the likely onset to the first medical consultation was 6.6 years, suggesting that these patients were mostly chronic cases. The main clinical features were hepatomegaly, leg edema, ascites and venous dilatation over the trunk. Abdominal pain was recorded in only four (2.5%). There were 16 (10.2%) with known identifiable etiologies. Of the patients 93% showed an obstructing lesion of various thickness in the hepatic portion of the inferior vena cava. Only nine (5.7%) had hepatic vein obstruction without caval lesions. Thus, the majority of Budd-Chiari syndrome patients in Japan are idiopathic, having an obstructing lesion in the inferior vena cava. The main causes of 33 deaths (21%) were liver failure, variceal bleeding and hepatocellular carcinoma. Hepatocellular carcinoma occurred in 10 (6.4%) in the 15-year period. However, the incidence of Budd-Chiari syndrome among all cases of hepatocellular carcinoma was less than 1% in the survey made by the Liver Cancer Study Group of Japan.
    Journal of Hepatology 02/1995; 22(1):1-9. DOI:10.1016/0168-8278(95)80252-5 · 11.34 Impact Factor
  • Makoto Ohbu · Masahiko Okudaira · Kiyoharu Watanabe · Satoshi Kaneko · Tomoko Takai ·
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    ABSTRACT: Aberrant vessels, which are defined as dilated blood vessels immediately adjacent to the peripheral portal tract, appear under conditions of extrahepatic portal obstruction and nodular regenerative hyperplasia as well as idiopathic portal hypertension. Our study was undertaken to compare their morphological aspects in these three disease cases. Aberrant vessels were found in 84% of cases of idiopathic portal hypertension, 67% of cases of extrahepatic portal obstruction infantile type, 78% of cases of extrahepatic portal obstruction adult type and 83% of cases of nodular regenerative hyperplasia. They were divided into three types: type I--no communication with the portal vein, the lumen of which is normally open; type II--communication with the portal vein; and type III--no communication with the portal vein, which is occluded. The most common types of aberrant vessel were type III in idiopathic portal hypertension (51%), type I in extrahepatic portal obstruction infantile type (46%), type II in extrahepatic portal obstruction adult type (43%) and type III in nodular regenerative hyperplasia (45%). Serial sections revealed transition between types I, II and III, at frequencies between types II and III, types I and II, and types I and III of 35.7%, 33.7% and 30.6%, respectively. Aberrant vessels demonstrated the same immunoreactivity as portal veins for collagen type IV, laminin, factor VIII and ulex europaeus agglutinin-I. They were concluded to arise from the vasa septalis or inlet venules, which would be used as intrahepatic shunts draining portal blood flow blocked by stenosed portal veins. Increased portal pressure would be expected to enhance development of aberrant vessels.(ABSTRACT TRUNCATED AT 250 WORDS)
    Hepatology 08/1994; 20(2):302-8. DOI:10.1002/hep.1840200206 · 11.06 Impact Factor
  • M Okudaira · E Atari · M Oubu ·
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    ABSTRACT: Cirrhosis of the liver is a principally a morphological entity, and it has been assumed to be an end-stage condition of all chronic active liver diseases. Morphologically, liver cirrhosis can be defined briefly as "a pathological condition characterized by diffuse pseudonodule formation throughout the entire liver". Fundamental pathogenetic changes in the cirrhotic process are hepatic necrosis, increase of connective tissue and regeneration of hepatocytes. For the sake of convenience, liver cirrhosis is classified into two groups; common and specific types. The former included postnecrotic, posthepatitic, alcoholic and mixed types of cirrhosis, and congestive, biliary, parasitic cirrhosis and Wilson disease were grouped into the latter. It should be mentioned that morphological diagnostic criteria is much more rigid for the common types than those of the specific type. Special stress has been laid on the importance of structural changes not only in the parenchymal disorganizations, but also in the stromal vascular changes in the cirrhotic process.
    Nippon rinsho. Japanese journal of clinical medicine 02/1994; 52(1):5-10.
  • Makoto Saegusa · Yasuo Takano · Masahiko Okudaira ·
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    ABSTRACT: Twenty hepatic infarction cases selected from 5420 consecutive autopsy cases were investigated to clarify the pathogenetic aspects of this disease. Additional postmortem angiological studies of 24 normal human livers obtained at autopsy were also further performed to analyse the effects of blocking vascular structures on lesion development. Seventeen of the 20 cases (85%) were clinically associated with systemic circulatory insufficiency, especially hepato- and/or renal failure. Histopathologically, there was a significantly closer relationship between the location of infarcted regions and portal vein thrombosis than with either hepatic vein thrombosis or hepatic arterial damage. The borders between infarcted regions and surviving hepatic parenchyma were located around central veins, corresponding with the microcirculatory periphery of the portal venous system. Postmortem angiographic studies revealed that hepatic lobuli mainly consist of portal vein branches. Moreover, postmortem embolization studies of six normal livers using glass beads and barium-gelatin injection showed that physical occlusion of portal vein branches produced defects in broad areas of the hepatic parenchyma. Therefore, it is suggested that the development of hepatic infarction principally depends on disturbances of the portal venous system. In addition, systemic circulatory insufficiency, which reduces the intrahepatic blood flow, probably contributes greatly to the development of hepatic infarction.
    Liver International 11/1993; 13(5):239-45. DOI:10.1111/j.1600-0676.1993.tb00638.x
  • Y Takano · M Okudaira · B.V. Harmon ·
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    ABSTRACT: The effects of the microtubule disrupting drugs (MDD) vinblastine, vincristine and colchicine on a human lymphoma cell line, BM 13674, were investigated. Twelve hours after administration of vinblastine (10(-3) mg/ml), vincristine (10(-2) mg/ml) or colchicine (10(-2) mg/ml), cell death with the characteristic morphology of apoptosis was observed in 71.6%, 82.2% and 76.9% of the cells respectively. The mode of death was confirmed as apoptotic by the occurrence of internucleosomal DNA cleavage, which was demonstrated by agarose gel electrophoresis. For the purpose of casting light on the mechanism involved, inhibition tests were performed on apoptosis induced by one of these drugs, vinblastine, using a phorbol ester (PDBu), zinc sulphate and cycloheximide. PDBu, an activator of protein kinase C, and zinc sulphate, a putative inhibitor of the endonuclease were thought to be responsible for internucleosomal DNA cleavage; both markedly reduced the induction of apoptosis. The protein synthesis inhibitor cycloheximide, on the other hand, had no inhibitory effect. Moreover, cycloheximide treatment per se enhanced apoptosis. This suggests that new protein synthesis is not required for the execution of vinblastine-induced apoptosis. Such a finding is in accord with recent reports suggesting that the "death program" within many cell types may be primed but unable to proceed due to concomitant production of specific "apoptotic inhibitors". It is suggested that phorbol esters prevent vinblastine-induced apoptosis in the BM 13674 cells by activating one or more of these specific "apoptotic inhibitors", possibly by means of PKC-mediated phosphorylation.
    Pathology - Research and Practice 04/1993; 189(2):197-203. DOI:10.1016/S0344-0338(11)80092-0 · 1.40 Impact Factor
  • T Suzuki · Y Takano · A Kakita · M Okudaira ·
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    ABSTRACT: Forty-three cases of gallbladder cancer were investigated for c-erbB-2 gene amplification and c-erbB-2 protein over-expression using a combined polymerase chain reaction (PCR) and immunohistochemical approach. Thirty out of 43 cases (69.6%) demonstrated c-erbB-2 gene amplification, the positive rates being 50% and 77.4% for twelve early cancers and thirty-one advanced cancers, respectively (P < 0.05). However, there was no statistically significant correlation between c-erbB-2 gene amplification and histologic grade of differentiation or lymph node metastasis. Fourteen out of 43 cases (32.6%) showed positive immunoreactivity reflecting c-erbB-2 protein over-expression but again no statistically significant correlation was found with grade of differentiation, invasion or lymph node metastasis. Neither the c-erbB-2 gene nor the protein revealed any close relation to prognosis. In contrast, histopathologic findings for histologic grade of differentiation, invasion grade and lymph node metastasis showed good correlations to prognosis and between themselves. In conclusion, while c-erbB-2 gene and protein in gallbladder cancers might be related to invasiveness, they are not applicable as predictive factors for prognosis.
    Pathology - Research and Practice 04/1993; 189(3):283-92. DOI:10.1016/S0344-0338(11)80511-X · 1.40 Impact Factor
  • T Suzuki · Y Takano · K Yamashita · K Sato · A Kakita · M Okudaira ·
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    ABSTRACT: Eight secondary malignancies developing after renal transplantation were investigated in terms of a possible role of the Epstein-Barr virus (EBV). In five cases, four gastric cancers and one colonic cancer, the presence of EBV was proven by the polymerase chain reaction (PCR), all four gastric lesions being confirmed to have a massive EBV infection by in situ hybridization. Two cases demonstrated monoclonal infection with EBV, as indicated by a single band of the lymphocyte-defined membrane antigen tandem-repeat gene using PCR, and were immunohistochemically positive for the latent membrane protein 1. Our series suggests that gastrointestinal cancer predominates as a secondary malignancy in states of induced severe immunosuppression, and that EBV may play an important role in tumorigenesis as an oncovirus.
    Journal of Cancer Research and Clinical Oncology 02/1993; 119(10):627-9. DOI:10.1007/BF01372727 · 3.08 Impact Factor
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    ABSTRACT: Expression of p53 and c-myc was investigated and compared with cell proliferative activity in a series of 40 hepatocellular carcinomas (HCC), by means of enhanced immunohistochemistry. p53 expression was demonstrated in 5 out of 40 HCC (12.5%) with the incidence increasing in 5 out of 40 HCC (12.5%) with the incidence increasing in proportion to the histological grading of malignancy: thus, 0% of well-differentiated, 6.9% of moderately differentiated and 33.3% of poorly differentiated lesions were positive. The proliferating-cell nuclear antigen (PCNA) labeling index also showed a statistically significant increase with this grading. Distribution patterns of PCNA-positive cell were divided into four types: scatter, marginal, mosaic and diffuse. Four HCC cases, predominantly of the poorly differentiated type, exhibited the diffuse pattern. Generally, p53 overexpression corresponded well with PCNA positivity. In contrast, there was no correlation between c-myc overexpression, found in 19 out of 40 HCC (47.5%), and histological grading of HCC or PCNA labeling index. The distribution pattern of c-myc-positive HCC cells was also different from that of PCNA and p53. Our results suggest that p53 overexpression closely relates to proliferation of HCC cells. Furthermore, there may be a consistent difference in regulatory mechanisms between p53 and c-myc expression in multistep hepatocarcinogenesis.
    Journal of Cancer Research and Clinical Oncology 02/1993; 119(12):737-44. DOI:10.1007/BF01195346 · 3.08 Impact Factor
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    ABSTRACT: The frequency of a visceral mycosis grows definitely higher with an immunocompromised host. Invasive fungal infection can be controlled by means of development of early diagnosis and antifungal therapy. In these types of cases, it is difficult to establish an antemortem diagnosis of invasive pulmonary aspergillosis and most of them were diagnosed postmortem. A patient was diagnosed as aspergillosis from the clinical and serological features. This patient underwent successful therapy during remission induction therapy of acute myelocytic leukemia (AML). A 26-year-old male was admitted to our hospital because of leukocytosis with a diagnosis of AML made by reviewing peripheral blood smears and bone marrow aspirate. After remission induction therapy, he was still febrile in spite of treatment with a broad spectrum antibiotics and empiric therapy of fluconazole. Unfortunately shadowing appeared on the chest radiograph and aspergillus antigen was detected from the serum and the sputum. Consequently, the patient who suffered from invasive pulmonary aspergillosis was diagnosed and treated with intravenous amphotericin B and flucytosine. The radiological shadow improved but AML relapsed, therefore, remission induction therapy of AML was started again but he died of sepsis caused MRSA. In the postmortem histopathological examination the lung tissues, the hyphae could not be confirmed while, in immunohistochemical examinations of the lesion at the left S8, aspergillus antigens were detected around the small necrotic lesions and in the polymorphologic giant cells. We emphasize that invasive pulmonary aspergillosis is very difficult to diagnose whereas active examinations and clinical early diagnosis may lead to more effective therapy and the prognosis.
    Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases 02/1993; 67(1):85-91. DOI:10.11150/kansenshogakuzasshi1970.67.85
  • T Suzuki · Y Takano · Y Kida · M Okudaira ·
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    ABSTRACT: Silver-binding nucleolar organizer regions (AgNOR) were investigated and compared in 43 cases of gall-bladder cancers and 10 normal gall-bladder samples using an image analyzer. The mean numbers of AgNOR per nucleus (AgNOR number) were 3.28 +/- 1.38 in the gall-bladder cancers and 1.86 +/- 0.20 in the normal gall-bladder cases. The respective mean areas of AgNOR per nucleus (AgNOR area) were 6.96 +/- 3.78 microns2 and 1.89 +/- 0.21 microns2. The differences were statistically significant (P < 0.0001) for both parameters. In addition, increased frequency and enlargement were both apparently correlated with poor prognosis (P < 0.011 and P < 0.046, respectively), with AgNOR number and AgNOR area showing tendencies for increase in cases of histologically high grade malignancy, advanced cancer and regional lymph node involvement. In conclusion, AgNOR number and AgNOR area appear to be useful indicators for the grading of malignancies and for the prediction of gall-bladder cancer prognosis.
    Acta pathologica japonica 01/1993; 43(1-2):36-43.
  • Yutaka Kagata · Yoshiki Kida · Kiyoharu Watanabe · Masahiko Okudaira ·

    Kanzo 01/1993; 34(7):532-540. DOI:10.2957/kanzo.34.532
  • Yutaka Kagata · Masahiko Okudaira · Toshiyuki Uchikoshi · Masayuki Nakano ·

    Kanzo 01/1993; 34(9):710-717. DOI:10.2957/kanzo.34.710

  • Nippon Ishinkin Gakkai Zasshi 01/1993; 34(3):265-273. DOI:10.3314/jjmm.34.265
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    Y Takano · Y Kato · Y Sato · M Okudaira ·
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    ABSTRACT: Clonal immunoglobulin (Ig) heavy chain gene rearrangement in gastric reactive lymphoid hyperplasia (RLH) cases was investigated by means of the 'double' polymerase chain reaction (PCR) using formalin-fixed and paraffin-embedded tissue. Rearranged DNA sequences, formed by combinations of variable (VH) and joining (JH) regions, were amplified with oligomeric primers. One microgram of DNA extracted from formalin-fixed and paraffin-embedded tissue was applied as the 'first PCR' template and one ten-thousandth of the first PCR product was used as the 'second PCR' template. As a control study for the double PCR method, DNA isolated from frank B cell gastric malignant lymphomas was assessed. Clear single bands between 100 and 150 base pair markers in length were evident on agarose gel electrophoresis in 10 out of 13 cases (76.9%) of malignant lymphomas while 2 out of 22 cases (9%) of RLHs revealed clear single bands of the same length, suggesting malignant lymphomas; however, no histologic features of malignant lymphomas were present. It is concluded that even gastric RLH cases satisfying histopathologic criteria for benign lymphoid hyperplasia may contain occult monoclonal B cell populations suggesting a continuous and progressive spectrum of lesions contributing to B cell neoplasia.
    Pathology - Research and Practice 01/1993; 188(8):973-80. DOI:10.1016/S0344-0338(11)81240-9 · 1.40 Impact Factor
  • Tadamichi Suzuki · Yasuo Takano · Yoshiki Kida · Masahiko Okudaira ·
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    ABSTRACT: Silver-binding nucleolar organizer regions (AgNOR) were investigated and compared in 43 cases of gall-bladder cancers and 10 normal gall-bladder samples using an image analyzer. The mean numbers of AgNOR per nucleus (AgNOR number) were 3.28 ± 1.38 in the gall-bladder cancers and 1.86±0.20 in the normal gall-bladder cases. The respective mean areas of AgNOR per nucleus (AgNOR area) were 6.96±3.78 μm2 and 1.89±0.21 μm2. The differences were statistically significant (P<0.0001) for both parameters. In addition, increased frequency and enlargement were both apparently correlated with poor prognosis (P<0.011 and P < 0.046, respectively), with AgNOR number and AgNOR area showing tendencies for increase in cases of histologi-cally high grade malignancy, advanced cancer and regional lymph node involvement.In conclusion, AgNOR number and AgNOR area appear to be useful indicators for the grading of malignancies and for the prediction of gall-bladder cancer prognosis.
    Pathology International 12/1992; 43(1‐2):36 - 43. DOI:10.1111/j.1440-1827.1993.tb02912.x · 1.69 Impact Factor
  • T Suzuki · E Atari · M Okudaira · M Yoshida · Y Hiki · A Kakita ·

    Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 12/1992; 89(11):2700-4.
  • E Atari · H Mitomi · T Kan · S Kusano · M Okudaira ·
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    ABSTRACT: We prepared experimental of small intestinal ischemia by occluding the inlet of the anterior mesenteric artery of adult mongrel dogs with balloon catheters. With these experimental models, the degree of tissue damage of the small intestinal mucosa, which became ischemic, was studied according to the different occlusion times of the anterior mesenteric artery (3, 5, 7, 10, 15 and 30 hours). As a result, ischemic mucosal lesions in the small intestine at an initial stage occurred on the antimesenteric side. In the gross findings of the mucosa when the occlusion time was within 5 hours, linear and spotted lesions appeared in a zone on the antimesenteric side. When the occlusion time was 7 hours or more, these lesions fused and the entire intestinal mucosa became a hemorrhagic lesion. By occluding the anterior mesenteric artery for 22-30 hours, all 6 experimental ischemic animals died.
    Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 09/1992; 89(8):1491-8.
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    Hideki Muramatsu · Hikaru Kume · Midori Hojo · Kikuo Iitaka · Masahiko Okudaira · Hideki Ohtani ·
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    ABSTRACT: Continuous ambulatory peritoneal dialysis (CAPD) was introduced to Japan ten years ago and was established as the treatment for end-stage renal disease along with HD. Although the incidence of peritonitis in CAPD has decreased by educating the patients and parents and the improvement of various devises of CAPD, peritonitis is still one of the major complications of CAPD. Fungus is a rare pathogen for peritonitis in CAPD, but it must be considered as a causative agent in cases of intractable peritonitis. This report describes the first case of Trichosporon beigelii (T. beigelii) peritonitis in CAPD in Japan. A nine year old boy with chronic renal failure due to bilateral vesicoureteral reflux was given CAPD treatment four years prior to admission. This patient had been admitted to our hospital frequently because of recurrent bacterial peritonitis. The peritonitis in CAPD was usually treated by changing the peritoneal fluid and antibiotic treatment. In this case T. beigelii was proved to be a pathogen of peritonitis by culture of CAPD fluid and also serum antibody titers. T. beigelii infection was successfully eradicated from the peritoneal cavity by administration of MCZ and by the removal of peritoneal catheter. The patient was switched from CAPD to HD. In the case of intractable peritonitis in CAPD, rare fungal pathogens such as T. beigelii must be considered as a causative agent.
    Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases 09/1992; 66(8):1129-32. DOI:10.11150/kansenshogakuzasshi1970.66.1129
  • I Motohashi · M Okudaira · T Takai · S Kaneko · N Ikeda ·
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    ABSTRACT: In an attempt to provide a quantitative basis for differentiation between well-differentiated hepatocellular carcinoma and hepatocellular carcinomalike lesions (focal nodular hyperplasia, regenerative nodular hyperplasia and hepatocellular adenoma), histopathological and morphometrical analyses were performed on 208 cases of various liver diseases with the aid of an image analyzer. As practical indicators for hepatocellular carcinoma, the following six morphometrical features were established: (a) nuclear shape factor of less than 0.93, (b) coefficient of variance of nuclei of more than 5%, (c) average width of trabecular cords greater than three cells, (d) nucleocytoplasmic ratio increased to more than 0.3, (e) cellular density of more than 40 liver cells and (f) individual nuclear dimension larger than 50 microns2. The manifest categories increased with dedifferentiation of cells in hepatocellular carcinoma; the number and degree of cellular and structural atypia became more prominent. Data were analyzed statistically by two multivariate analyses. Logistic analysis was able to correctly separate hepatocellular carcinoma from conditions that were not hepatocellular carcinoma, including hepatocellular carcinomalike lesions. The incidence of 13 descriptive histopathological findings such as fibrous capsule, portal triads and clear-cell clusters were also compared in hepatocellular carcinomalike lesions and hepatocellular carcinomas graded according to Edmondson's classification. Presence of a fibrous capsule, portal triads, mosaiclike patterns and tumor vessels showed statistical differences between hepatocellular carcinomalike lesions and well-differentiated hepatocellular carcinoma by the chi 2 test (p less than 0.005).
    Hepatology 08/1992; 16(1):118-26. · 11.06 Impact Factor