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Key Clinical Message Autologous formalin-fixed tumor vaccine (AFTV) suppressed re-recurrence for more than 32 months of multiple-recurrent hepatocellular carcinoma based on hepatitis C virus-induced liver cirrhosis in a case with previous recurrence interval, 51-, 28-, 12-, and 4-months. We detected glypican-3-specific cytotoxic T lymphocytes in the peripheral blood at 12 months after AFTV.

The sudden change in the dietary habits of the Japanese population towards a European/American-style diet since the 1960s is thought to be responsible for the recent increase in the incidence of inflammatory bowel disease (IBD) in Japan. Dietary fatty acid intake influences the fatty acid profiles of vital cell membranes, which might be a source of inflammatory mediators. We investigated the fatty acid composition of the erythrocyte membrane in 90 healthy Japanese and 43 initial-onset IBD patients (ulcerative colitis, UC: 25; Crohn’s disease, CD: 18) who had not undergone any dietary intervention to examine the role fatty acids play in the onset of IBD. The erythrocyte membrane n-3/n-6 ratio of the initial-onset IBD patients was 0.42 ± 0.13, which was not significantly different from that of the healthy Japanese subjects (0.41 ± 0.13). However, the CD patients displayed a significantly lower mean percentage weight (MPW) of linoleic acid (LA) than the healthy subjects (8.25 ± 1.75 vs. 9.90 ± 1.29; p

Background Standard-dose ribavirin is crucial for the standard-of-care treatment of chronic hepatitis C virus (HCV) infection. Equilibrative nucleoside transporter 1 (ENT1), encoded by SLC29A1 gene, is the main transporter that imports ribavirin into human hepatocytes. Aims: To determine whether single nucleotide polymorphisms (SNPs) at the SLC29A1 gene could influence the probability of treatment response compared with other baseline and host genetic factors. Methods A total of 526 East Asian patients monoinfected with HCV genotype 1b who had received pegylated interferon alpha plus ribavirin therapy were enrolled in this study. They were assigned randomly to the derivation and confirmatory groups. SNPs related to the IL28B,ITPA and SLC29A1 genes were genotyped using real-time detection polymerase chain reaction. Factors associated with sustained virological response (SVR) were analysed using multiple logistic regression analysis. Results Multivariate analysis for the derivation group identified six baseline variables significantly and independently associated with SVR: age [P = 0.023, odds ratio (OR) = 0.97], gender (P = 0.0047, OR = 2.25), platelet count (P = 0.00017, OR = 1.11), viral load (P = 0.00026, OR = 0.54), IL28B SNP rs12979860 (P = 1.09 × 10−7, OR = 8.68) and SLC29A1 SNP rs6932345 (P = 0.030, OR = 1.85). Using the model constructed by these independent variables, positive and negative predictive values and predictive accuracy were 73.3, 70.1 and 71.9% respectively. For the confirmatory group, they were 71.4, 84.6 and 75.3% respectively. The SLC29A1 and IL28B SNPs were also significantly associated with rapid virological response. Conclusions The SNP at the major ribavirin transporter ENT1 gene SLC29A1 was one of significantly independent factors influencing treatment response, although the impact on the prediction was small.

Background: N-3 polyunsaturated fatty acids (PUFA) are considered important pharmaconutrients for modulating mucosal immunity and therapeutic responses in patients with inflammatory bowel disease (IBD). We investigated the influence of diet therapy involving the use of an “n-3 PUFA food exchange table” (n-3DP) on the fatty acid composition of the erythrocyte membranes of IBD patients and its remission-maintaining effects. Methods: We analyzed the fatty acid composition of the erythrocyte membrane before and after n-3DP intervention in 20 initial-onset IBD patients who had not undergone any dietary intervention. We then analyzed it again and evaluated disease activity after 12–18 months intervention in 230 IBD patients (168 ulcerative colitis, 62 Crohn's disease; follow-up group) in whom n-3DP was introduced after remission had been achieved. The follow-up group was divided into remission and relapse groups. Results: In the 20 initial-onset patients, the mean n-3/n-6 ratio significantly increased after intervention (0.41 ± 0.16 versus 0.70 ± 0.20; P < 0.001). In the follow-up group the ratio in the remission group (n = 145) was significantly higher than that in the relapse group (n = 85) (0.65 ± 0.28 versus 0.53 ± 0.18; P < 0.001). The ratio significantly decreased in those who suffered a relapse after the beginning of treatment (P < 0.01). Conclusions: N-3DP significantly increased the erythrocyte membrane n-3/n-6 ratio in IBD patients, and this ratio was significantly higher in the remission group, suggesting that n-3DP alters the fatty acid composition of the cell membrane and influences clinical activity in IBD patients. (Inflamm Bowel Dis 2010)

A 68-year-old man visited our department because of diarrhea and bloody stools. Colonoscopy revealed diverticula scattered in the sigmoid colon with localized mucosal edema and reddening. The mucosa became somewhat rough 9 months later, and had an erosive, ulcerative colitis (UC)-like appearance after a further 6 months, with these changes extending to the rectum. These findings led to a diagnosis of diverticular colitis (DC) with UC-like changes. The condition was refractory to treatment including drug therapy and was thus surgically treated. No cases of DC have been reported in Japan, and a refractory case of DC with progressive UC-like changes extending to the rectum is rare even in Europe and the USA.

We report a Helicobacter pylori-negative patient with multiple gastric antral ulcers of unknown etiology and without a history of taking non-steroidal anti-inflammatory drugs (NSAIDs). The patient was a 68-year-old woman, and her serum gastrin and pepsinogen levels were within normal limits. The antral ulcers were refractory to treatment with a proton pump inhibitor (PPI) or an H2 receptor antagonist alone. However, since nocturnal gastric acid breakthrough was observed, both drugs were given in combination, which resulted in the healing of the ulcers.

Background/Aims: To assess the effect of lactoferrin on oxidative liver damage and its mechanism, we used Long-Evans Cinnamon (LEC) rats that spontaneously develop fulminant-like hepatitis and lethal hepatic failure. Methods: Four-week-old female LEC rats were divided into the untreated and treated groups. The latter was fed bovine lactoferrin at 2% mixed with conventional diet. Results: The cumulative survival rates were 75.0% vs. 100% at 14 weeks, 37.5% vs. 91.7% at 15 weeks, and 12.5% vs. 91.7% at 16 weeks, respectively, for untreated and treated rats (P = 0.0008). The 8-OHdG levels in liver mitochondrial DNA and malondialdehyde in plasma and liver tissues were significantly lower in treated than untreated rats (P < 0.001, =0.017 and 0.034, respectively). Mitochondrial DNA mutations were more common in untreated rats. OGG1 mRNA and protein expression levels were significantly lower in untreated than treated rats (P = 0.003 and 0.007, respectively). Hypermethylation of the second CpG island located upstream of OGG1 gene was observed in untreated rats. Conclusions: Our findings indicated that lactoferrin inhibits oxidative liver damage in LEC rats. Lactoferrin could be potentially useful for the treatment of oxidative stress-induced liver diseases. 2007 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

症例は18歳女性．生来健康だったが，ウコン，女性ホルモン剤を内服していたところ黄疸，肝障害を認めた．肝生検では形質細胞浸潤，ロゼット形成を伴う肝硬変像を呈し，実質には著明な出血壊死を認めた．腹部CTでは脾腫，胃腎シャントを認め，内視鏡では胃・食道静脈瘤を認めた．自己免疫性肝炎（AIH）の国際診断基準スコアは治療前で+15であり，背景肝としてAIHが考えられた．大循環シャントが形成されており，ある期間をかけてAIHから肝硬変に進展した後に急性肝障害が加わったと推測された．

長期にラミブジン (LAM) 投与がなされたB型慢性肝炎症例を対象として, LAM耐性株の出現に伴う肝炎再燃の予測および投与中止時期決定のため, B型肝炎ウイルス (HBV) DNAの推移を高感度定量法を用いて検討した. HBV DNA陽性のB型慢性活動性肝炎で, 24カ月以上LAM投与が継続された8症例 (35～59歳, 男性が7例, F3が4例, HBe抗原陽性が3例, ゲノタイプは全例C型, コアプロモーターは全例変異型) を対象とした. HBV DNA定量法としてTMA-HPA法, アンプリコアHBVモニター法に加え, 超高感度検出系のHBV RTD-PCR direct (DIRECT) 法を導入した. 検討の結果, 4例において長期経過後にDNA量の再上昇およびYMDD変異株の出現が認められたが, 4例ともLAM投与経過中にDNA量の軽度上昇がみられていた. 1例においては経過中のDNA量の上昇をDIRECT法においてのみ捉えられており, LAM投与症例においてHBV DNAの推移を観察していく上でDIRECT法の有用性が示唆された.

Human metastatic colorectal carcinomas (CRCAs) express carcinoembryonic antigen (CEA) and/or MUC1 tumor-associated antigens as potential targets for the induction of active specific immunity. In the present study, freshly isolated metastatic CRCA cells were successfully fused with immature autologous human monocyte-derived dendritic cells (DCs). The created heterokaryons (DC/CRCA) coexpress the CRCA-derived CEA and MUC1 antigens and DC-derived MHC class II and costimulatory molecules. The fusion cells were functional in stimulating the proliferation of autologous T cells. In addition, both CD4+ and CD8+ T cells were activated by fusion cells, as demonstrated by the production of high levels of IFN-γ. More importantly, coculture of fusion cells with patient-derived peripheral blood mononuclear cells (PBMCs) resulted in the induction of antigen-specific cytotoxic T lymphocytes (CTLs). CTLs were effective at lysis of not only autologous CRCA cells but also the CEA and/or MUC1-positive and HLA partially matched target cells. Antigen-specific CTL responses were confirmed by tetrameric analysis. Coculture of PBMCs with fusion cells resulted in increased frequency of CEA- and MUC1-specific CTLs simultaneously. Taken together, these results indicate that freshly isolated human metastatic CRCA cells expressing the CEA and/or MUC1 may represent a potential partner for the creation of DC/tumor fusion cells targeting induction of antigen-specific CTL responses. Our report demonstrates the simultaneous induction of CRCA-specific CTL responses restricted by HLA-A2 and -A24. © 2005 Wiley-Liss, Inc.

症例は60歳女性. 黄疸を主訴に入院. 肝機能障害を認め, 肝炎ウイルスマーカー陰性で, 飲酒歴, 薬物歴なく, 抗核抗体陽性等より自己免疫性肝炎 (autoimmune hepatitis, AIH) と診断した. 肝組織所見は慢性活動性肝炎で, 肝機能障害はプレドニゾロン投与により改善し, 治療後のAIHスコアーは24点で確診例であった. さらに橋本病, 特発性副甲状腺機能低下症, 多発性筋炎の合併を認め, 多腺性自己免疫症候群 (autoimmune polyglandular syndrome, APS) を合併したAIHと診断した. AIHとAPSの合併例の報告は, わが国では少なく貴重な症例と考えられた.

Background and Objectives Surgical resection of hepatocellular carcinoma (HCC) is not always regarded as the first choice of treatment, because most HCCs develop in cirrhotic liver. It becomes adaptation of minimally invasive treatments for HCC. In animal experiments, we previously reported that our newly developed neodymium:yttrium aluminum garnet (Nd:YAG) laser system could ablate liver tissue in short periods. Study Design/Patients and Methods Six HCC cases (mean diameter; 16.3 ± 3.50 mm) were enrolled. The Nd:YAG laser generator with a wavelength of 1,064 nm at 10 W of power emitted the laser in a forward fashion and in all patients the laser beam safely irradiated the target lesion. Results There was no recurrence of HCC in the laser-ablated area in six patients for duration of 21.8± 4.35 months. A local recurrence was found in only one patient. Conclusions This study showed the clinical usefulness of laser ablation in the treatment of HCC. Lasers Surg. Med. 35:135–139, 2004. © 2004 Wiley-Liss, Inc.

Aims: A highly reproducible and sensitive hepatitis B virus real-time detection direct (HBV RTD-direct) test using DNA extraction by magnetic beads coated with polyclonal anti-HBsAg, followed by the real-time detection polymerase chain reaction (PCR) method, was developed for the detection of HBV DNA. Methods: The HBV DNA could be extracted from the HBsAg positive viral particles without resulting in viral DNA fragmentation. The HBV RTD-direct test was validated using a serial dilution panel of the WHO standard HBV DNA 97/746 I. Results: The test had a dynamic range of 0.7–8.0 log10 international units (IU) per mL and the results were shown to be comparable to those obtained with two commercially available tests: the HBV DNA transcription-mediated amplification-hybridization protection assay and the Amplicor HBV Monitor test. In addition, the HBV RTD-direct test, based on magnetic extraction, successfully eliminated PCR inhibitors in clinical specimens. Conclusion: We conclude that the HBV RTD-direct test is an excellent alternative for monitoring patients undergoing antiviral treatment or for screening various clinical specimens.

It has been reported that the local thermotherapy is useful in treatment of hepatocelluar carcinoma complicated with severe liver cirrhosis (LC). We studied the effect of laser beam generated by a newly developed Nd-YAG laser system on liver tissue of piglet. The system was composed of their quartz bare fiber with a cone-shaped tip. After liver was exposed by incision of abdomen under general anesthesia, the fiber was inserted into liver tissue and then the laser beam was generated. The power, duration and frequency of irradiation were varied. The coagulated area was inspected measured and examined histologically. The system produced an oval-shaped coagulated area in front of the needle tip. Furthermore, the volume of tissue coagulated was correlated with the total output of laser, enabling us to estimate the coagulated volume based on the laser output applied. Our findings indicated that Nd-YAG laser-induced thermotherapy would be successfully applied for the clinical treatment of HCC.

The patient was a 35-year-old man who was observed after bone marrow transplantation for acute lymphocytic leukemia. Polyps were found by colonoscopy performed after a positive fecal occult blood test, and the patient was admitted for polypectomy. There were three polyps, which were all reddened and pedunculated and were, respectively, located in the transverse, descending, and sigmoid colons. Polypectomy was performed, and all lesions were histopathologically diagnosed to be inflammatory myoglandular polyps. Inflammatory myoglandular polyps have been reported to occur solitarily only, and this is the first report of multiple occurrence.

症例は51歳女性, 看護婦. 主訴は全身倦怠感. 平成8年3月22日, C型慢性肝炎患者に使用した注射針にて左足背部を刺傷. 同年4月5日頃より, 全身倦怠感出現し, 4月13日の血液検査で肝機能障害を指摘され入院となった. 入院時の肝炎ウイルスマーカーはHBs抗体を除き全て陰性であったが, DNA probe法によるHCV-RNAの定量では40Meq/ml以上と高値を呈していた. そのため, インターフェロン (IFN) -βの投与を施行し, 効果が認められた. しかし, 終了後19日目に再燃がみられ, IFN-α2bの追加投与を行い著効が得られた. また, 汚染血と被汚染血中のHCV-RNAのgenotypeは1b型で一致していた. さらに, direct sequence法によるNS5A領域内の40アミノ酸の解析でも, 両者ともに2カ所に同一の変異がみられ一致していた.

Ten patients who suffered from acute hepatitis with various clinical forms due to hepatitis B virus (HBV) were studied. HBV variants with a mutation in the precore region were dominant in two patients with fulminant hepatitis and in a patient with the most severe acute hepatitis. However, these mutant viruses were not detected in a patient who had the fulminant form of acute HBV infection on chronic liver damage or in most patients who had severe acute hepatitis. Furthermore, mutant viruses were also not detected in a patient with complicating myopathy and in one who had an atypical clinical course with three transaminase peaks. These results suggest that precore mutants may be involved in the pathogenesis of some cases of severe acute hepatitis, the same as for fulminant hepatitis, but not in other clinical forms of acute hepatitis.

Three patients who were carriers of hepatitis B virus (HBV) and had hematologic malignancies, experienced fulminant hepatic failure after withdrawal of chemotherapy. Before treatment, each patient had inactive HBV infection with undetectable viral DNA polymerase; two patients were negative for hepatitis B e antigen. After chemotherapy, DNA polymerase increased and HBV variants with mutations in the precore region prevailed in their sera. These results implicate precore mutants thriving after chemotherapy and restored immune responses of patients in the pathogenesis of severe hepatic failure.

A patient was a 46-year-old man. Multiple lung tumors had been pointed out on a medical examination at age 24. He came to our hospital for further examination. Multiple liver and lung tumors were found out, and epithelioid hemangioendothelioma (EHE) derived from the liver was diagnosed by biopsy. At first we gave recombinant interleukin-2 (rIL-2) by intra-arterial and local injection and then continued it by intramuscular injection for 22 years as maintenance therapy. The tumors have regressed, with partial necrosis. EHE is a rare tumor, but we do not have a standard antitumor therapy except surgical resection. This case suggests that rIL-2 may become a new therapy for EHE. We think that the report of the long-term survival of a case of EHE in which rIL-2 treatment was effective is extremely valuable.

To construct formulae for predicting the likelihood of ribavirin-induced anemia in pegylated interferon α plus ribavirin for chronic hepatitis C.Five hundred and sixty-one Japanese patients with hepatitis C virus genotype 1b who had received combination treatment were enrolled and assigned randomly to the derivation and confirmatory groups. Single nucleotide polymorphisms at or nearby ITPA were genotyped by real-time detection polymerase chain reaction. Factors influencing significant anemia (hemoglobin concentration10.0 g/dL at week 4 of treatment) and significant hemoglobin decline (declining concentrations3.0 g/dL at week 4) were analyzed using multiple regression analyses. Prediction formulae were constructed by significantly independent factors.Multivariate analysis for the derivation group identified four independent factors associated with significant hemoglobin decline: hemoglobin decline at week 2 [P = 3.29 × 10(-17), odds ratio (OR) = 7.54 (g/dL)], estimated glomerular filtration rate [P = 2.16 × 10(-4), OR = 0.962 (mL/min/1.73 m(2))], rs1127354 (P = 5.75 × 10(-4), OR = 10.94) and baseline hemoglobin [P = 7.86 × 10(-4), OR = 1.50 (g/dL)]. Using the model constructed by these factors, positive and negative predictive values and predictive accuracy were 79.8%, 88.8% and 86.2%, respectively. For the confirmatory group, they were 83.3%, 91.0% and 88.3%. These factors were closely correlated with significant anemia. However, the model could not be constructed, because no patients with rs1127354 minor genotype CA/AA had significant anemia.Reliable formulae for predicting the likelihood of ribavirin-induced anemia were constructed. Such modeling may be useful in developing individual tailoring and optimization of ribavirin dosage.

The aims of this study were to assess the long-term efficacy of lamivudine (LAM) plus adefovir dipivoxil (ADV) combination therapy in patients with chronic hepatitis B resistant to LAM, to identify predictive factors of complete viral response (HBV-DNA

We investigated the immunological factors concerning the backgrounds of non- and low-responders who could not respond well to the hepatitis B (HB) vaccine. We injected 10 micrograms of the recombinant HB vaccine to the medical staffs of our hospital intramuscularly three times, 199 subjects of whom could receive the full course of immunization with the HB surface (HBs) antigen. We found that 14 subjects were non-responders whose titer of HBs antibody was under the 1.9 cut off index (C.I.) examined by radioimmunoassay (RIA) and 47 ones were low-responders whose titers were between 2.0 to 9.9 C.I. and the frequency of non- and low-responders was higher in males after the full course of HB vaccination. We chose 46 subjects and divided them into 4 groups according to the titer of HBs antibody at 8 and 28 weeks. We compared those groups to each other according to the amounts of total protein, gamma-globulin, IgG, IgA and IgM, numbers of peripheral white blood cells and lymphocytes, and percentages of peripheral lymphocyte and subsets of T cell including the examination by two-color flow cytometry using monoclonal antibodies. However we could not get any significant difference in any of those immunological factors by T assay. From these findings we suggest that the response to the HB vaccine does not depend on the quantity of the immunological factors before vaccination but on specific reactivity to HBs antigen after vaccination.

There are cases of hepatitis involving occult hepatitis B virus (HBV) infection in which, even though the HB surface antigen (HBsAg) is negative, HBV-DNA is detected by a polymerase chain reaction (PCR). We conducted a sequence analysis of the entire HBV region in a case of non-B non-C chronic hepatitis in a 46-year-old female. A diagnosis of non-B non-C chronic hepatitis was made. Although HBV markers, such as HBs antibody (anti-HBs), anti-HBc, HBeAg and anti-HBe, were negative, HBV-DNA was positive. Nested PCR was performed to amplify the precore region of HBV-DNA and all remaining regions by long nested PCR. Sequence analysis of the two obtained bands was conducted by direct sequencing. Compared with the control strains, the ATG (Methionine) start codon in the X region had mutated to GTG (Valine). It is assumed that a mutation at the start codon in the X region may be the reason why HBV markers are negative in some cases of hepatitis that involve occult HBV infection.

Objective The aim of this study was to investigate the outcome of overlap/switch to adefovir dipivoxil (ADV) monotherapy for chronic hepatitis B (CHB) patients with lamivudine (LAM)-resistant HBV, who responded to LAM plus ADV combination therapy. Methods In 29 of 35 LAM-resistant CHB patients, serum HBV-DNA levels decreased to

A 57-year-old man developed acute hepatitis B virus (AHB), caused by HBV genotype Ae. Lamivudine (LAM) therapy was started at 8 months after the disease onset, because the infection was persistent, but not self-limited. Despite LAM therapy, the hepatitis became chronic. Further, virological breakthrough developed due to the emergence of LAM-resistant YMDD mutants at 11 months after LAM therapy. Adefovir dipivoxil (ADV) was combined with LAM against breakthrough hepatitis at 28 months after LAM therapy. Sequential genetic analysis revealed that rtL217R, a mutation potentially diminishing the ADV efficacy, was detected before and after the combination therapy. During the follow-up period, the patient unexpectedly turned out coinfected with human immunodeficiency virus (HIV) by measuring anti-HIV-1 antibody. At that time, LAM-resistant HIV mutation, M184V, had been already detected. We switched from the combination therapy with LAM plus ADV to highly active antiretroviral therapy (HAART), which included tenofovir disoproxil fumarate. HAART drastically improved LAM-resistant viremia and breakthrough hepatitis as well as HIV viremia and CD4 counts. Even in Japan, HBV genotype and HIV coinfection should be determined early in the treatment of AHB, and early induction of nucleotide analogs should be taken into consideration, because the proportion of AHB patients with HBV genotype A and the number of patients horizontally coinfected with HBV and HIV are increasing.

Upper gastrointestinal endoscopy of a 25-year-old man with heartburn revealed an elevated lesion in the esophagogastric junction (EGJ). Piecemeal endoscopic mucosal resection (EMR) followed by histopathological examination led to a diagnosis of inflammatory fibroid polyp (IFP). After EMR, the heartburn persisted despite giving a proton pump inhibitor (PPI), and the residual lesion gradually enlarged and a transverse mucosal break developed on the esophageal side of it. However, the combined administration of the PPI and an H2 receptor antagonist reduced the heartburn, and led to endoscopic regression of the lesion and disappearance of the transverse mucosal break. IFP of the esophagogastric junction is extremely rare, and this case is interesting in that potent inhibition of gastric acid secretion resulted in the regression of the lesion.

Cancer gene therapy requires a safe and effective gene delivery system. Polymer- and lipid-coated magnetic nanocrystals have been used to deliver silencing RNA, but synthesizing these magnetic vectors is difficult. Here, we show that a new nanoparticle formulation can be magnetically guided to deliver and silence genes in cells and tumours in mice. This formulation, termed LipoMag, consists of an oleic acid-coated magnetic nanocrystal core and a cationic lipid shell. When compared with the commercially available PolyMag formulation, LipoMag displayed more efficient gene silencing in 9 of 13 cell lines, and better anti-tumour effects when systemically administered to mice bearing gastric tumours. By delivering an optimized sequence of a silencing RNA that targets the epidermal growth factor receptor of tumour vessels, the intended therapeutic benefit was achieved with no evident adverse immune reaction or untoward side effects.

AIM: To assess the efficacy and advantages of 4-wk pegylated interferon α-2a (peg-IFN-α2a) monotherapy for chronic hepatitis C patients with strong predictors of sustained virologic response (SVR). METHODS: Patients (n = 33) with genotype 2 and low viral load (< 100 KIU/mL), who became HCV RNA negative after 1 wk of IFN treatment, were randomly allocated to receive a 4- or 12-wk treatment course at a ratio of 2:1, respectively, with a subsequent 24-wk follow-up period. Peg-IFN-α2a was administered subcutaneously at a dose of 180 μg or 90 μg once weekly. SVR was defined as absence of serum HCV RNA at the end of the follow-up period. RESULTS: All patients completed the treatment schedule, and more than half were symptom-free during the treatment. In the 4-wk treatment group, 20 of 22 (91%) patients achieved SVR. Two patients relapsed, but achieved SVR following re-treatment with peg-IFN-α2a alone. In the 12-wk treatment group, 11 of 11 (100%) patients attained SVR. CONCLUSION: Our results show that a 4-wk course of peg-IFN-α2a monotherapy can achieve a high SVR rate in “IFN-sensitive” patients, without negatively affecting outcome.

We encountered a case of Cronkhite-Canada syndrome in which contrast radiologic examinations of the upper and lower digestive tract were performed immediately before and after the development of the clinical symptoms. These contrast radiologic images showed mainly mucosal coarseness and no polyposis of the stomach and colon. The endoscopy, performed 3 months later from the development of the clinical symptoms, revealed polyposis of the stomach and colon. So we recognized that the clinical symptoms developed before appearance of the polyposis of the digestive tract and the polyposis progressed rapidly.

Two young man patients with refractory post-bulbar duodenal ulcer (post-bulbar ulcer) were encountered. They had a single punched-out ulcer in the absence of an underlying disease. Patient 1 was Helicobacter pylori (Hp)-positive, and did not respond to Hp eradication therapy. The ulcer scarred after the long-term administration of a proton pump inhibitor (PPI), but recurred after a reduction in the dose. Patient 2 was Hp-negative. His ulcer did not scar even after long-term PPI administration, but it formed a fistula into the gallbladder, and the fistula was surgically closed. In both patients, laboratory and imaging studies excluded Zollinger-Ellison syndrome, but suggested a hyperacidic tendency. Unlike duodenal bulb ulcer (bulbar ulcer), the post-bulbar ulcer in Patient 1 did not heal with Hp eradication therapy, suggesting that post-bulbar ulcer differs etiologically from bulbar ulcer. We speculate that the possible causes of the refractoriness to treatment in both patients were ulcer penetration, callosity formation, and insufficient inhibition of gastric acid secretion due to the impaired passage of PPI into the deep portion of the duodenum as a result of luminal narrowing.

A 46-year-old man was admitted because of ileus. He had undergone an operation for lung carcinoma (stage IA) 8 years previously in another hospital. Because small bowel enema study showed widespread stricture of the ileum, we performed an operation. During the operation we diagnosed metastatic small bowel carcinoma. Because the resected sample of the small bowel carcinoma was similar to the lung carcinoma pathologically and detailed examination after the operation showed no other neoplasm, we considered this case to be small bowel metastasis of the lung carcinoma resected 8 years previously.

A 50-year-old man with type B liver cirrohosis was admitted with jaundice and ascites. He had undergone an operation for esophageal variceal rupture at another hospital. Abdominal CT scan and ultrasonography showed cystic dilatation of the extrahepatic portal vein, and Doppler ultrasonography showed it to be a portal vein aneurysm. After admission, jaundice progressed, and not only liver failure but also biliary tract obstruction was suspected as its etiology. Therefore, endoscopic retrograde cholangiography was performed, and it showed a remarkably bent extrahepatic bile duct thought to be caused by extrinsic compression. By combining the finding of endoscopic ultrasonography, we considered that the portal vein aneurysm had displaced the bile duct. We suspected that it also caused cholestasis and cholangitis.

The patient was a 63-year-old woman with attacks of fever and abdominal pain, starting from the age of 53 years and recurring every month. Despite various examinations at another hospital, the etiology remained unclear. She was under symptomatic treatment, and was referred to our department for further evaluation. Although she had onset in middle age, the clinical symptoms and examination findings suggested familial Mediterranean fever, and administration of colchitine inhibited the attacks completely. Therefore, the patient was diagnosed as having the disease. We were not able to analyze the entire MEFV gene, but detected only a heterozygous M694I mutation. Amyloidosis did not develop as a complication. The disease is rare in Japan, and its onset in the fifties is extremely rare in the world.

The aim of antitumor immunotherapy is to induce CTL responses against autologous tumors. Previous work has shown that fusion of human dendritic cells and autologous tumor cells induce CTL responses against autologous tumor cells in vitro. However, in the clinical setting of patients with colorectal carcinoma, a major difficulty is the preparation of sufficient amounts of autologous tumor cells. In the present study, autologous dendritic cells from patients with colorectal carcinoma were fused to allogeneic colorectal tumor cell line, COLM-6 (HLA-A2−/HLA-24−), carcinoembryonic antigen (CEA)+, and MUC1+ as an alternative strategy to deliver shared colorectal carcinoma antigens to dendritic cells. Stimulation of autologous T cells by the fusion cells generated with autologous dendritic cells (HLA-A2+ and/or HLA-A24+) and allogeneic COLM-6 resulted in MHC class I– and MHC class II–restricted proliferation of CD4+ and CD8+ T cells, high levels of IFN-γ production in both CD4+ and CD8+ T cells, and the simultaneous induction of CEA- and MUC1-specific CTL responses restricted by HLA-A2 and/or HLA-A24. Finally, CTL induced by dendritic cell/allogeneic COLM-6 fusion cells were able to kill autologous colorectal carcinoma by HLA-A2- and/or HLA-A24-restricted mechanisms. The demonstration of CTL activity against shared tumor-associated antigens using an allogeneic tumor cell line, COLM-6, provides that the presence of alloantigens does not prevent the development of CTL with activity against autologous colorectal carcinoma cells. The fusion of allogeneic colorectal carcinoma cell line and autologous dendritic cells could have potential applicability to the field of antitumor immunotherapy through the cross-priming against shared tumor antigens and provides a platform for adoptive immunotherapy.

We evaluated the effect of a "tailor-made" chemo-gene therapy in scirrhous gastric cancer (SGC)-bearing nude mice. For this tailor-made approach, we first selected gefitinib (epidermal growth factor receptor-tyrosine kinase inhibitor)-sensitive SGC cell lines, and 5/8 cell lines demonstrated various degrees of gefitinib-sensitivity. In the highly gefitinib-sensitive NUGC-4, the biological response to NK4 (HGF antagonist/angiogenesis inhibitor) was examined. Subsequently, the composition of an NK4-expressing ternary complex (cationic lipid/nucleic acid/HMG-1, 2 protein) was optimized for maximum transfection activity in NUGC-4. Finally, mice were peritoneally coinoculated with NUGC-4 and scirrhous-associated gastric fibroblasts, NF22, on day 0. Animal models were orally administrated gefitinib (50 mg/kg/day, on days 7-28), and peritoneally NK4-expressing ternary complex (on days 14, 21 and 28). NK4-expression suppressed the gefitinib-resistance induced by the interaction between fibroblasts and SGC, and eventually, this tailor-made combination synergistically decelerated the disease progression by inhibiting proliferative, angiogenic and antiapoptotic effects in tumor tissues. On day 28, both the hemoglobin concentration (g/dl) (control (n = 8), 11.9; treated (n = 8), 17.3; p = 0.0014) and the numbers of mice in good condition (control, 2; treated, 8; p = 0.0012) were significantly greater, and the abdominal girth (mm) (control, 81.1; treated, 70.3; p = 0.0036) was significantly reduced. The median points of bloody ascite-free survival time (days) (control, 22; treated, 44; p < 0.0001) and time to euthanasia (days) (control, 36.5; treated, 56; p < 0.0001) were also significantly prolonged. This combination is a potentially useful approach to the treatment of peritoneal gefitinib-sensitive SGC dissemination.

To develop a new sensitive and inexpensive hepatitis C virus (HCV) combination test (HCV Guideline test) that enables the determination of HCV genotypes 1, 2 and 3, and simultaneous determination of HCV viral load using commercial Amplicor GT HCV MONITOR test v2.0 (microwell version).The HCV Guideline test used the PCR product generated in commercial Amplicor GT HCV Monitor test v2.0 for viral load measurement using microwell plate version of Amplicor HCV Monitor and also captured on separate plates containing capture probes and competitive oligonucleotide probes specific for HCV genotypes 1, 2 and 3, The HCV genotype was subsequently determined using the biotin-labeled PCR product and five biotin-labeled HCV-specific probes.The sensitivity of the HCV Guideline test was 0.5 KIU/mL. Specificity of the HCV Guideline test was confirmed by direct sequencing of HCV core region and molecular evolutionary analyses based on a panel of 31 samples. The comparison of the HCV Guideline test and an in-house HCV core genotyping assay using 252 samples from chronic hepatitis C patients indicated concordant results for 97.2% of samples (59.5% genotype 1, 33.7% genotype 2, 6.0% genotype 3, and 0.8% mixed genotypes). Similarly, the HCV Guideline test showed concordance with a serological test, and the serological test failed to assign any serotype in 12.7% of the samples, indicating a better sensitivity of the HCV Guideline test.Clinically, both viral load and genotypes (1, 2 and 3) have been found to be major predictors of antiviral therapy outcome regarding chronic hepatitis C based on guidelines and they are, in normal circumstances, performed as separate stand-alone assays. The HCV Guideline test is a useful method for screening large cohorts in a routine clinical setting for determining the treatment regimen and for predicting the outcome of antiviral therapy of chronic hepatitis C.

Changes of titers of acquired hepatitis B surface (HBs) antibodies against HB vaccine were investigated by measuring them again after a long lapse of time. Ten micrograms of the recombinant HB vaccine was intramuscularly injected respectively to the staff of the authors' hospital three times. Four weeks after a full course of the vaccination 185 persons could acquire antibodies, whose titers were 2.0 or more in cut off index (C.I.) by radioimmunoassay (RIA). Of these members titers of antibodies of 48 subjects could be remeasured for the first time 38 months after the measurement of the titers in the 4th week after a full course of the vaccination. Four weeks after the last vaccination 7 persons were high responders whose titers of antibodies were 50 or more in C.I. 29 were medium responders with their titers from 49 to 10, and 12 were low responders having titers of less than 10. However, 38 months after the course the titers of those responders decreased so much that nobody remained highly responders, 22 were low responders, and the remaining 22 turned to be negative again with titers less than 2.0. Supposing that the titer of antibody enough to protect the infection of HB virus is 10 or more in C.I., 32 of 36 persons needed booster shots 38 months later because their titers dwindled down to less than 10.(ABSTRACT TRUNCATED AT 250 WORDS)

We conducted a prospective randomized trial to evaluate the efficacy of Lipiodol in intrahepatic arterial infusion chemotherapy for patients with hepatocellular carcinoma (HCC). A total of 38 patients with unresectable HCCs and underlying cirrhosis were entered in this trial, and 36 of them were evaluable. Every 4 weeks, 17 patients received 70 mg of 4'-epidoxorubicin (epirubicin) alone (group A), whereas 19 patients received a Lipiodol emulsion containing the same dose of epirubicin (group B) through the hepatic artery. A tumor response (CR+PR) was observed in 12% of group A patients and in 42% of group B patients. The group B patients showed a significantly higher response rate than the group A patients. There was a tendency for an increased duration of survival (P = 0.09) in the group B patients. These results suggested that the infusion of the Lipiodol emulsion with epirubicin was more effective than epirubicin alone for the treatment of these patients with HCC.