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Temporary fully covered self-expandable metal stent (FCSEMS) placement is performed for benign choledochojejunal anastomotic stenosis (bCJS). However, recurrence may develop after stricture resolution. We investigated endoscopic biliary stenting using FCSEMS for bCJS.Sixteen bCJS patients with FCSEMS placement were retrospectively analyzed. FCSEMS was removed endoscopically after 2 months. Technical success, stricture resolution, recurrence, and adverse events were evaluated.The technical success rate for FCSEMS placement was 94% (15/16). Biliary stones were detected and extracted in four patients. FCSEMS removal was successfully performed on 14 patients, excluding one with stent migration. At FCSEMS removal, stricture resolution was noted in 14 patients; however, four had anastomotic ulcers. The median follow-up was 319 days. Three patients with a history of repeated plastic stent placement had no recurrence. Four out of 15 patients (27%) had recurrence, and three had no recurrence after additional interventions. Biliary stones before first FCSEMS placement (P = .003) or anastomotic ulcers at FCSEMS removal (P = .018) were associated with recurrence.Although FCSEMS placement was useful for stricture resolution, recurrence was detected in patients with biliary stones before first FCSEMS placement or anastomotic ulcers at FCSEMS removal. Anastomotic ulcers are a risk factor for recurrence and only detected by endoscopy.

Background We aimed to determine the optimal approach with endoscopic biliary drainage (EBD) and corticosteroid (CS) for the treatment of IgG4-related sclerosing cholangitis (ISC). Methods To evaluate the safety of EBD for treatment of biliary stricture caused by ISC, we assessed the risk of stent dislodgement and sought to determine the most appropriate time for stent removal. We also assessed the safety of treatment with CS alone for patients with obstructive jaundice, and the rate of and risk factors for biliary tract complications. Results Sixty-nine patients with ISC treated with CS were enrolled. Twenty-eight patients (40.6%) were treated with EBD for biliary stricture before CS initiation. Intentional stent removal was performed in thirteen (46.4%) after confirming CS-induced improvement. Eleven of thirteen patients (84.6%) underwent stent removal within 1 month after CS initiation and all their stent removals were safely carried out without early (within two weeks) recurrence of obstructive jaundice. Ten of twenty-eight patients (35.7%) experienced spontaneous stent dislodgement after CS initiation, and seven (70%) of them developed stent dislodgement two weeks to two months after CS initiation. Among forty-one patients treated with CS alone without EBD, 10 patients had obstructive jaundice at the time of CS initiation and all of them achieved clinical improvement without biliary tract infection. During the follow-up, three patients (4.3%), all of whom had undergone EBD, developed bile-duct stones, while none of those treated with CS alone developed bile-duct stones (p = 0.032). Long-term biliary stenting was a risk factor for bile-duct stones. Conclusions Biliary stent removal should be carried out within 2 weeks after CS initiation if biliary stricture improves to prevent stent dislodgement. Obstructive jaundice can be treated safely with CS alone in patients without infection. Clinicians should be aware of the possibility of bile-duct stones in patients treated with EBD.

We aimed to test the hypothesis that selenoprotein P (SELENOP), a hepatokine involved in the development of both insulin resistance and impaired insulin production in mice, is related to future onset of hyperglycemia in humans. 76 healthy non-pregnant human subjects without diabetes underwent oral glucose tolerance test (OGTT) at baseline and 4-years follow-up. Nine subjects developed either impaired glucose tolerance or type 2 diabetes at follow-up. At baseline, SELENOP concentrations correlated negatively with insulinogenic index, but not with homeostasis model assessment-estimated insulin resistance (HOMA-IR). Multivariate analysis showed that baseline SELENOP predicted fasting plasma glucose at follow-up independently of the other parameters. The receiver operating characteristic (ROC) curve analysis showed that baseline concentrations of serum SELENOP, but not of selenium, were a reliable test to predict future onset of glucose intolerance. In conclusion, elevation of circulating SELENOP, but not of circulating selenium, was positively and independently associated with future onset of glucose intolerance in a general Japanese population.

Background FOLFIRINOX (FFX) and gemcitabine (GEM) plus nab-paclitaxel (GnP) have recently been available for treating pancreatic ductal adenocarcinoma (PDAC). We investigated trends in characteristics, treatment and outcomes of unselected patients with unresectable PDAC in real-life practice in Japan. Methods We retrospectively reviewed the medical records of 1085 patients diagnosed as having unresectable or recurrent PDAC in multiple centers in the Hokuriku area between January 2009 and July 2015. Results The incidence of pathologically proven PDAC had increased from 18.7% in 2009 to 56.2% in 2015. Oncological therapy was administered to 779 patients (71.8%): chemotherapy (n = 675), chemo-radiotherapy (n = 92) or radiotherapy (n = 12); the remaining patients were treated with best supportive care. Of 100 patients diagnosed in 2009, 62.0% received GEM as first-line chemotherapy; whereas 30.7% of the 75 patients diagnosed in 2015 received FFX, 25.3% GnP, 22.7% GEM and 17.3% S-1. The objective response rates of patients treated with FFX, GnP and GEM were 14.9%, 35.0% and 5.5%, respectively and the OS 10.3, 9.9 and 7.5 months after FFX, GnP and GEM, respectively. Grade 3 or greater any hematological toxicity occurred in 70.2%, 70.0% and 18.8% of the patients treated with FFX, GnP and GEM, respectively. The reasons for treatment discontinuation were adverse events in 9.8%, 26.7% and 24.1% of the patients treated with FFX, GnP and GEM, respectively. Conclusion Chemotherapeutic protocols changed dramatically between 2009 and 2015. Continuous collection and analysis for our cohort with longer follow-up provides useful information about treatment selection and prediction of outcome.

The liver is a multifunctional organ with roles in metabolism, detoxification, and the immune response. Liver secretory selenoprotein P (SeP), a hepatokine, causes insulin resistance in the liver and peripheral muscle. We showed hepatitis C virus (HCV) infection increased serum SeP levels, which may explain the increased risk of type 2 diabetes in patients with HCV infection. Increased SeP mRNA (SEPP1 mRNA) in hepatocytes inhibited type 1 interferon response by means of undefined unique mechanisms. We revealed SEPP1 mRNA directly bound to retinoic acidinducible gene I (RIG-I), a virus RNA sensor, and inhibited RIG-I activity. The robust induction of interferon-stimulated genes (>1000-fold) and repression of HCV replication (>10-fold) were observed in hepatocytes in which SEPP1 mRNA was knocked down. Clinically, high SeP serum levels were significantly associated with treatment failure of direct actingantivirals for HCV. Thus, SeP regulates insulin resistance and innate immunity, possibly inducing immune tolerance in the liver.

Background and aim Relapse and diabetes mellitus (DM) are major problems for the prognosis of autoimmune pancreatitis (AIP). We examined the prognosis of type 1 AIP after corticosteroid therapy (CST)-induced remission in terms of relapse and DM. Methods The study enrolled 82 patients diagnosed with type 1 AIP who achieved remission with CST. We retrospectively evaluated the relapse rate in terms of the administration period of CST, clinical factors associated with relapse, and the temporal change in glucose tolerance. Results During follow-up, 32 patients (39.0%) experienced relapse. There was no significant clinical factor that could predict relapse before beginning CST. AIP patients who ceased CST within 2 or 3 years experienced significantly earlier relapse than those who had the continuance of CST (p = 0.050 or p = 0.020). Of the 37 DM patients, 15 patients (40.5%) had pre-existing DM, 17 (45.9%) showed new-onset DM, and 5 (13.5%) developed CST-induced DM. Patients with new-onset DM were significantly more likely to show improvement (p = 0.008) than those with pre-existing DM. Conclusions It was difficult to predict relapse of AIP based on clinical parameters before beginning CST. Relapse was likely to occur within 3 years after the beginning of CST and maintenance of CST for at least 3 years reduced the risk of relapse. The early initiation of CST for AIP with impaired glucose tolerance is desirable because pre-existing DM is refractory to CST.

Background Selenoprotein P (SeP), a selenium-rich extracellular glycoprotein, is the primary selenoprotein in the plasma. SeP plays an important role in the maintenance of selenium levels in the peripheral tissues. We developed a new sol particle homogeneous immunoassay (SPIA) for measuring full-length SeP (FL-SeP) levels in the human serum. Methods We used colloidal gold particles coated with two types of anti-SeP monoclonal antibodies, one recognizing the N-terminal side domain of SeP and the other recognizing the C-terminal side domain. Results The assay range was 0.2–9 mg/l, and the linearity was excellent. The within-day and between-day coefficients of variation ranged from 0.73% to 2.24% and 0.45% to 1.11%, respectively. Serum samples (n = 200) were examined using the newly developed assay system (employing a Model 7070 Hitachi automatic clinical analyzer) and the conventional enzyme-linked immunosorbent assay. These two methods were compared using the Passing–Bablok regression analysis; the resulting regression equation and correlation coefficient were y = 0.940x + 0.165 and r = 0.954, respectively. Conclusions Our new SPIA assay is a fully automated homogeneous immunoassay that can be used in conjunction with various commercial analyzers. The assay was sensitive, precise, and suitable for clinical measurement of the FL-SeP in the human serum.

Patients infected with hepatitis C virus (HCV) have an increased risk of developing type 2 diabetes. HCV infection is linked to various liver abnormalities, potentially contributing to this association. We show that HCV infection increases the levels of hepatic selenoprotein P (SeP) mRNA (SEPP1 mRNA) and serum SeP, a hepatokine linked to insulin resistance. SEPP1 mRNA inhibits type I interferon responses by limiting the function of retinoic-acid-inducible gene I (RIG-I), a sensor of viral RNA. SEPP1 mRNA binds directly to RIG-I and inhibits its activity. SEPP1 mRNA knockdown in hepatocytes causes a robust induction of interferon-stimulated genes and decreases HCV replication. Clinically, high SeP serum levels are significantly associated with treatment failure of direct-acting antivirals in HCV-infected patients. Thus, SeP regulates insulin resistance and innate immunity, possibly inducing immune tolerance in the liver, and its upregulation may explain the increased risk of type 2 diabetes in HCV-infected patients.

金沢大学医薬保健研究域医学系, We report the case of an 80-year-old female suffering from pancreatic cancer who developed severe non-alcoholic steatohepatitis (NASH) resulting in fatal hepatic failure after anti-cancer chemotherapy with gemcitabine. Hepatic encephalopathy appeared 1 year after the chemotherapy, and the patient developed progressive liver failure and eventually died. Radiological examination showed severe fatty liver. Histopathological examination of a liver needle necropsy showed almost panlobular macrovesicular fatty change. Ballooning degeneration and necrosis of hepatocytes accompanying neutrophil infiltration, Mallory bodies, and a few bile plugs were found in zone 3. Marked perivenular and pericellular/perisinusoidal fibrosis and extensive bridging fibrosis were also found. Together, these findings indicated steatohepatitis at a precirrhotic stage. Because the patient had no history of drinking in excess, we made a diagnosis of NASH, in particular, chemotherapy-associated steatohepatitis (CASH). Gemcitabine is a pyrimidine nucleoside antimetabolite with anti-cancer activity. A few reports have mentioned fatal hepatotoxicity caused by gemcitabine, but, to our knowledge, this is the first report of steatohepatitis, possibly associated with gemcitabine. Physicians treating patients with this drug should be aware of the possibility of steatohepatitis. © Springer 2010.

CAP, a multiple-drug combination therapy using cyclophosphamide (750 mg/m2), adriamycin (20-30 mg/m2) and cisplatin (50-75 mg/m2), was applied to 69 cases of epithelial ovarian cancer. The results of this therapy were compared with those of FAM (involving 5-fluorouracil, cyclophosphamide and mitomycin C) in 47 cases of the same cancer, retrospectively. The 5-year survival rate was 61.6% for cases treated with CAP and 56.3% for cases treated with FAM. All 9 patients at stage Ia treated with CAP are free of disease, however, 3 patients out of 13 at stage Ia treated with FAM experienced a recurrence of the disease and died. In stage III and IV cases with detectable lesions, a response was observed in 61.3% (19/31) treated with CAP and in 10.5% (2/19) treated with FAM.

A 29-year-old man with ulcerative colitis presented to the hospital complaining of persistent back pain. Pancreatic enzymes and tumor markers were elevated; imaging showed diffuse narrowing of the main pancreatic duct associated with diffuse pancreatic enlargement. We therefore performed an endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) biopsy of the pancreas using a 19-gauge needle. Histopathology revealed interlobular fibrosis, neutrophil infiltration in the intralobular ducts and acini, and very few immunoglobulin G4-positive cells. The patient was diagnosed with type 2 autoimmune pancreatitis and started on oral steroids; subsequently, we observed an improvement in the pancreatic enlargement and duct narrowing. Histologically proven type 2 autoimmune pancreatitis is rare in Japan.

Aim: To describe the extremely rare case of an adenomyoma of the papilla of Vater. Case Report: A 42-year-old woman was hospitalized for epigastralgia and high fever. The clinical presentation and endoscopic, biochemical, and radiologic findings led to the diagnostic impression of a dysfunction of the papilla of Vater. The patient was treated successfully by laparotomy and duodenotomy, incorporating cholangiomanometry and cholangiography. Intraoperative frozen-section examination of a transduodenal papillectomy specimen led to the diagnosis of adenomyomatosis of the papilla. The patient is doing well 38 months postoperatively. Conclusion: Such a combined approach to intraoperative diagnosis was important to avoid excessive surgery for a benign periampullary disease.

We investigated the expression of the drug resistance-related genes, multidrug resistance gene 1 (MDR1), multidrug resistance associated protein gene (MRP), and the DNA topoisomerase IIalpha, DNA topoisomerase IIbeta, and glutathione-S-transferase pi gene (GST-pi) in three human hepatoma cell lines (HepG 2, HuH 7, SK-Hep-1) with or without drug treatment with interferon-alpha (IFN-alpha) and cisplatin (CDDP), by a reverse transcription-polymerase chain reaction (RT-PCR) method and a competitive PCR method. The signals of the MDR1, MRP, topoisomerase IIalpha, and topoisomerase IIbeta genes in HepG2 were weakened when IFN-alpha was added to CDDP. In SK-Hep-1, the administration of CDDP alone increased the signals of MDR1 while the addition of IFN-alpha decreased the signals, and the signals of GST-pi were decreased by IFN-alpha plus CDDP. In summary, our results concerning the expression of drug resistance-related genes in three human hepatoma cell lines demonstrate that IFN-alpha may modulate the mechanism of resistance to CDDP in liver cancer.

A 73-year-old man with general malaise and nausea following a common cold diagnosed by a local physician was found to have multiple hepatocellular carcinomas with enlarged bilateral adrenal glands, combined with adrenal insufficiency. Hydrocortisone replacement improved the symptoms and laboratory findings. Autopsy findings revealed that each adrenal gland was completely replaced by the tumor measuring 11 cm in diameter, and no adrenal tissue was recognized. Histologically, the adrenal tumors, as well as the liver tumors, were moderately differentiated Edmondson type II hepatocellular carcinomas. This is a second report of adrenal insufficiency due to hepatocellular carcinoma as a primary site of metastatic adrenal tumor.

A 22-year-old woman developed sudden hepatic encephalopathy and severe intestinal bleeding. She was diagnosed with acute fatty liver and hypersensitivity vasculitis and was successfully treated with whole plasma exchange, methylprednisolone pulse therapy, and transcatheter arterial embolization. Twenty-seven months later, she began complaining of lower abdominal fullness, tenderness, and nausea and vomiting. Histologic examination showed that she had developed gastrointestinal and renal amyloidosis with intestinal pseudoobstruction and proteinuria. The immunohistochemical study of the stomach, rectum, and kidney with anti-amyloid A fluorescent antibody showed that the systemic amyloid deposit was secondary to her underlying disease. This is the first report of amyloidosis occurring secondary to hypersensitivity vasculitis.

We report a cirrhotic patient with complete occlusion of the portal vein with marked cavernous transformation due to chronic thrombosis in whom a transjugular intrahepatic portosystemic shunt (TIPS) was successfully created after direct minilaparotomy mesenteric vein catheterization, lysis and aspiration of the thrombus, and stenting in the portal vein. The methods used, we believe, provide a new technique for performing TIPS in chronically thrombosed portal veins in which previously no effective surgical therapeutic options were available.

症例は35歳男性.1965年より露光部に紅斑・浮腫が出現し,1987年,赤血球中プロトポルフィジン(PP)の高値より造血性プロトポルフィリン症(EPP)と診断された.1994年,肝障害にて当科入院.入院時の血液生化学検査で,AST 63IU/l, ALT 92IU/l, γGTP 303IU/lの肝障害と赤血球中PP値の増加(7,606μg/l)を認めた.肝組織像では小葉構造は乱れ,一部に再生結節が認められた.偏光顕微鏡で重屈折性を示す,褐色色業沈着を肝細胞,Kupffer細胞に認め,以上よりEPPによる早期肝硬変と診断した.ケノデオキシコール酸900mg/日の投与により,ALTは30IU/lと正常化し,γGTP 63IU/l,赤血球中PP5, 748μg/lと低下した.EPPにおいては時に肝不全を呈することがあり,早期診断と肝機能の厳重な経過観察が必要である.本例ではケノデオキシコール酸療法が赤血球中PPの低下と肝機能の改善に有効であったと考えられた.

Non-radioisotopic reverse transcriptase assay (Non-RTA) was successfully applied for detection and identification of the retroviruses isolated from peripheral mononuclear cells from eight HIV-1-seropositive hemophiliac patients. Of 40 samples, 36 (90%) were consistent in detection between Non-RI and RI RTA. Four samples which showed RT activities slightly above the cutoff level of RI RTA were not detected by Non-RI RTA. Non-specific RT-inhibitors in the culture supernatant decreased the sensitivity of Non-RI RTA more significantly than that of RI RTA. It was demonstrated that higher concentrations (> 20%) of fetal calf serum in RPMI-1640 culture medium inhibited the hybridization of poly rA template with immobilized primer, resulting in reducing the sensitivity of Non-RI RTA. Then we identified the isolated retroviruses using specific RT-inhibiting (RTI) antibodies against HIV-1 and HIV-2. HIV-1 RTI antibody specifically inhibited RTs of isolated retroviruses and HIV-1 strain, LAV-1, but not HIV-2 and Rous-associated virus 2 (RVA-2) RT. Conversely, HIV-2 RTI antibody specifically inhibited HIV-2 RT, but not HIV-1 and RAV-2 RT. These findings agreed with previously reported results showing the type-specificity of HIV-1 and -2 RTI antibodies, and suggest the possibility that isolated retroviruses could be identified by these antibodies.

It is important to prevent unexpected laboratory infections in a biosafety area. It is recommended that extreme caution should be used when handling needles and syringes to avoid autoinoculation, and that needles and syringes should be used only when there is no alternative. To remove cells and cell debris, a disk-type microfilter unit, which is recommended using a needle, has been used for filtrating supernatant from HIV-1-infected cell cultures. We compared a stick-type microfilter unit, which can be used without a needle, with a disk-type one for their safety and recovery of human immunodeficiency virus particle after filtration. To confirm the right of our comparison, we observed the filter electron microscopically for the virus particles and virus suspensions were carried out and discussed. In conclusion, the stick-type filter should be improved, since the filter unit is inferior to the disk-type filter unit in purification of the virus, but for the safety is superior to the disk-type.

We developed a non-radioisotopic (non-RI) reverse transcriptase assay (RTA). The reverse transcriptase (RT) incorporates biotin-11-deoxyuridine-triphosphate (bio-dUTP) using a poly(rA) template hybridized with oligo(dT) primer that is immobilized on the surface of a 96-well microtiter plate. This assay is thus semi-automated by adapting it to an ELISA testing format. The incorporation of bio-dUTP was enhanced by adding cold dTTP to the reaction mixture, optimally in a molar ratio 4:1 (dTTP:bio-dUTP). This non-RI RTA is more sensitive than the conventional RI assay for the detection of purified Rous-associated virus 2 (RAV-2) and of human immunodeficiency virus type 1 (HIV-1) lysate. Because of its simple procedure, higher sensitivity and non-use of RI materials, the assay can be utilized not only for virological studies but also for routine safety screening of biological products for retroviral contamination.

患者は56歳男性.身体所見上,大腿から下腿にかけての浮腫,正中線上8横指にわたる肝腫大,腹壁静脈の怒張を認めた.検査成績では免疫グロブリンの著しい低下を認め,骨髄穿刺所見および血清,尿の免疫電気泳動結果より多発性骨髄腫と診断された.肝生検像では類洞内に肝細胞の萎縮を伴うアミロイドの著しい沈着を認め,多発性骨髄腫に伴うアミロイドーシスと診断した.本例での下大静脈造影では肝により広範囲に肝部下大静脈の圧排狭窄が認められた.下肢の浮腫の原因として腫大した肝による肝部下大静脈圧排に基づく還流障害が考えられた.また本例での肝静脈楔入圧は21mmHgと上昇しており,門脈圧亢進の機序として,アミロイドの類洞内沈着による門脈血流の障害に加え,腫大した肝による肝静脈流出路圧排に基づく血流障害,すなわちBudd-Chiari syndromeの可能性も考えられた

The whole-cell voltage-clamp method was applied to single smooth muscle cells prepared from the longitudinal layer of the pregnant rat myometrium (17-20 days of gestation). It was found that the transient inward current mainly consists of Ca2+ current, because the removal of Ca2+ ions from the external medium and 10 microM nifedipine eliminated this inward current. Its steady-state inactivation curve was obtained by the standard method, in which the membrane potential of half inactivation and the slope factor were estimated to be -58.0 +/- 4.9 mV (n = 11) and 8.9 +/- 1.4 mV (n = 11), respectively. In a small number of preparations (in 2 out of 30 preparations), there remained a very fast inward current in Ca(2+)-free medium containing Mg2+. Tetrodotoxin (TTX, 10 microM) can can abolish this current, suggesting that the channel for this current is equivalent to the Na+ channel in nerve cells. Two major phases of outward currents were identified by voltage jumps from negative holding levels to more positive levels. The first phase was a fast transient outward current. This current remained intact after external tetraethylammonium (TEA, 20 mM) was added. Following the transient current, a large delayed rectified outward current reached its peak over a period of 50 ms and then decayed. The reversal potential for this outward current was determined by observing the change of polarity of the tail currents with the change in extracellular K+ concentration [( K+]o). The slope for the change of reversal potential per ten-fold change in [K+]o is 57.7 mV at more than 23.2 mM [K+]o, indicating that this current is mostly carried by K+ ions. Voltage-dependent inactivation of the delayed rectified outward current was determined by the standard method. The membrane potential for half inactivation and the slope factor were estimated to be -42.8 +/- 3.9 mV (n = 3) and 10.1 +/- 1.5 mV (n = 3), respectively. External TEA (20 mM) effectively eliminated the delayed rectified outward currents. Nifedipine (10 microM) suppressed not only Ca2+ current but also outward K+ currents.

インターフェロン(IFN)療法を施行した非A非B型肝炎25例を対象に,IFN投与開始後1カ月以内に血清GPTが正常化した群と改善の認められなかった非正常化群の判別を試みるため各種背景因子の多変量解析を行なった.15項目の単変量解析(t-test, chi-square test)の結果,正常化群は非正常化群に比べ,より若年で,治療前2-5AS活性値と2-5AS活性最高値は低値であったが,IFN投与後の増加率は高く,その差は有意であった.また,治療前GPT値は正常化に低値の傾向が認められた.この5変量を用いた多変量解析(判別判定法)にて作成された線形判別式の的中率は19例中18例(94.7%)であり,各変量の判別に対する貢献度は年齢がもっとも高く,以下2-5AS増加率,最高値,治療前GPT値,治療前2-5AS活性値であった.以上の結果から,多変量解析により非A非B型肝炎でのIFN治療効果は判別可能と考えられ,また,個々の例では2-5AS増加率がより上昇するIFN投与量,投与方法が選択されるべきと考えられた.

輸血後C型肝炎の遷延化に対する長期インターフェロン(IFN)療法が関与したと思われる甲状腺機能亢進症を発症した1例を経験した.症例は49歳,男性.胃潰瘍からの大量出血に対して1,440mlの輸血を受け,輸血40日後に輸血後肝炎を発症.肝炎発症時,抗マイクロゾーム抗体は陽性であったが,甲状腺機能は正常状態であった.遷延化傾向を認めた肝炎に対し,組み換え型IFNα総計474×106単位を12ヵ月間,皮下投与した.IFN投与終了9ヵ月後より手指振戦が出現,2ヵ月間で10kgの体重減少を認め,また,血中甲状腺ホルモンの上昇を認め甲状腺機能亢進症と診断した.IFN治療開始後,甲状腺刺激抗体,TSH受容体抗体および抗核抗体は新たに陽性化,抗マイクロゾーム抗体に抗体価の上昇を認めた.長期IFN療法に関連し,自己抗体が陽性化し自己免疫疾患としてのGraves病を発症した1例と考えられ,今後IFN療法に際して留意すべき問題点と考え報告した.

Esophago-gastric varices of 22 patients were studied using a newly developed method of endoscopic ultrasonography (EUS). During the observation, the esophagus was filled with de-aerated water, and reflux of the water was prevented using a balloon placed 7 cm proximal to the tip of the endoscope. Thirteen of 22 patients received endoscopic sclerotherapy (EIS) for their esophago-gastric varices, and sequential changes of the varices were observed mith EUS. The EUS method demonstrated esophago-gastric varices as singular, or a bundle of low-echoic luminal structures, and extramural collateral vessels were also observed. Therefore, it was possible to evaluate the residual blood flow after EIS by the EUS findings. Sequential changes of the treated varices were observed as follows: (1) formation of a thrombus in the varices, (2) thickening of variceal wall, and (3) disappearance of luminal structures. Small luminal structures in the extramural space of the lower esophagus, dilated paraesophageal veins, were detected in 6 of 13 patients with EIS. The recurrence rate was smaller and the remission period was longer in these 6 patients than those in patients without these luminal structures. Our new EUS method has been shown to be useful not only for the morphological evaluation of varices, but also for the assessment of the effect of EIS.

無症候性原発性胆汁性肝硬変(a-PBC) 31例を対象として,その自然経過とursodeoxy-cholic acid (UDCA)投与後の経過について,項目別にスコア化した組織変化を含め臨床病理学的に検討した.3～94ヵ月(平均32ヵ月)の自然経過では血液生化学的に有意な変動はみられず,症候性への移行を31例中4例(12.9%)に認め,うち1例では診断後94ヵ月後に肝不全にて死亡した.一方,UDCA (600mg/日)を投与した16例では,3ヵ月後よう肝胆道系酵素,IgM値の有意な減少が認められた.組織所見については,UDCA非投与期では胆管炎のスコアのみが低下したが,UDCA投与期では胆汁うっ滞,胆管炎,線維化,グ鞘炎の各スコアにいずれも有意の改善が認められた.以上より,一部のa-PBCは緩徐ながら進行性で,s-PBCへの移行が認められた.一方,UDCA療法は血液生化学的,組織学的に有意の改善をもたらしたことから,a-PBCに対する有効な治療法である可能性が示唆された.

We have reported a rare case of multiple intrahepatic portal-hepatic venous shunts, who developed hepatic coma as the first clinical manifestation.A 60-year-old female was entered to our hospital because of recurrent coma attacks accompanied with hyperammonemia and triphasic wave on EEG. Laboratory data were almost normal except for hyperammonemia and retardation of ICG, and marked increase of heart/liver ratio was found on 201Tl perrectal scintigraphy. Imaging studies using ultrasonography, CT during arterial portography (CT-AP) and MRI suggested multiple intrahepatic portal-hepatic venous shunts, and hepatic venography demonstrated a total of eight macroscopic shunts retrogradely. There was no finding of chronic liver disease on peritoneoscopy or histopathological study of liver specimen. Administration of lactulose and branched chain amino acids has improved serum ammonium level, and she has been completely free of hepatic encephalopathy after medication.

We reviewed the clinical features and clinical course of patients with duct-narrowing chronic pancreatitis who were negative for immunoserologic test results (n = 16) in comparison with the findings for serological test-positive patients (n = 20) in order to determine an adequate treatment for those who had typical morphology of autoimmune pancreatitis in the absence of immunoserologic abnormality. No significant differences were found between the two groups of patients in clinical profiles including associated autoimmune-related diseases, pancreatic histology, and response to steroid therapy. Of the seronegative patients, eight who showed an improvement in narrowing of the main pancreatic duct with steroid therapy and three who did no show an improvement or who relapsed after surgical resection without this therapy had stenosis of the common bile duct with increased levels of serum hepatobiliary enzymes, except for two patients with affected sites limited to the body or tail of the gland. For the remaining five patients, who showed an improvement in pancreatic duct changes or long-term remission after surgery without steroid administration, normal biochemistry test results for liver functions were obtained, with no abnormal cholangiographic findings in the three patients examined. Duct-narrowing chronic pancreatitis without immunoserologic abnormality overlaps in clinical features with that fulfilling the immunoserologic criteria for a diagnosis of autoimmune pancreatitis. In particular, the disease with bile duct involvement should be treated clinically as autoimmune pancreatitis, for which steroid therapy is recommended, even if an autoimmune mechanism is not demonstrated serologically.

It is well known that neuropathy, myelopathy, and arthropathy are specific adverse effects induced by paclitaxel administration. Parkinson's disease is neural degenerative disease, and the influence of paclitaxel administration on patients with Parkinson's disease is unknown. We have successfully treated an ovarian cancer patient with Parkinson's disease by paclitaxel/CBDCA combined chemotherapy after surgery. The patient was a 57-year-old woman with solid and cystic ovarian tumor. Among the tumor markers CA125, CA19-9, and SLX, only SLX was elevated. We operated and made a pathological diagnosis of the ovarian tumor as clear cell adenocarcinoma (FIGO stage Ic). After surgery, the patient was treated with paclitaxel (260 mg [175 mg/m2]) and CBDCA (600 mg [AUC = 5]) combined chemotherapy for 5 courses. Her status is complete remission. During chemotherapy, she had felt the decreased efficacy of her Parkinson's disease medication. We could continue chemotherapy by increasing the dose of the Parkinson's drug. There is only one case report on the influence of paclitaxel on Parkinson's disease, in which the course was similar to the present case.

Patients with advanced hepatocellular carcinoma (HCC) have a poor prognosis, and the development of new therapeutic strategies is necessary. Here we report the efficacy of combination chemotherapy in our biochemical modulation. Synergistic effects of interferon-alpha-2b on 5-fluorouracil or cisplatin were demonstrated in Huh7 cells. The efficacy of methotrexate-5-fluorouracil, cisplatin, and interferon-alpha-2b combination therapy was demonstrated in 34 patients with HCC complicated by major portal vein thrombosis. Among the 29 patients eligible for the study, there were 3 complete responders and 10 partial responders with an overall response rate of 45%. The 2-year survival of the 34 patients was 15%, and the median survival of complete and partial responders was 11 months. There was severe transient hematological toxicity. Eight patients suffered from renal insufficiency, and 4 of them underwent hemodialysis. Although a control study is clearly necessary, our combination therapy induced a good response in the patients with advanced HCC. On the basis of our results, intensive chemotherapy should be attempted in advanced HCC complicated by major portal vein invasion.

Equilibrium measurements were performed to obtain the N 2 pressure-composition isotherms at 400, 600 and 800 °C for a single-phase α-U 2 N 3+ x (0 ≦ x ≦ 1) region, using N-rich α-U 2 N 3+ x (atomic ratio N/U > 1.80) as the starting material. The equilibrium compositions of α-U 2 N 3+ x at 800 °C were also determined by equilibrating U metal with N 2 gas.

Recent advances in the treatment of hepatocellular carcinoma (HCC) have changed the importance of bone metastasis during the follow up of such patients. In the present study, we investigated risk factors for bone metastasis after treatment for HCC.Two hundred and two patients with HCC were diagnosed as free of bone metastasis by technecium 99m-methylene diphosphonate bone scintigraphy and were followed prospectively after treatment of the primary lesions (follow-up period 2-146 months; median 20 months). We statistically analyzed the risk factors for bone metastasis using the clinical characteristics at the time of first treatment.Multiple tumors (P0.005), main tumor size5 cm in diameter (P0.005), the presence of distant metastasis (P0.005), elevation of serum alpha-fetoprotein (100 ng/mL; P0.05), chemotherapy (P0.05) and insufficient therapeutic response (P0.0005) were identified as risk factors for bone metastasis by univariate analyses. Insufficient therapeutic response and main tumor size5 cm in diameter (both P0.05) were identified as independent predisposing factors for bone metastasis.Complete necrosis of primary HCC during the first treatment is important to prevent subsequent bone metastasis.

Forty-three patients with hepatocellular carcinomas (HCCs) who had undergone subsegmental transcatheter arterial embolization (sTAE) as initial treatment were studied retrospectively to evaluate the prognosis, recurrence, and effect of sTAE on liver function. Frequent recurrences were observed (disease-free survival rates were 51.2% at 1 year and 7.7% at 3 years), and in the recurrent nodules, 66.4% were distant recurrences. No significant difference was observed in the periods of distant recurrence compared with local recurrence, and also in the periods of distant recurrence with and without local recurrence, implying that strict control of the primary lesion did not prevent distant recurrence. Concerning the effect of sTAE on liver function, ALT and LDH were significantly elevated and albumin was significantly reduced after sTAE (p = 0.002, > 0.0001, and = 0.0009, respectively). But 4 weeks after sTAE, all these levels recovered to their previous values. Moreover transient hepatic reserve reduction after sTAE did not affect the prognosis. In conclusion, for HCCs with such levels of recurrence, strict follow-up and repeat treatments with minimum damage to the hepatic reserve are essential. sTAE is an appropriate and reasonable treatment for such HCCs because of low levels of damage to the hepatic reserve and the possibility of repeat operations. Using sTAE as the main treatment against HCC, survival rates of more than 70% at 3 years were achieved.

We tested whether human immunodeficiency virus type 1 (HIV-1) could be differentiated from HIV-2 by a reverse transcriptase (RT)-typing assay that measured the reduction of enzyme activity owing to specific antibody. RT-inhibiting antibody was examined for HIV type specificity by a new nonradioisotopic RT assay. Antibodies from four rabbits immunized with recombinant HIV-1 RT and from 23 HIV-1-seropositive individuals all specifically inhibited the enzyme activities of two HIV-1 strains (LAV-1 and GH-3), three zidovudine-resistant HIV-1 mutants, and a recombinant HIV-1 RT. However, none of these antisera affected the activities of six HIV-2 strains (GH-1, GH-2, GH-4, GH-5, GH-6, LAV-2ROD), Rous-associated virus type 2, and DNA polymerase I from Escherichia coli. In contrast, HIV-2 antibody from a rabbit immunized with disrupted GH-1 virions blocked the enzyme activities of the six HIV-2 strains but not those of the three HIV-1 strains, Rous-associated virus type 2, or DNA polymerase I. These results indicate that the antigenic domains of HIV-1 and HIV-2 RTs recognized by their inhibiting antibodies are distinct from each other and are highly conserved. Clinical HIV isolates from 18 HIV-1-seropositive individuals and 3 HIV-2-seropositive Ghanaian individuals were identified as HIV-1 and HIV-2, respectively, by the nonradioisotopic RT-typing assay.

Clinical and pathological details of 10 patients with stage I low malignant potential tumors of the ovary, between September, 1969, and February, 1988, have been reviewed. The mean age of the patients was 46.6 years. Six patients had serous and four had mucinous tumors. Of the 10 patients, five had a unilateral salpingo-oophorectomy, one had a bilateral salpingo-oophorectomy and four a total abdominal hysterectomy and bilateral salpingo-oophorectomy. The mean duration of follow-up was 12.8 years. All patients have remained alive and disease-free. A recurrence occurred in one patient who has been managed well by additional surgery. Stage I ovarian tumor of low malignant potential appears to carry a favorable prognosis.

A case of ovarian cystadenocarcinoma associated with pregnancy is reported. The semicystic left ovarian tumor was found in a 28-year-old woman, gravida 2, para 1 at 33 weeks' gestation. A primary Cesarean section, total abdominal hysterectomy and bilateral salpingo-oophorectomy followed by chemotherapy were performed. The histological examination revealed the tumor to be a serous cystadenocarcinoma. The patient and infant have both remained well and free of disease for the eight years which have elapsed since the therapy started.

Alagille症候群の1成人例を報告した.症例は20歳,女性,家族歴にて母に肝障害および高脂血症を認めた.生下時より心雑音,黄疸を指摘され,黄疸は軽快したが10歳頃まで皮膚掻痒感を認めた.10歳時,肝障害を指摘され当科第1回入院し,慢性非活動性肝炎と診断され,同時に高脂血症,肺動脈弁狭窄症疑い,脊椎骨の変形を指摘されたが以後放置していた.昭和61年再び肝障害,高脂血症を指摘され精査のため第2回入院となった.特徴的顔貌,末梢性肺動脈狭窄症,蝶型椎,肝内,肝外胆管の狭小化,角膜周辺の胎生環などの所見が認められ.Alagille症候群と診断した.肝生検では門脈域の胆管系が全く欠如しており,腎生検では尿細管上皮細胞の変性が認められた.また腹部画像診断では,肝左葉内側区域の腫大が認められた.本症候群はこれまで主に小児科より報告されているが,予後良好で無症状で経過する例もあり,内科領域でも注目する必要があると考えられた.

A homologous blood transfusion is often required to replace intraoperative blood loss in a radical hysterectomy. Recently, we have tried the simultaneous use of autotransfusion (predonation and transfusion of autologous blood) and hypotensive anesthesia to eliminate the homologous blood transfusion. Radical hysterectomy was done in 27 cases with uterine cancer from June 1986 to March 1987 at the Kure National Hospital. A homologous blood transfusion was required in 1 of 5 cases with only autotransfusion, none of 5 cases with a simultaneous use of autotransfusion and hypotensive anesthesia, and 6 of 17 cases with neither autotransfusion nor hypotensive anesthesia. The simultaneous use of autotransfusion and hypotensive anesthesia seemed to be effective in reducing the need for homologous blood transfusions.

The uptake of cephalosporin antibiotics, cephalexin, was studied with brush-border microvillous plasma membrane vesicles prepared and purified from human full-term placental syncytiotrophoblasts. The uptake of cephalexin by the membrane vesicles was not stimulated in the presence of an Na+ gradient from the outside to the inside of the vesicles, whereas alpha-(methylamino)isobutyrate uptake into the vesicles of the same preparation was stimulated by an Na+ gradient. The equilibrium level of cephalexin uptake decreased with increasing osmolarity of the medium, which indicates that cephalexin is transported into the membrane vesicles. When cephalexin concentrations were varied, the initial rate of uptake obeyed Michaelis-Menten kinetics with Km and Vmax values of 2.29 mM and 2.98 nmol/mg of protein per 60 s, respectively. The uptake of cephalexin was inhibited by structural analogues and sulfhydryl modifying reagents. These results indicate the existence of a carrier-mediated transport system for cephalexin in the human placental brush-border membranes.