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Background/aims: Most-hepatocellular carcinoma patients are between 40 and 60 years of age, but an increasing number of elderly patients with hepatocellular carcinoma is expected in the future because of the increase in life expectancy seen in many countries. Since elderly patients have a high incidence of comorbid illnesses, it should be useful to examine the clinical features of these patients to select the optimal management strategy for hepatocellular carcinoma., Methodology: A retrospective review of 111 patients with hepatocellular carcinoma was undertaken to examine the clinical features of 8 patients older than 80 years of age., Results: In the 111 patients with hepatocellular carcinoma, the ratio of males to females was 81:30 and the peak incidence of hepatocellular carcinoma was noted in the seventh and eighth decades in males and females, respectively. Of these, 21 (19%) were type "B" [seropositive for hepatitis B surface antigen (HBsAg) and seronegative for antibody to the hepatitis C virus (anti-HCV)], 69 (62%) were type "C" (seronegative for HBsAg and seropositive for anti-HCV), 3 (3%) were type "B + C" (seropositive for both HBsAg and anti-HCV), and 18 (16%) were type "non-B non-C" (seronegative for both HBsAg and anti-HCV). The peak incidences of type "B" were in the sixth decade, whereas those of type "C" were in the seventh decade in both males and females. Patients with "non-B non-C" were common in their seventies. Of the 111 patients, 6 (5 males and 1 female) were older than 80 years at the time of diagnosis and 2 females became 80 years old during the course of follow-up of hepatocellular carcinoma. All but one of these patients were anti-HCV-positive, stage and clinical stage I or II according to the criteria defined by the Liver Cancer Study Group of Japan, and underwent transcatheter arterial embolization and/or transcatheter arterial infusion chemotherapy. Transcatheter arterial embolization/transcatheter arterial infusion or percutaneous ethanol injection therapy was well tolerated in these patients, and the outcome of these patients was good. However, concomitant underlying diseases other than liver diseases made it impossible or difficult to apply an aggressive management protocol for hepatocellular carcinoma in some patients., Conclusions: Our results suggest that the overall treatment of hepatocellular carcinoma in the elderly should be similar to that in younger patients, but may be restricted by the concomitant underlying diseases specific to advanced age.

Primary biliary cirrhosis (PBC) and autoimmune cholangitis (AIC) are serologic expressions of an autoimmune liver disease affecting biliary ductular cells. Previously we screened a phage-displayed random peptide library with polyclonal IgG from 2 Australian patients with PBC and derived peptides that identified a single conformational (discontinuous) epitope in the inner lipoyl domain of the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2), the characteristic autoantigen in PBC. Here we have used phage display to investigate the reactivity of PBC sera from 2 ethnically and geographically distinct populations, Japanese and Australian, and the 2 serologic expressions, PBC and AIC. Random 7-mer and 12-mer peptide libraries were biopanned with IgG from 3 Japanese patients with PBC and 3 with AIC who did not have anti-PDC-E2. The phage clones (phagotopes) obtained were tested by capture enzyme-linked immunosorbent assay (ELISA) for reactivity with affinity-purified anti-PDC-E2, and compared with those obtained from Australian patients with PBC. Peptide sequences of the derived phagotopes and sequences derived by biopanning with irrelevant antisera were aligned to develop a guide tree based on physicochemical similarity. Both Australian and Japanese PBC-derived phagotopes were distributed in branches of the guide tree that contained the peptide sequences MH and FV previously identified as part of an immunodominant conformational epitope of PDC-E2, indicating that epitope selection was not influenced by the racial origin of the PBC sera. Biopanning with either PBC or AIC-derived IgG yielded phagotopes that reacted with anti-PDC-E2 by capture ELISA, further establishing that there is a similar autoimmune targeting in PBC and AIC.

We present a 66-year-old man with unique heterotopic gastric mucosa in the intrahepatic bile duct causing hemobilia. Endoscopic retrograde cholangiography showed irregular stenosis of the left intrahepatic bile duct, and a provisional diagnosis of cholangiocarcinoma was made. Therefore, partial hepatic lobectomy and cholecystectomy were performed. Histological examination of the liver showed the presence of ectopic gastric mucosa in the intrahepatic bile duct containing mucous glands with parietal and chief cells and bile. Heterotopic gastric mucosa in the intrahepatic bile duct is a rare cause of hemobilia.

Objective: Fulminant hepatitis is a rare but fatal disease. In the present study, we examined the changes in etiology and prognosis of fulminant hepatitis in Nagasaki Prefecture, Japan between 1980 to 1999., Methods: Eighty-one patients with fulminant hepatitis admitted to our hospitals from 1980 to 1999 were examined with respect to the etiology and prognosis., Results: Fulminant hepatitis was due to hepatitis A virus in 2 (12%) cases, hepatitis B virus in 18 (22%) cases, unknown etiology in 50 (62%) cases, and drug-induced in 11(14%) cases. The number of cases in the first half of the study (1980-1989) was 47 and that of the latter half (1990-1999) was 34 cases. The incidence of fulminant hepatitis type B also decreased from 14 cases (30%) to 4 cases (12%) during these periods. The overall survival rate of fulminant hepatitis was 32%; it was equal in fulminant hepatitis type B, fulminant hepatitis of unknown etiology and fulminant drug-induced hepatitis. The survival rate of fulminant hepatitis type A was 100%, though only two cases were identified. Retrospectively, the survival rate in patients with a pre-encephalopathy period of < or = 10 days and aged < or = 39 years was significantly higher than in patients > or = 40 years of age (p<0.01). There was no difference between the two age groups when pre-encephalopathy period was > or = 11 days., Conclusions: The incidence of fulminant hepatitis especially that of fulminant hepatitis type B in Nagasaki Prefecture has decreased in recent years. The survival rate is significantly higher in younger patients with a short pre-encephalopathy period.

Objective: The diagnostic criteria of autoimmune hepatitis (AIH) were recently modified by the International Autoimmune Hepatitis Group. This study was performed to assess the impact of the revised scoring system on the diagnosis of AIH., Patients and Methods: We re-analyzed the clinical features of 89 patients diagnosed as AIH in Nagasaki Prefecture, Japan, using the revised scoring system, and compared the scores and final diagnosis with our previously published results using the original system., Results: Of the 89 patients with AIH, 40 (45%) were classified using the new system as "definite" AIH, 41 (46%) as "probable" AIH, and 8 (9%) patients were categorized as "others". Of these, 37 (42%), 35 (39%), and 4 (4%) patients who were classified as "definite", "probable", and "others" by the original system remained in the same category by the revised system, respectively. However, 3, 4, and 6 patients were re-categorized as "definite" from "probable", "others" from "probable", and "probable" from "definite", respectively. The difference in aggregate scores between the above two systems ranged from -5 to +2. The main contributing factors to the changes in aggregate AIH score were "other autoimmune disease(s)" and "interface hepatitis without lobular involvement and bridging necrosis on liver histology". However, the main contributing factors to the demotions from "definite" to "probable" and form "probable" to "others" were those related to the characteristics of biliary diseases, i.e., antimitochondrial antibody positive, biliary changes in liver histology, and alkaline phosphatase: aspartate aminotransferase ratio between 1.5 and 3.0. Moreover, two patients who had no histological evidence of AIH were both re-categorized as "others" from "probable" AIH., Conclusion: Our results indicated that the diagnosis, whether based on the revised or original system, was the same in the majority of AIH patients, but the revised scoring system excluded cases who had features suggestive of biliary diseases from "definite" AIH, and also confirmed that a diagnosis of "definite" AIH should not be made without liver histology.

Objective: Transcription factor NF-kappaB plays a pivotal role in inflammatory responses by up-regulating mRNA expression of bioactive molecules such as chemokines and adhesion molecules. The present study was designed to elucidate the implication of NF-kappaB in Helicobacter pylori-associated gastritis (HAG)., Methods: We examined 41 patients with HAG and 18 H. pylori-negative control subjects. Expression of activated NF-kappaB was studied in situ by immunohistochemistry using alpha-p65 mouse monoclonal antibody (alpha-p65 mAb), which recognizes activated NF-kappaB. To identify the cell types in which NF-kappaB was activated, we performed immunohistochemical analysis using antibodies against vascular endothelial cells, macrophages, and B and T lymphocytes. We also examined the colocalization of activated NF-kappaB with the of intercellular expression adhesion molecule-1 (ICAM-1) on endothelial cells. We measured the levels of NF-kappaB-dependent chemokines including interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), regulated on activation normal T-cell expressed and secreted (RANTES) and macrophage inflammatory protein-1alpha (MIP-1alpha) in antral mucosa by ELISA (ELISA)., Results: Activated NF-kappaB was detected in the nuclei of epithelial cells in antral mucosa, especially of patients with HAG. NF-kappaB positivity index (NF-kappaB PI), representing the percentages of epithelial cells with positive nuclear staining for activated NF-kappaB, was significantly higher in patients with HAG than in H. pylori-negative controls. NF-kappaB PI correlated significantly with histological scores of gastritis. Moreover, activated NF-kappaB was identified in the nuclei of vascular endothelial cells, macrophages, and B lymphocytes within the lamina propria in HAG. Colocalization of activated NF-kappaB with ICAM-1 expression in the same endothelial cells was demonstrated. The IL-8 levels significantly correlated with the NF-kappaB PI., Conclusions: In addition to epithelial cells, macrophages, vascular endothelial cells, and B lymphocytes contained activated NF-kappaB. In these cells, activated NF-kappaB may be involved in the inflammation process in HAG through the up-regulation of chemokines or adhesion molecules.

In primary biliary cirrhosis, autoantibodies are produced to the family of 2-oxoacid dehydrogenase complexes. These 'anti-mitochondrial' antibodies are traditionally detected by immunofluorescence but this method of detection is subjective and labour-intensive. We assessed an enzymatic mitochondrial antibody (EMA) assay based on antibody inhibition of enzymatic activity of pyruvate dehydrogenase complex in wells of microtitre plates with a colorimetric read-out. We tested 48 Australian and 1947 Japanese patients with primary biliary cirrhosis, 306 normal subjects and 691 patients with various hepatic and non-hepatic diseases. The overall sensitivity of the EMA for the diagnosis of primary biliary cirrhosis, 82%, was slightly lower than that of immunofluorescence, 90% The advantages of the EMA test include high specificity, >99%, and semi-automated features facilitating objectivity, rapidity, simplicity and economy. The EMA test could be particularly applicable to population screening for early primary biliary cirrhosis.

We compared the usefulness of a polymerase chain reaction (PCR) assay for the early diagnosis of invasive pulmonary aspergillosis with the serodiagnosis of sufficient concentrations of galactomannan using the same serum samples. A patient was treated with prednisolone for the management of hepatitis. Computed tomography (CT) scan of the chest showed the nodular shadow with a cavity containing a clear fungus ball. DNA of Aspergillus spp. from a serum sample was detected and using the same serum sample, both latex agglutination and sandwich enzyme-linked immunosorbent assay (ELISA) of galactomannan were negative. PCR assay provides an early diagnosis of invasive pulmonary aspergillosis compared with ELISA of galactomannan.

Aims/background: Autoimmune cholangitis/cholangiopathy (AIC) is an enigmatic disease marked by chronic cholangitis, antinuclear antibodies (ANA) and sero-negativity for conventionally detected antimitochondrial antibodies (AMA). We examined whether AIC is a distinct entity, an AMA-negative variant of primary biliary cirrhosis (PBC), or a cholangiopathic variant of autoimmune hepatitis (AIH) by comparing the clinical, laboratory and autoantibody profiles of 21 cases of AIC, 37 cases PBC and 16 cases of AIH from selected Japanese patients., Methods: The specificities of AMA and ANA were determined by immunofluorescence, immunoblotting and enzyme inhibition assays using various mitochondrial and nuclear autoantigens, and the frequencies for these groups were compared., Results: By clinical, biochemical and histological data, AIC and PBC were similar and both were clearly distinct from AIH. Serologically, by immunofluorescence of AMA and ANA, there was polarisation. By immunoblotting, and notwithstanding the negative test for AMA, a proportion of the AIC sera reacted with the E2 subunits of the 2-oxo-acid dehydrogenase enzyme complexes, but more particularly with the lower molecular weight E2 subunits. The antinuclear reactivity in AIC was with centromere, Sp100 and nuclear pore complex proteins as in PBC, but preferentially with the nuclear pore complex., Conclusion: Our results demonstrate that AIC and PBC are similar diseases. However this duo is of interest because, usually, among sets of autoimmune syndromes, differences in serological targetting are matched by differences in clinical presentation: AIC and PBC are an exception to this.

Apart from insulinomas, pancreatic tumors are rarely complicated by hypoglycemia and some may produce insulin-like growth factor II (IGF-II). To our knowledge, IGF-II-producing pancreatic tumors associated with hypoglycemia have not been reported previously. We describe what we believe to be the first case of "big" IGF-II-producing pancreatic acinar cell carcinoma. A 68-year-old man presented with a history of recurrent hypoglycemia. Abdominal computed tomography scan and magnetic resonance imaging showed a mass, approximately 5 cm in diameter, in the tail of the pancreas and two low-density areas in the liver. Low serum glucose was associated with low insulin levels and high levels of hormones (i.e., glucagon and IGF-II) that are functionally opposite to insulin. Although serum IGF-II level was within the normal range, most IGF-II was of the high molecular weight form, as determined by Western immunoblot analysis. Based on these findings, a diagnosis of hypoglycemia induced by IGF-II-producing pancreatic tumor was made. Surgery was not possible because of the patient's poor general condition. The patient ultimately died as a result of malignant cachexia. At autopsy, a yellowish-white tumor was found in the tail of the pancreas, and a histopathologic diagnosis of acinar cell carcinoma was made. Immunohistologically, the tumor cells contained IGF-II in an irregular staining pattern, suggesting that the hypoglycemia was caused by a pancreatic tumor producing "big" IGF-II.

Forms of hemophagocytic syndrome, which affects mainly children, vary from mild to very severe and often fatal. We describe an adult patient with hemophagocytic syndrome in whom severe liver dysfunction developed. The condition continued to deteriorate despite treatment with plasma exchange, high-dose gamma globulin, and corticosteroid therapy. Treatment with cyclosporine (2.3 mg/kg/day) dramatically improved the condition and normalized liver function. Cyclosporine reduced the serum levels of ferritin, interferon-tau, interleukin-6, and soluble interleukin-2 receptor. These findings suggest that hemophagocytic syndrome accompanied with severe liver dysfunction results from hypercytokinemia, and cyclosporine is useful in preventing a fatal outcome during the acute phase.

One of the shortcomings of percutaneous ethanol injection therapy (PEIT) for hepatocellular carcinoma (HCC) is that many sessions are necessary to accomplish the treatment. This may be caused by which the ultrasonography (US) image does not reflect correctly to the kinetics of injected ethanol into HCC nodule. It is considered that number of treatment sessions are able to be reduced if we just enough injected labelled ethanol under US into HCC nodule. Therefore, we tried PEIT by ethanol mixed with CO2 microbubble (CO2 ethanol). The injected CO2 ethanol was aquired as hyperechoic image without strong acoustic shadow to the end of injection. Consequently we could reduce the number of treatment sessions to almost 1 for lesions < or = 3 cm in diameter and markedly reduce total dose of injected ethanol. The detectable rate of CO2 ethanol leaked out HCC nodule was high. No serious complication occurred. There have been only 1 lesion of local recurrence and no case of intrahepatic and peritoneal dissemination for 11.5 months on average of observation after PEIT by CO2 ethanol (CO2PEIT). These findings suggest that CO2PEIT is useful method for reducing the number of treatment sessions and total dose of injected ethanol, moreover preventing complication by ethanol leakage.

A rare case of malignant lymphoma of the stomach after treatment for hepatocellular carcinoma (HCC) is reported. A 72-year old man presented with a large mass on the right hypochondrium, which was diagnosed as HCC associated with chronic hepatitis C with cirrhosis. The inoperable tumor was treated conservatively with cisplatin, etoposide, carboplatin, and Lipiodol infused into the hepatic artery, together with transcatheter arterial embolization. The patient presented 38 months later with features suggestive of gastric ulceration. Endoscopy and histological examination of biopsy material confirmed the presence of malignant lymphoma of the stomach. He ultimately died as a result of hepatic failure. The clinical presentation suggests that gastric lymphoma was possibly related to the lymphotropic effect of hepatitis C virus (HCV) and exacerbated by intraarterial injection of the cytotoxic drugs.

A 64-year-old man with a 5-year history of progressive systemic sclerosis (PSS) was hospitalized because of melena. Radiological and endoscopic examinations showed an ulcerative lesion with sharply demarcated and raised margins in the fornix of the stomach. Tumor markers--serum carcinoembryonic antigen (CEA, 11.3 mg/ml) and neuron-specific enolase (NSE, 38.9 ng/ml) were elevated. Histological examination of endoscopic biopsy specimens (and of necropsy specimens) showed proliferation of atypical small round cells. Immunohistological examination of these cells showed they were positive for epithelial membranous antigen (EMA), and neuron-specific enolase (NSE), but negative for UCHL1, leukocyte common antigen (LCA), anti-leukocyte B-cell (MB1), and anti-leukocyte T-cell (MT1) antigens. Based on these histological and immunohistological tests, a definite diagnosis of small cell carcinoma of the stomach with PSS was established. Our case is a rare combination of PSS and gastric small cell carcinoma. We also reviewed the literature for the association between PSS and gastric cancer in Japanese patients.

To explore the relationship between mutant p53 and Pgp expression, we have examined the levels of both proteins in human colorectal adenocarcinomas. Serial frozen sections of 40 surgical samples were stained with an anti-Pgp (MRK16) and two different anti-p53 protein antibodies (Abs), PAb421 and PAb1801. Nineteen (47.5%) of 40 samples examined were positive for Pgp, and 18 (45%) of 40 were positive for p53. The samples that stained positively with PAb421 also stained positively with PAb1801. Pgp expression was detected in 13 (76.5%) of 17 samples that were positive for p53 using PAb421 and in 15 (83.3%) of 18 samples that were positive for p53 using PAb1801. Thus, we found that p53 and Pgp were co-expressed in a significant number of samples (P < 0.002). There was no relationship between Pgp or p53 protein accumulation and histologic grade or stage. The present results demonstrate that Pgp expression is closely associated with p53 protein accumulation in human colorectal cancers. These data provide evidence to support the idea that mutant p53 activates the MDR1 gene in vivo.

The apparent coexistence of primary biliary cirrhosis (PBC) and autoimmune hepatitis in the same patient raises unresolved problems for nosology and therapy. These are exemplified by a 45-year-old Japanese woman with overlapping clinical, serological and histological features of autoimmune cholangitis and autoimmune hepatitis. The classical serological test for PBC, antimitochondrial antibody (AMA) by immunofluorescence, was atypical. By immunoblotting there was reactivity with one of the enzymes of the 2-oxo-acid dehydrogenase complex (2-OADC) family, now recognized as autoantigens responsible for AMA reactivity. Also there was reactivity by immunofluorescence for antinuclear antibodies (ANA), one showing the typical speckled pattern of anti-Sp-100 and the other the peripheral pattern of antinuclear membrane antibody, both with titres > 10(6). There was also a positive result to the lupus erythematosus (LE) cell test. Treatment with ursodeoxycholic acid was beneficial. Thus while the clinical presentation suggested the overlapping syndrome of autoimmune hepatitis and PBC, PBC eventually proved to be the likely diagnosis. We suggest that apparent cases of overlapping PBC-autoimmune cholangitis-hepatitis syndromes, after detailed testing, will mostly align with PBC.

The discovery of hepatitis C virus (HCV) has enabled the diagnosis of type C chronic liver disease, which had in the past been diagnosed as part of non-A, non-B chronic liver disease. Although most cases with chronic liver disease are caused by hepatitis B virus (HBV) or HCV infection, there are still cases of non-B, non-C chronic liver disease. Forty patients with chronic liver disease, who were seronegative for hepatitis B surface antigen and antibody to HCV, were followed for a mean period of 72 months. The clinical manifestations in these patients were compared with those reported for type B and type C chronic liver disease. Of the 40 patients, 22 were diagnosed with chronic hepatitis, 14 with liver cirrhosis and 4 with hepatocellular carcinoma (HCC). Twenty-seven (67.5%) patients showed mild alanine aminotransferase activity profiles, and the natural clinical course of most patients showed a slow progression compared with that reported for type B and type C patients. The yearly incidence of HCC was 9.7% in patients with liver cirrhosis and 3.9% in chronic hepatitis. These rates were similar to those in type B or type C patients. This suggests that our population sample contained a number of patients with type B, type C or other etiologic agent(s), because 66.7% of the patients who developed HCC had some evidence of exposure to HBV or HCV. Our results suggest that more detailed and accurate tests for detecting HBV and HCV should be considered before making the diagnosis of non-B, non-C chronic liver disease, and that there is the need to reveal unknown etiologic agent(s).

Primary biliary cirrhosis (PBC) is characterized by the presence of antimitochondrial antibodies (anti-M2), directed against the E2 subunits of the 2-oxo-acid dehydrogenase complexes (2-OADC), chiefly pyruvate dehydrogenase complex (PDC-E2). We present here a detailed study, based on a large panel of normal sera, of the specificity of tests for anti-M2 by immunofluorescence and for anti-PDC by other assays for the diagnosis of PBC. The assays for anti-PDC included immunoblotting with bovine heart mitochondria, ELISA using recombinant PDC-E2 and an enzyme inhibition assay using purified porcine PDC. The positivity rates for normal sera were 0 (0/170), 2 (4/201), 1.5 (3/198) and 0% (0/186) for immunofluorescence, immunoblotting, ELISA and the enzyme inhibition assay, respectively. The seven positive reactions detected either by immunoblotting (n = 4) or ELISA (n = 3) were negative by the other three assays and in no instance did biochemical indices give any indication of chronic liver disease. Thus, as judged by reactivity with normal sera, the specificity of a positive test for the antibody to the major M2 autoantigen (PDC-E2) is 100% for immunofluorescence and the enzyme inhibition assay, 98% for immunoblotting and 98.5% for ELISA.

The incidence and prevalence of primary biliary cirrhosis show wide geographic differences. The frequency of this disease in Japan is lower than in Northern Europe. To elucidate the immunoreactivity of serum with enzymes of the 2-oxo-acid dehydrogenase complex (2-OADC) and the M2 mitochondrial antigenic complex in Japanese patients, we examined sera from 107 patients with primary biliary cirrhosis from three geographically different regions of Japan. The sera were assayed by immunofluorescence on frozen tissue sections, immunoblotting on bovine heart mitochondria and recombinant E2 subunit of branched chain oxo-acid dehydrogenase complex (BCOADC-E2), ELISA using recombinant E2 subunit of human pyruvate dehydrogenase complex (PDC-E2) and purified porcine 2-oxoglutarate dehydrogenase complex (OGDC), and enzyme inhibition assay using procine PDC and OGDC. Of the 107 sera, 95 (88%) reacted by immunofluorescence, 102 (95%) by immunoblotting with at least one of the M2 autoantigens, although only 78 (73%) reacted with PDC-E2; 72 (67%) by ELISA with PDC-E2; and 81 (76%) with PDC by the enzyme inhibition assay. Thus, the frequency of reactivity with PDC-E2 by all assays was lower for Japanese than the reported frequency for Caucasian patients with primary biliary cirrhosis, whereas the frequency of reactivity by immunoblotting and ELISA against 2-OADC enzymes other than PDC was relatively higher. The relative frequency of reactivity of autoantibodies to the M2 autoantigens was similar for the three different regions of Japan. The different autoantibody profiles for Japanese and Caucasian patients with primary biliary cirrhosis point to immunogenetic and environmental determinants of this disease, which should provide new insights into its autoimmune origins.

Infections in immunocompromised hosts have been an important clinical problem. Patients with liver cirrhosis and/or hepatocellular carcinoma are at a high risk of infection due to multiple factors. Five hundred and two patients admitted with liver cirrhosis and/or hepatocellular carcinoma were evaluated for infection. The infection rate was not influenced by the etiology of hepatic diseases or the presence of hepatocellular carcinoma, however, it increased with the advance of clinical stages of liver cirrhosis and hepatoma. The respiratory tract and urinary tract were the most common sites of infection, being involved in 50% and 28% of cases, respectively. The major pathogens of respiratory tract infection were S. aureus, H. influenzae, and P. aeruginosa. Gram-negative bacteria was the common isolate from sputum and urine, and S. aureus was also common in gram-positive bacteria. The infection rate was high in patients who died although infections could rarely be implicated as the direct cause of death. These findings should be a guide for the clinicians in treating patients with liver cirrhosis and/or hepatocellular carcinoma who exhibit signs of infection.

A 75-year-old man was diagnosed as having a sessile tumor measuring 1.4 x 1.0 cm in size in the duodenal bulb after upper gastroduodenal series. The biopsy specimens revealed a proliferation of the adenomatous glands showing an acinar structure with papillary infolding; type III mucus, which is characteristic of Brunner's glands. Antral glands and mucus neck cells of the fundic glands were also observed in the adenomatous glands by concanavalin A staining. Thus, it was clear that the tumor had originated from the Brunner's glands. Three years and four months later, the sessile tumor had developed into a fungating ulcerated tumor via a polypoid form. The biopsy specimens revealed a papillary adenocarcinoma with foci of undifferentiated carcinoma. Retrospectively, the adenomatous glands in the biopsy taken from the sessile tumor should have been regarded as low grade carcinoma. Therefore, we propose that when a polyp or tumor shows an increase in size or change in macroscopic appearance, surgery should be considered.

A 23-year-old man with persisting high fever developed hepatosplenomegaly, lymphadenopathy and massive pericardial effusion. Immunological examination revealed a marked elevation of anti-Epstein-Barr virus antibodies (anti-viral capsid antigens IgG-antibody 1:10,240, anti-early antigens-DR IgG-antibody 1:5,120), decreased activities of Epstein-Barr virus specific cytotoxic T lymphocytes, natural killer cells and lymphokine activated killer cells. A liver biopsy showed moderate sinusoidal lymphocytosis with punched-out lesions. These findings suggested severe chronic active Epstein-Barr virus infection syndrome. The patient was treated with recombinant human interleukin-2, but it was discontinued because of an adverse reaction. Twelve months later, he died of suspected pulmonary infection.

The nuclear DNA contents of paraffin-embedded specimens of 41 cases of a hepatocellular carcinoma have been measured by means of flow cytometry. Results have indicated that 25 cases (61%) were diploid and 16 cases (39%) were aneuploid. In the aneuploid cases, the serum AFP level was found to be higher and stage more advanced. We also found that patients with aneuploid tumors had a poorer prognosis than those with diploid tumors, this fact uncovered by means of a Cox's proportional hazard model. In conclusion, the ploidy pattern of the nuclear DNA may serve as a useful prognostic marker for a hepatocellular carcinoma.

A 31-year-old man, suffering from Behçet disease, was admitted to our hospital because of a palpable mass in the right hypochondrium. On testing, laboratory data showed an abnormal liver function, positive HBs antigens, and a high AFP level. An abdominal CT and a SCAG revealed large tumors in the liver. The patient died of hepatic failure 6 months after the first admission and an autopsy was performed. At autopsy, hepatocellular carcinomas were found to occupy most of the entire liver. Histologically, the residual liver showed no remarkable changes, such as liver cirrhosis or chronic hepatitis. To date, few cases of Behçet disease complicating a malignant neoplasma have been reported. The possible relationship between Behçet disease and the occurrence of malignant tumors is described with a review of the literature.