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Background: Careful nutritional support is required in patients with liver cirrhosis due to their glucose intolerance. To elucidate the mechanism of glucose intolerance in cirrhotics, we measured insulin secretion, whole body insulin sensitivity (SI), and glucose sensitivity (SG) in non-diabetic cirrhotics.Methods: Eight patients with compensated cirrhosis who showed normal fasting blood glucose levels and non-diabetic curves on a 75 g oral glucose tolerance test participated in this study. Four normal volunteers were selected as controls. After an overnight fast, glucose was injected intravenously at 300 mg kg(-1) in 2 min followed 20 min later by intravenous insulin at 0.02 U kg(-1) in 5 min. Sequential blood samples were drawn from 20 min before the glucose injection to 3 h post-injection, and plasma glucose and insulin levels were determined. Plasma glucose and insulin disappearance curves were analyzed using the minimal compartment model, and kinetic parameters, including glucose clearance (KG), insulin secretion, SI and SG, were estimated.Results: KG was slower in cirrhosis than in controls, although not significant (P=0.051). Insulin secretion was not different between the two groups. However, SI was significantly lower in cirrhotics (0.814x10(-4) min(-1) pM(-1); 0.572-1.403x10(-4) min(-1) pM(-1)) as compared to controls (1.643x10(-4) min(-1) pM(-1); 0.678-2.085x10(-4) min(-1) pM(-1)) (P=0.029). SG was also lower in the cirrhosis (0.0154 min(-1); 0.0071-0.0208 min(-1)) than in the control group (0.0211 min(-1); 0.0184-0.0260 min(-1)) (P=0.026).Conclusion: Both SI and SG are already impaired in non-diabetic cirrhotic patients even when KG is minimally delayed and insulin secretion has not yet been affected.

Inflammatory pseudotumor (IPT) of the liver is a rare benign variant of hepatic masses, and its exact etiology has not been elucidated. We report a case of IPT associated with primary sclerosing cholangitis (PSC). The patient was a 50-year-old man admitted to our hospital because of jaundice. Abdominal ultrasonography (US) and computed tomography showed multiple dilations of the intrahepatic bile ducts and multiple masses in the liver. On magnetic resonance imaging, the masses were slightly hypointense on T1-weighted images and slightly hyperintense on T2-weighted images. On T1-weighted images after the bolus infusion of Gd chelate, the masses had no contrast enhancement, and they were hypointense in the arterial phase and portal venous phase. However, they were slightly enhanced and became almost isointense relative to the surrounding normal liver parenchyma in the delayed phase. Endoscopic retrograde cholangiography demonstrated multiple irregular strictures and dilations of the intrahepatic bile ducts. Angiography demonstrated no abnormal findings, but, interestingly, subsequent dynamic CO2-enhanced US showed a strongly hyperechoic string, indicating that an artery had penetrated through the hypoechoic mass. A US-guided percutaneous needle biopsy revealed that the lesions were morphologically comparable to IPT. After cholangiography and microscopic analysis of the tumor, the final diagnosis was determined to be IPT of the liver with PSC. A number of previous reports have suggested a possible relationship between IPT and PSC, based on pathological findings. This report confirmed, based on clinical findings, that PSC is one of the causes of hepatic IPT.

Background/Aims: Fulminant hepatitis usually takes a rapidly progressive course, terminating in death within a short period. Experimental studies have demonstrated that immunological mechanisms play an important role, especially those involving virus-specific CD8 + cytotoxic T lymphocytes and their production of interferon-gamma (IFN-γ). However, there are no immunological markers for prediction of the development of fulminant hepatitis in man. Methods: Peripheral blood lymphocytes from four patients with fulminant hepatitis, six with acute hepatitis and 11 healthy volunteers as normal controls were analyzed. Intracellular IFN-γ production in both CD8 positive and negative T lymphocytes was assessed by flow cytometry. Results: Populations of CD8 + IFN-γ + T lymphocytes were significantly increased in patients with fulminant hepatitis, as compared with those with acute hepatitis and normal controls. Production of IFN-γ in CD8 + T lymphocytes of patients with fulminant hepatitis was also elevated, furthermore significantly correlating with the prothrombin time ( r =−0.64, p Conclusions: The capacity for IFN-γ production by CD8 + lymphocytes is up-regulated in fulminant hepatitis, and this may be important for the development of fulminant hepatitis.

Background Endoscopic papillary balloon dilatation (EPBD) is generally considered a safe and effective technique for removal of common bile duct (CBD) stones. However, some reports have prompted concern about the risk of pancreatitis following the procedure, and it seems to be more difficult and to require adjunctive procedures more frequently in patients with large stones. Aims To analyse the factors influencing pancreatitis after the procedure, and to examine which is the more suitable adjunct for treating large stones, mechanical lithotripsy (ML) or extracorporeal shockwave lithotripsy (ESWL). Patients and methods EPBD was performed in 92 patients, including 40 with large stones (≥ 12 mm). These 40 patients were randomly assigned to two groups receiving ML or ESWL to fragment stones (20 patients each). Results Complete ductal clearance was obtained in all 92 patients. Significant elevation of the serum amylase level compared with the prior value (> 300 IU/I) was observed in 26 (28%), and eight (8.7%) developed clinical pancreatitis. To assess the influence of various factors on the amylase level, multivariate analysis was used. The number of stones and the time required for treatment had a significant influence on the incidence of increased amylase level (P < 0.05), and ML also significantly increased it (P < 0.05). On the other hand, the amylase level remained low in the ESWL group. ML caused elevation of amylase level in 11 patients (55%), while three (15%) had elevation after ESWL. Conclusions In patients with multiple stones, elevation of the amylase level is more frequent. This seems to be because repeated cannulation and much time is required for treatment. In patients with large stones, the rate was also high if ML was used, but was low when ESWL was used. ESWL may reduce the incidence of pancreatitis.

A 17-year-old woman was admitted because of a liver tumor found incidentally by ultrasonography. Liver function was normal and there were no markers of hepatitis viruses or malignancy. Abdominal ultrasonography, computed tomography (CT), and magnetic resonance imaging revealed a mass (2 cm in diameter) in the lateral segment of the left lobe of the liver. The lesion was not detected by hepatic arteriography. However, dynamic CT with fast scanning and dynamic CO2-enhanced ultrasonography demonstrated initial central enhancement of the mass followed by centrifugal spread of enhancement to the periphery. Color Doppler flow imaging detected a central color spot, shown to be an artery by a pulsed Doppler spectrum analysis. Fine-needle biopsy confirmed a diagnosis of focal nodular hyperplasia. Dynamic CT with fast scanning, dynamic CO2-enhanced ultrasonography, and color Doppler flow imaging were useful in detecting the vascular pattern specific to focal nodular hyperplasia. Investigation of further cases with these novel imaging modalities should help to establish a comprehensive diagnostic procedure and thus avoid unnecessary surgery for focal nodular hyperplasia, which is a completely benign lesion.

Epidemiologic data suggest that non-alcoholic fatty liver disease (NAFLD) have an increased tendency to occur in patients who are associated with metabolic conditions such as obesity, type 2 diabetes mellitus, and dyslipidemia. NAFLD represents a wide spectrum of conditions ranging from fatty liver, which in general follows a benign, no-progressive clinical course, to non-alcoholic steatohepatitis (NASH), a more serious form of NAFLD that may progress to cirrhosis and end stage liver disease. However, currently the diagnosis of NASH requires an invasive liver biopsy. The aim of this study is to evaluate whether Cytokeratin 18 (CK-18) has potential non-invasive diagnostic capability for the NASH. Serum levels of alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, adiponectin, leptin, and CK-18 were measured in 27 patients (8 patients with simple fatty liver, 6 fatty liver with fibrosis patients, 13 patients with NASH) and 23 healthy controls. Regarding gender difference in the control group, although both adiponectin and leptin significantly increased in the female compared with the male (p0.002 and p0.01, respectively), there were no significant gender differences in CK-18. For the conventional liver function tests, there were no significant differences in 4 groups. Serum levels of adiponectin was significantly lower in patients with NASH compared with the control group(p0.001), and both leptin and CK-18 were markedly higher in patients with NASH compared with control group (p0.001). These results suggested that measurement of serum CK-18 is useful for assessing the NASH.

Background In patients with hepatocellular carcinoma (hepatoma), the rate of recurrent and second primary hepatomas is high despite surgical resection and percutaneous ethanol-injection therapy. We developed an acyclic retinoid, polyprenoic acid, that inhibits hepatocarcinogenesis in the laboratory and induces differentiation and apoptosis in cell lines derived from human hepatoma. In a randomized, controlled study, we tested whether the compound reduced the incidence of recurrent and second primary hepatomas after curative treatment. Methods We prospectively studied 89 patients who were free of disease after surgical resection of a primary hepatoma or the percutaneous injection of ethanol. We randomly assigned the patients to receive either polyprenoic acid (600 mg daily) or placebo for 12 months. We studied the remnant liver by ultrasonography every three months after randomization. The primary end point of the study was the appearance of a histologically confirmed recurrent or new hepatoma. Results Treatment with polyprenoic acid significantly reduced the incidence of recurrent or new hepatomas. After a median follow-up of 38 months, 12 patients in the polyprenoic acid group (27 percent) had recurrent or new hepatomas as compared with 22 patients in the placebo group (49 percent, P = 0.04). The most striking difference was in the groups that had second primary hepatomas--7 in the group receiving polyprenoic acid as compared with 20 in the placebo group (P = 0.04 by the log-rank test). Cox proportional-hazards analysis demonstrated that as an independent factor, polyprenoic acid reduced the occurrence of second primary hepatomas (adjusted relative risk, 0.31; 95 percent confidence interval, 0.12 to 0.78). Conclusions Oral polyprenoic acid prevents second primary hepatomas after surgical resection of the original tumor or the percutaneous injection of ethanol.

Oxidative stress plays an important role in liver carcinogenesis. To determine the impact of oxidative stress on the recurrence of stage I/II hepatocellular carcinoma (HCC) after curative treatment, we conducted a prospective case series analysis.This study included 45 consecutive patients with stage I/II HCC, who underwent curative treatment by surgical resection or radiofrequency ablation at Gifu Municipal Hospital from 2006 to 2007. In these 45 cases, recurrence-free survival was estimated using the Kaplan-Meier method. The factors contributing to HCC recurrence, including the serum levels of derivatives of reactive oxygen metabolites (d-ROM) as an index of oxidative stress, were subjected to univariate and multivariate analyses using the Cox proportional hazards model.The serum levels of d-ROM (P = 0.0231), α-fetoprotein (AFP, P = 0.0274), and fasting plasma glucose (P = 0.0400) were significantly associated with HCC recurrence in the univariate analysis. Multivariate analysis showed that the serum levels of d-ROM (hazard ratio [HR] 1.0038, 95 % confidence interval [CI] 1.0002-1.0071, P = 0.0392) and AFP (HR 1.0002, 95 % CI 1.0000-1.0003, P = 0.0316) were independent predictors of HCC recurrence. Kaplan-Meier analysis showed that recurrence-free survival was low in patients with high serum d-ROM (≥570 Carr U, P = 0.0036) and serum AFP (≥40 ng/dL, P = 0.0185) levels.The serum levels of d-ROM and AFP can be used for screening patients with a high risk for HCC recurrence. Patients who show increased levels of these factors require careful surveillance.

Endoscopic sphincterotomy (ES) is widely performed in patients with common bile duct stones (CBDS). However, the long-term outcomes of patients following ES have not been sufficiently elucidated. Impaired papillary function following ES may result in additional late complications. In contrast, endoscopic papillary balloon dilation (EPBD)—another option for treating CBDS—is expected to preserve papillary function. This study aimed to compare the long-term outcomes of patients with CBDS treated with ES to those treated with EPBD in a large cohort. In addition, a subgroup analysis was performed, according to gallbladder (GB) status. A cohort study was performed using propensity score matching to reduce treatment selection bias. This involved the analysis of follow-up data for 1086 patients who underwent EPBD or ES for CBDS. Propensity score matching extracted 246 pairs of patients. The median (interquartile range) follow-up period after EPBD or ES was 93.5 (46.8–129.2) months and 90 (42–139.3) months, respectively. The incidence of CBDS recurrence after EPBD and ES were 8.5 and 15.0 %, respectively. The hazard ratio (95 % CI) was 0.577 (0.338–0.986) (P = 0.044). Based on the status of the GB, the incidence of CBDS recurrence was significantly different between post-EPBD and post-ES in the group with cholecystectomy after EPBD/ES (P = 0.013). The incidence of biliary complications was significantly lower in patients after EPBD than in those after ES, and this outcome appeared most markedly in patients who also underwent cholecystectomy.

Currently, endoscopic intervention is widely attempted as the first-line treatment of benign biliary strictures because of its convenience and low morbidity. Plastic tube stents (PS) are usually used for such treatment; however, covered self-expandable metallic stents (C-SEMS) are becoming more commonly used at some institutions. The temporary placement of C-SEMS may lead to better outcomes because of their larger diameter and, therefore, better dilation of the stricture, especially in refractory cases. The aim of the present study was to evaluate the efficacy of the temporary placement of C-SEMS in the management of benign biliary strictures.We retrospectively reviewed our endoscopic retrograde cholangiopancreatography (ERCP) database (May 1996 to December 2010), and extracted the data of patients who underwent endoscopic treatment for benign biliary strictures. Then, the follow-up data from patient charts were reviewed to determine the long-term outcomes of those procedures.All patients (n = 56) initially had a PS placed, with or without balloon dilation. However, C-SEMS placement was later attempted in 12 patients because the stricture was refractory to placement of the PS. During their follow-up periods, two patients died of unrelated diseases after 15 and 17 months, and another two still had the C-SEMS in place after 9 and 50 months. In the remaining eight patients, the C-SEMS was removed after a median placement period of 6 months (range, 2-15). Seven patients in this group have not experienced a recurrence at a median follow-up time of 48 months. However, in one patient, stenosis did recur 8 months after the C-SEMS was removed.Temporary placement of C-SEMS can be a treatment option for benign biliary strictures, especially in refractory cases.

Endoscopic biliary stenting is a well-established palliative treatment for unresectable malignant biliary strictures, for which plastic tube stents (PSs) and self-expandable metallic stents (SEMSs) are most commonly used. The efficacy of these stents has been extensively described in distal biliary strictures, but not in hilar biliary strictures. The present study aimed to compare the efficacy of PSs and SEMSs for unresectable malignant hilar biliary strictures. From June 2004 to November 2008, 60 patients were enrolled and prospectively randomized into the PS or SEMS group. The 6-month patency rate was significantly higher in the SEMS group than in the PS group (81 vs. 20%; p = 0.0012). Kaplan–Meier analysis showed significantly longer patency in the SEMS group than in the PS group (p = 0.0002); the 50% patency period was 359 days in the SEMS group and 112 days in the PS group. There was no significant difference in the overall survival period between the PS and SEMS groups (p = 0.2834). The mean number of reinterventions for stent failures was significantly lower in the SEMS group (0.63 times/patient) than in the PS group (1.80 times/patient) (p = 0.0008). The overall total cost for the treatment was significantly lower in the SEMS group than in the PS group (p = 0.0222). SEMSs were associated with a longer patency than PSs in patients with unresectable hilar biliary stricture. SEMSs were also more advantageous in reducing the number of reintervention sessions and the overall treatment cost.

Radiofrequency ablation (RFA) is a promising alternative to hepatic resection for the treatment of hepatocellular carcinoma (HCC) located in the caudate lobe. We evaluated the therapeutic efficacy and safety of RFA for HCC located in the caudate lobe compared with HCC located elsewhere in the liver.Overall, 555 consecutive patients treated by RFA for a single HCC tumor of less than 3 cm diameter, were enrolled in this study, including 20 patients with HCC located in the caudate lobe. Among these 20 patients, HCC was located in the Spiegel lobe in eight patients, in the paracaval portion in another 10 and in the caudate process in two. We evaluated differences in the local recurrence rate and the incidence of complications associated with RFA between the caudate and the non-caudate groups.The 4-year cumulative local recurrence rate after RFA in the caudate group and the non-caudate group was 22.3% and 4.5%, respectively (P 0.001). Multivariate analysis of factors affecting local recurrence demonstrated that tumor size and tumor location (caudate or non-caudate) were independent significant factors. No postoperative complications were observed in the caudate group, whereas 15 patients (2.8%) in the non-caudate group experienced complications related to RFA.We were able to safely treat HCC located in the caudate lobe by RFA. However, there was a high incidence of local recurrence, presumably because of the heat sink effect of the inferior vena cava and the restricted puncture approach. We should pursue a revised method to reduce local recurrence.

当院における維持血液透析患者59名 (男性32名, 女性27名, 平均年齢60.7歳, 平均透析期間4.9年) のHCV-RNAおよびそのgenotype, HCV抗体 (第二世代抗体, C100-3抗体, N14抗体, GOR抗体) を測定し, 年齢, 性, 基礎疾患, 透析歴, 輸血歴, 手術歴, 家族歴, 肝疾患の既往, 肝障害の有無, HBc抗体との関連について多変量解析を用いて検討した. HCV-RNA陽性率は初回測定では20.3% (12/59), 第二世代抗体陽性率は45.8% (27/59), C100-3抗体陽性率は16.9% (10/59), N14抗体陽性率は30.5% (18/59), GOR抗体陽性率は25.4% (15/59) であった. HCV-RNA陽性者はすべて第二世代抗体陽性であったが, その他の抗体は必ずしも陽性を示さなかったことより, HCV感染のスクリーニングには第二世代抗体が最も適切であると考えられた.また, このうち37名において6か月後に第二世代抗体とHCV-RNAの再検査を行ったところ, 第二世代抗体陽性, HCV-RNA陰性であった5名のHCV-RNAが陽性化し, HCV-RNAは時期をおいて複数回測定することが望ましいと考えられた. さらに, 第二世代抗体, HCV-RNAともに陰性より両指標とも陽性化を認め, 新規感染を疑わせる1例を経験した. この時点におけるHCV-RNA陽性者は17名であり, このうち測定し得たgenotypeはII型が12例, II+III型が1例, III型が2例であった.第二世代抗体陽性者は90%以上に輸血歴を認め, 透析期間も抗体陰性者に比して有意に長期であったが過去6か月間のGPT異常の頻度には有意差を認めなかった. 第二世代抗体陽性に関する多重ロジスチックモデルを用いた多変量解析では第一に透析歴が, 第二に輸血歴が有意に関与していた.以上から, 第二世代抗体によるスクリーニングおよびより注意深い観血的操作により, 水平感染を予防する必要があると考えられた.

Japan Aerospace Exploration Agency (JAXA) is now under planning on the mission of Data Relay Test Satellite(DRTS) follow-on that named as the DRTS-2 temporarily. The overview of DRTS-2 data relay communication is introduced with the expansion for Kaband higher data rate from DRTS. The Ka-band high data transmission tests are performed and the test results are verified to be able to realize for 800Mbps high data transmission.

Celiac plexus neurolysis (CPN) is an established treatment for upper abdominal cancer pain. Recently, endoscopic ultrasound-guided CPN (EUS-CPN) was introduced and has enabled the performance of CPN under real-time imaging guidance, thereby making this technique much safer and easier. However, this procedure is not always efficacious, and a limited number of patients benefit from it. It should not be recommended for patients suspected of having unfavorable outcomes. We determined the predictive factors for response to EUS-CPN in order to enable rational selection of the therapeutic strategy.Forty-seven consecutive patients who underwent EUS-CPN at our institutions were eligible for this study. Absolute ethanol containing a contrast medium was injected just above the origin of the celiac trunk from the aorta under real-time EUS guidance, and abdominal computed tomography was performed immediately after the procedure to evaluate the distribution of the injected ethanol. The efficacy in pain relief was evaluated based on the pain score at day 7 after EUS-CPN.Pain relief was obtained in 32 patients (68.1%). Multivariate analysis using a multiple logistic regression model revealed that direct invasion of the celiac plexus and distribution of ethanol only on the left side of the celiac artery were significant factors for a negative response to EUS-CPN (odds ratio = 4.82 and 8.67, P = 0.0387 and 0.0224, respectively).EUS-CPN seems to be less effective in patients with direct invasion of the celiac plexus. Ethanol should be injected on both sides of the celiac axis to obtain greater pain relief.

A study was conducted to investigate alterations in the clearance rate of chylomicron remnant from plasma in patients with liver cirrhosis and idiopathic portal hypertension. Chylomicron remnant was labeled with retinyl palmitate which was orally administered at a dose of 0.14 mg/kg body weight. Blood samples were drawn serially up to 6 h after the oral administration, and plasma retinyl palmitate levels were determined by high performance liquid chromatography. Kinetics of plasma disappearance curves of retinyl palmitate were analyzed assuming a three compartment model which consists of chylomicron, chylomicron remnant and low density lipoprotein (LDL) pools. Retinyl palmitate was found to be removed from plasma through the latter two compartments, which fractional efflux rate constants were designated as 12 and 13, respectively. 12 was reduced significantly in both liver cirrhosis (1.4 × 10 −2 /min, median, n = 30) and idiopathic portal hypertension (3.1 × 10 −2 , n = 5) as compared with the control (4.0 x 10 −2 , n = 6).13 in idiopathic portal hypertension (6.8 × 10 −3 /min) was significantly elevated, while that in liver cirrhosis (1.9 × 10 −3 ) was decreased when compared to the control (5.0 × 10 −3 ). Such opposite alterations in l 3 may be brought about by the decrease in the number of the responsible receptor (possibly apoB/E receptor) in liver cirrhosis and by the up-regulation of the receptor in idiopathic portal hypertension. The alterations in l 3 are also suggested to help distinguish idiopathic portal hypertension from liver cirrhosis.

症例は78歳,男性.右季肋部痛を主訴に来院した.初診時,胸腹部X-Pにて右肩・肝・脾・腹腔内リンパ節に異常なX線高吸収影を認め,また腹部超音波検査にて胆石,および肝腫瘍を指摘された.22歳時に右肩腫瘍に対して放射線治療を受けており,この時注入されたトロトラストが関与した肝腫瘍と考えられたが,入院後敗血症,DICを合併し,第27病日急性呼吸不全にて死亡した.剖検にて,死因は肝血管肉腫肺転移巣からの出血による呼吸不全と診断された.また,甲状腺癌の合併もみられた.

Efficacy and safety of double filtration plasmapheresis (DFPP) for chronic hepatitis C were prospectively analyzed in Japanese clinical settings. All patients who received DFPP in combination with interferon (IFN) therapy for chronic hepatitis C were serially recruited at 36 institutions between April 2008 and July 2009 in Japan. A total of 239 patients were analyzed for the safety of DFPP and 206 patients for the efficacy. Of the 206 patients, 181 patients were treated with DFPP in combination with pegylated interferon plus ribavirin (PEG-IFN/RBV + DFPP). Among the 181 patients, 60 patients (33.1%) were treatment-naïves, 35 (19.3%) relapsers and 62 (34.3%) non-responders. Complete early virological response (cEVR) in patients treated with PEG-IFN/RBV + DFPP was achieved in 57.5% overall, 70.0% in treatment-naïves, 57.1% in relapsers and 41.9% in non-responders. In patients with previous PEG-IFN/RBV therapy, cEVR were found in 63.0% of relapsers and 18.9 % of non-responders, and cEVR in patients with other than PEG-IFN/RBV therapy as previous IFN therapy, relapsers and non-responders was 37.5% and 76.0%, respectively. Adverse events were found in 55 patients (23.0%). Serious adverse events were found in four patients (1.7%) who showed puncture-site injury. Adverse events were related to female sex, but not related to age, and DFPP could be performed safely. The cEVR results in this study suggest that high rates of sustained virological response can be achieved in retreated and treatment-naïve patients using DFPP in combination with PEG-IFN/RBV therapy. Results indicate that this therapy could be safely conducted, even in elderly patients.

The efficacy and prognosis with neoadjuvant chemotherapy(NAC)for advanced gastric cancer were assessed by histopathological examination of resected tumors. The subjects consisted of cases (or =75 y.o.) having type 4/large type 3 (diameteror = 8 cm) gastric cancer curable by resection based on preoperative imaging diagnostics. The NAC regimen consisted of oral S-1 at 80-120 mg/body on Days 1-21 and CDDP at 60 mg/m2 on Day 8. After two courses, gastrectomy with D2 or more extended lymph node dissection was performed. Based on histopathological effect grading of resected tumors, patients were classified into responder(grade 2 or above)or nonresponder(grade 1b or below)and analyzed for TS and OPRT gene expressions and prognosis. There were 5 responders and 6 nonresponders. High OPRT expression was mainly associated with responders. On the other hand, high TS expression with low OPRT expression was more frequently associated with nonresponders. At a median follow-up of more than 56 months (minimum follow-up, 54 months; maximum follow-up, 60 months), the 4-year overall survival was 36. 4%. Compared to nonresponders, responders showed a longer survival (p=0. 0864) and relapse-free period (p=0. 0414).These results suggest that NAC with S-1+CDDP is promising against resectable advanced gastric cancer; however, its true value will only emerge after completion of the ongoing phase III study of NAC plus surgery and postoperative chemotherapy for resectable large type 3/type 4 advanced gastric cancer (JCOG0501).

Aim: Several studies have reported that insulin resistance raises the risk of primary hepatocellular carcinoma (HCC). We conducted a prospective, case series study to test the impact of insulin resistance on the recurrence after curative radiofrequency ablation (RFA) of stage I HCC in HCV-positive patients. Methods: From January 2006 to December 2007, 226 consecutive patients underwent treatment for primary HCC at our institutions, including 37 stage I cases. Among them, 33 were HCV-positive, and three, six and 24 received curative surgery, transarterial chemoembolization or RFA, respectively. In the 24 patients treated with RFA, recurrence-free survival was analyzed using the Kaplan–Meier method. The factors contributing to recurrence of HCC were subjected to univariate and multivariate analyses using the Cox proportional hazards model. Insulin resistance was estimated by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Results: Kaplan–Meier analysis showed that the recurrence-free survival was lower in patients with higher HOMA-IR (>2.3, P = 0.0252) or with lower serum albumin level (

A 67-year-old Japanese woman with duodenal Crohn's disease developed cholangitis. Radiographic and endoscopic examinations revealed a marked stenosis of the third portion and a dilatation of the second portion of the duodenum. The endoscopic and histopathological observations showed this disease affected the Vater's papilla. Duodenoscopic manometry indicated a reduced pressure of the phasic sphincter of Oddi, indicating ampullar insufficiency. E. coli was found in the bile culture as the infecting organism. The authors suggest that the cholangitis in this patient was caused by the reflux of duodenal contents into the biliary tract.

劇症肝炎(FH)における糖代謝異常を臨床2病型,予後別に検討した.その結果,入院時の低血糖は急性型(FHA)死亡例では高率(40%)に,一方亜急性型(FHS)死亡例では4.2%のみに,生存例では全く認められなかった.また,低血糖の出現もFHA死亡例では病初期に,FHS死亡例では中～末期に多く認められた.一方,高血糖の頻度はFHA生存例に比し死亡例で顕著で,死亡症例は末期に,生存例では病初期に多く見られた.また,FHではインスリン感受性は良好であり,FHモデルにおいても著明な高インスリン血症が認められたが,IVGTTから求めた糖利用率およびITTによるインスリン感受性は良好であった.FHの栄養管理に際しては臨床病型ならびに肝予備能の程度を十分に念頭にいれて血糖を管理すべきと考えられた.さらに,FHにおける糖処理能,インスリン感受性は良好に保持されていることよりFHに対する高エネルギー輸液療法の有効性,妥当性が裏付けられた.

Current Japanese guidelines recommend that patients should be switched from lamivudine to entecavir when they meet certain criteria. This analysis examines the efficacy and safety of long-term entecavir therapy in patients who were switched to entecavir after 24 weeks' lamivudine therapy in Japanese studies ETV-047 and ETV-060.The Phase II Japanese study ETV-047 assessed the efficacy of different entecavir doses when compared with lamivudine. A total of 33 Japanese patients who received lamivudine 100 mg daily in ETV-047 entered the open-label rollover study ETV-060 and subsequently received treatment with entecavir 0.5 mg daily. Hepatitis B virus (HBV) DNA suppression, alanine aminotransferase (ALT) normalization, hepatitis B e antigen (HBeAg) seroconversion, and resistance were evaluated among patients with available samples for up to 96 weeks. Safety was assessed throughout the treatment period.After 96 weeks of entecavir therapy in ETV-060, 90% of patients achieved HBV DNA400 copies/mL as compared to 21% of patients who completed 24 weeks of lamivudine therapy in ETV-047. Increasing proportions of patients achieved ALT normalization and HBeAg seroconversion following long-term entecavir treatment. No patients experienced virologic breakthrough, and substitutions associated with entecavir resistance were not observed in patients with detectable HBV DNA. Entecavir was well tolerated during long-term treatment.Switching lamivudine-treated patients with chronic hepatitis B to entecavir results in increased virologic suppression with no evidence of resistance through 2 years of entecavir therapy. These findings support recommendations in the current Japanese treatment guidelines that stable lamivudine patients should be switched to entecavir.

Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell neoplasm that develops in a small population of human T-cell lymphotropic virus type 1 (HTLV-1)-infected individuals and is characterize...

The diagnosis of lymphadenopathy after treatment of malignancy is sometimes difficult, especially in patients whose treatment was deemed curative and without local recurrence or those who have increased serum levels of related tumor markers. We aimed to evaluate the effectiveness of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) as a diagnostic tool in patients with lymphadenopathy after curative treatment of malignancy.Consecutive patients with mediastinal, intraabdominal, or pelvic lymphadenopathy after curative treatment of malignancy who were referred to our hospital between October 2003 and September 2007 were enrolled in this study.A total of 62 patients were included. The lymph nodes were located at the mediastinum in 22 patients, intraabdomen in 38 patients, and intrapelvis in 2 patients. From the pathological findings of the FNA sample, 31 patients (50%) were confirmed to have recurrence of the prior malignancy, and 9 patients (15%) were diagnosed as having a different new malignancy. The remaining 22 patients (35%) were shown to have no recurrence or no other malignancies. However, 1 of them was later diagnosed with recurrence by open laparotomy. The overall sensitivity, specificity, accuracy, and positive and negative predictive values of the EUS-FNA were 97%, 100%, 98%, 100%, and 97%, respectively.Lymphadenopathy after treatment of malignancy is not a definitive sign of recurrence. Therefore, pathological sampling and diagnosis are essential for determining the appropriate treatment. For this purpose, EUS-FNA is a safe, convenient, and minimally invasive procedure with high diagnostic value.

To expand the criteria of immune thrombocytopenic purpura (ITP), which is a diagnosis of exclusion, we analyzed proteins separated by 1-dimensional gel electrophoresis of the retained fraction in a Con A-Sepharose column from ITP patients' sera.Serum samples were from 19 adult patients with chronic ITP, 9 patients with thrombocytopenia of decreased production, and 20 healthy controls. Samples were applied to a Con A-Sepharose column, and the retained fraction was subjected to 10% SDS-PAGE. The % area of each densitometric protein peak was compared between the two groups and proteins in each band were identified using LC-MS/MS.Eleven protein bands were distinctly separated by 1-dimensional electrophoresis. The percent area of bands #2 and #3 were significantly higher in ITP patients than in controls. The percent area of band #2 (p0.01) was significantly higher in ITP patients than in non-ITP patients. We identified alpha(2)-macroglobulin, ceruloplasmin (Cp), and C3 in band #2 and complement factor B in #3 band. Serum concentrations of alpha(2)-macroglobulin and Cp were significantly higher in ITP patients than in controls. Serum concentrations of Cp were significantly higher in ITP patients than in non-ITP patients (p=0.0005). Serum complement factor B concentrations were significantly higher in ITP patients and non-ITP patients than in controls. ROC analysis showed that the total percent area of bands #2 and #3, and Cp had higher diagnosis availability for ITP patients when compared with controls and non-ITP patients, respectively.Measurement of Cp separated by the present method could be useful for the diagnosis of ITP in the presence of thrombocytopenia and a non- or low-inflammatory state.

Aim: The efficacy and safety of double filtration plasmapheresis (DFPP) plus interferon (IFN) combination therapy were compared with those of IFN therapy alone in 193 chronic hepatitis C patients having a high hepatitis C virus ribonucleic acid load of difficult-to-treat genotype 1b. Methods: All patients received either interferon alpha-2b (IFN-α-2b) monotherapy or combination therapies with ribavirin and IFN-α-2b or pegylated interferon alpha-2b (PEG-IFN-α-2b). Each patient individually decided whether to receive concomitant DFPP. DFPP was immediately followed by IFN treatment, and up to five sessions were given during the first week. Results: Sixty patients decided to receive DFPP. In the DFPP plus PEG-IFN-α-2b therapy group (n = 30), viral load reduction at 4 weeks after the start of treatment was greater than innon-DFPP (n = 74) (2.47 vs 1.52, log, P = 0.010), and the sustained virus response was also higher (77.8% vs 50.0%), even in cases of re-treated patients (relapsers or non-responders to previous IFN therapies). Adverse events, mild and transient, were observed in 38.3% of all DFPP-treated patients. Conclusion: DFPP plus IFN combination therapy produced a great reduction of viral load during the early stage of treatment and achieved a high sustained virus response, suggesting that this combination therapy may be a new modality for chronic hepatitis C patients at difficult-to-treat states.

A 64-year-old male was diagnosed as having autoimmune hemolytic anemia (AIHA) in December 2001. The diagnosis of AIHA was established based on the presence of anemia, hyperbilirubinemia, reticulocytosis, positive Coombs test and serum LDH elevation. Although he received steroid pulse therapy, disturbance of consciousness appeared and the anemia and icterus did not improve. Plasma exchange was carried out to eliminate antibodies as an emergency measure. The patient's symptoms were ameliorated following four courses of plasma exchange. This case represents a case of aggressive AIHA with disturbance of consciousness and refractory to conventional corticosteroid therapy. Plasma exchange rapidly led to complete remission.

Patients with chronic liver disease (CLD) often develops glucose intolerance. We explored the prevalence of diabetes mellitus in viral CLD, and analyzed factors profoundly affecting the diabetic angiopathies. 229 CLD patients (124 chronic hepatitis and 105 liver cirrhosis) entered the study. The diagnosis of diabetes was made with the criteria by World Health Organization. Laboratory investigation included serum asparate aminotransferase, alanine aminotransferase, albumin, fasting blood sugar, hemoglobin A1c (HbA1c), fasting immunoreactive insulin, and HOMA-R (FBS*IRI/405). The incidence of macro- and microangiopathy were also examined. Forty (17.5%) CLD patients were diagnosed diabetes, giving a significantly higher incidence than that of general cohort (5.3%) (p

To facilitate more economical medical care, we carried out a prospective study of whether a THP-COP regimen (cyclophosphamide, pirarubicin, vincristine, and prednisolone) with low-dose granulocyte colony-stimulating factor (G-CSF) would effectively treat non-Hodgkin's lymphoma (NHL). From April 2003 through March 2004, we enrolled 19 consecutive patients with newly diagnosed NHL treated at our hospital. The patients were divided into young and elderly groups. Each patient underwent chemotherapy with 8 courses of a THP-COP regimen with a 50-microg dose of lenograstim. Age- and sex-matched historical control patients (n = 141) received NHL diagnoses between 1998 and 2003. Each patient in the control group underwent the same chemotherapy and received a 100-microg dose of lenograstim. The mean (+/-SD) total amounts of G-CSF per cycle of chemotherapy were 332 +/- 103 microg (young patients) and 345 +/- 128 microg (elderly patients) in the low-dose group and 594 +/- 439 microg (young) and 730 +/- 551 microg (elderly) in the control group. The duration of fever in 1 cycle of chemotherapy was 0.3 +/- 1.0 days (young) and 0.1 +/- 0.8 days (elderly) in the low-dose group and 0.5 +/- 1.3 days (young) and 0.8 +/- 2.0 days (elderly) in the control group. A THP-COP regimen with low-dose G-CSF could be administered to NHL patients with safety. Administration of a 50-microg dose of lenograstim is sufficient and recommended for the treatment of NHL.

We report a rare case of follicular lymphoma which rapidly showed transformation to the Burkitt type of lymphoma after a treatment consisting of chemotherapy and irradiation. A 51-year-old male visited our hospital in August 2000 because of bilateral neck lymphadenopathy. He was diagnosed as having follicular lymphoma (grade 2) (clinical stage IIIA) with complex karyotypic abnormalities involving t(14 ; 18)(q32 ; q21) and CD20 expression. Initially he was followed as an outpatient without chemotherapy. Six months later, he was admitted because of hydronephrosis due to an intrapelvic tumor. He underwent chemotherapy with 4 courses of CHOP regimen following irradiation therapy and a partial response was obtained. Four months after initiation of the treatment, his disease recurred with numb chin syndrome. Bone marrow aspiration revealed bone marrow involvement by lymphoma cells which had a Burkitt-like appearance. A cytogenetic study using bone marrow blood showed complex abnormalities involving t(8 ; 22)(q24 ; q11) in addition to t(14 ; 18). In spite of salvage chemotherapy, the patient died in September 2001.

This study was conducted to assess therapeutic results following neoadjuvant chemotherapy (NAC) for large type 3/type 4/Bulky N 2 advanced gastric cancer having a poor prognosis following resection. The subjects consisted of cases (or = 75 y.o.) having large type 3 (diameteror = 8 cm), type 4 or Bulky N 2 gastric cancer curable by resection based on preoperative imaging diagnostics. The NAC regimen consisted of TS-1 at 80-120 mg/body on days 1-21 p. o. and CDDP at 60 mg/m2 on day 8 divided. Upon completion of two courses of 4 weeks per course, gastrectomy withor = D2 lymph node dissection was carried out on days 21-34. The average age of the subjects was 60.7 years, and the therapy completion rate was 80% (8/10 cases). Five of ten cases were responders diagnosed as grade 2 by histopathological examination of excised specimens (response rate 50%). Two of five responders were histopathologically evaluated as down-staging as a result of NAC (Stage III A--f Stage I A, Stage IV--f Stage I A). Three of the five non-responders have relapsed, and the relapse-free interval was an average 238 days. In the five responders,one has relapsed at 331 days,while the other 4 responders have shown no relapse yet. Although NAC consisting of TS-1 and CDDP is considered to be effective against advanced gastric cancer, a phase III study with surgical treatment only will be necessary to confirm its true value.

Recently, the treatment using biliary stents play an important role to improve the quality of life (QOL) in patients with inoperable malignant biliary obstruction. Long-term patency is preferable, but the convenience of treatment for stent obstruction should also be considered. In this study, we investigated which stent is currently the most appropriate in hilar and extrahepatic bile duct obstruction. In hilar obstruction, metallic stents (MS) had significantly longer patency than plastic tube stents (TS). As for extrahepatic bile duct obstruction, covered MS (CMS) and MS had significantly longer patency than TS. On the other hand, many difficulties occurred when the MS was obstructed. In some of these patients, it was difficult to place the internal drainage again and their QOL was severely impaired. CMS was more convenient because it could be removed when it was obstructed. These results may suggest that MS should be used carefully in the hilar obstruction and that CMS is the best for the treatment of extrahepatic bile duct obstruction.

Genotypes of hepatitis B virus (HBV) were determined in 145 patients with acute hepatitis B from various districts in Japan to establish their geographic distribution and evaluating the influence on the clinical illness and outcome. Genotypes were A in 27 (19%) patients, B in 8 (5%), C in 109 (75%) and mixed with B and C in the remaining one (1%). Genotype A was more frequent in metropolitan than the other areas (21/69 (30%) vs. 6/76 (8%), P < 0.001). On phylogenetic analysis, seven of the nine (78%) HBV/A isolates selected at random clustered with those from Europe and the United States, while the remaining two with those of subgroup A' prevalent in Asia and Africa. Maximum ALT levels were lower (2069 +/- 1075 vs. 2889 +/- 1867 IU/L, P = 0.03) and baseline HBV DNA titers were higher (5.90 +/- 1.45 vs. 5.13 +/- 1.36 log genome equivalents (LGE)/ml, P = 0.002) in patients infected with genotype A than C. Hepatitis B surface antigen persisted longer in patients infected with genotype A than C (1.95 +/- 1.09 vs. 1.28 +/- 1.42 months, P = 0.02). HBV infection became chronic in one (4%) patient with genotype A and one (1%) with genotype C infection. Fulminant hepatic failure developed in none of the patients with genotype A, one (13%) with genotype B and five (5%) with genotype C. The point mutation in the precore region (A1896) or the double mutations in the basic core promoter (BCP) region (T1762/A1764) were detected in none of the patients with genotype A, two (25%) with genotype B and 27 (26%) with genotype C. In conclusion, genotype A is frequent in patients with acute hepatitis B in metropolitan areas of Japan, probably reflecting particular transmission routes, and associated with longer and milder clinical course than genotype C.

The aim of this study was to determine the carrier rate of hepatitis virus in patients with haematological malignancies and the incidence of liver injury in these patients following chemotherapy. From January 1996 to September 2002, we studied 601 consecutive, unselected series of patients with haematological malignancies admitted in our hospital unit (Japan). They consisted of 246 cases of acute leukaemia, 218 non-Hodgkin's lymphoma (NHL), 13 adult T-cell leukaemia, and 124 multiple myeloma. Of these 601 patients, 373 were men and 228 were women; their mean age was 61 yr, with a range from 18 to 89 yr. The prevalences of hepatitis B virus (HBV) and hepatitis C virus (HCV) were 7.3% and 10.1%, respectively, in NHL, both higher than those in acute leukaemia (1.7% and 2.9%, P < 0.005) and in general Japanese population (1.2% and 2.6%). The incidence of post-chemotherapy liver injury in 25 HBV carriers (36.0%) was significantly higher than that in 539 non-hepatitis virus carriers (12.6%, P = 0.003) and 37 HCV carriers (10.8%, P = 0.026). Liver injury in HBV carriers was more often present in patients who had been treated with steroids than in those without steroids (72.7% and 0%, P = 0.013). After lamivudine became available in our institution, the incidence of liver injury in HBV carriers was reduced from 53.3% to 10.0% (P = 0.041). The therapeutic strategy for haematological malignancies in hepatitis virus carriers should be further investigated.

In patients with chronic liver disease (CLD), quality of life is generally accepted as poor, especially for physical function. However, sufficient data regarding erectile function has not been shown in patients with CLD. The international index of erectile function (IIEF) is widely used to assess erectile function, and a short form of the IIEF was recently developed (IIEF-5). Using this questionnaire, we evaluated erectile dysfunction (ED) in patients with CLD.A total of 117 Japanese patients (64 with chronic hepatitis [CH] and 53 with liver cirrhosis [LC]) were analyzed. The etiologies were hepatitis B virus (HBV) in 21, HCV in 94, and non-B non-C in 2. The IIEF-5 and Medical Outcomes Study Short Form 36 (SF-36) were administered to the patients, and biochemical analyses for items serum albumin, prothrombin time, bilirubin, and ammonia were also performed.The incidence of ED was 85% in the total cohort with CLD, 78% in those with CH, and 92% in those with LC (P0.05 between CH and LC). ED was found in 50% of CLD patients under age 50 years, in 79% aged 50-59, and in 100% aged over 60 (P, overall0.001). The scores for ED severity correlated with increasing grades of a modified Child-Pugh classification (P0.05). Simple regression analysis showed age (P0.01), physical function (P0.001), role physical (P0.001), and social functioning (P0.05) on the SF-36, and serum albumin (P0.001) as significant determinants of ED. Multiple regression analysis identified age (P0.001) and serum albumin (P0.001) as independent significant factors that determined ED.These data clearly demonstrate that liver disease is the cause of ED in patients with CLD, and serum protein status could be relevant to this condition in these patients.

Background/Aims: We assessed the usefulness of the Cornell Medical Index (CMI) and electroencephalogram (EEG) in the prediction and early detection of psychoneurological symptoms associated with interferon (IFN) therapy for chronic viral hepatitis. Methods: Forty-eight consecutive patients received IFN for chronic viral hepatitis for 8–24 weeks. CMI was measured before IFN therapy. Serial EEGs were recorded before IFN therapy, 2, 4 weeks, and thereafter every 4 weeks in the therapy. Results: Psychoneurological symptoms including insomnia, depression, and restlessness were seen in 11 (23%) of 48 patients. Five (13%) of 40 patients with CMI I and II and six (75%) of eight with CMI III developed psychoneurological symptoms (P

Data on 334 patients with HCV genotype 1b and high viral levels were extracted from two multicenter double-blind studies conducted in Japan comparing IFN alpha-2b plus ribavirin (n = 209) with IFN alpha-2b alone (n = 125) for 24 weeks. HCV RNA assay was conducted before and 4, 12, and 24 weeks after the start and 4, 12, and 24 weeks after the end of treatment. Both sustained viral response (SVR) rate and relapse rate after the end of treatment were analyzed in relation to baseline viral levels and the time of first disappearance of virus. In the combination treatment group, the percentage of patients who were HCV RNA-negative within 4 weeks decreased with increase in baseline viral levels (i.e. 42%, 15%, and 11% were HCV RNA-negative in the groups exhibiting500, 500 to850, and/=850kcopies/mL, respectively). In the IFN monotherapy group, the response rates were lower at 13%, 15%, and 1%, respectively. Disappearance of virus within 12 weeks after the start of combination treatment was indicative of higher probability of SVR. The risk of relapse was more highly correlated with the timing of initial viral disappearance than with baseline HCV levels; it was 4.8 and 10.3 times higher in patients who became HCV-negative at 4-12 and 13-24 weeks compared with in those who were HCV-negative within 4 weeks.

A 66-year-old man was admitted to our hospital with epigastralgia. Preoperative examinations revealed an 8.0 x 8.0-cm, Borrmann type 2 tumor in the posterior wall of the cardia, without distant metastases. Total gastrectomy with pancreato-splenectomy and regional lymph node dissection was performed curatively. Histologically, the tumor was composed mainly of small cells with hyperchromatic nuclei and scant cytoplasm, which showed positive staining for Grimelius, gamma-neuron-specific enolase (gamma-NSE), chromogranin A, and serotonin. About 10 months after the operation, a solitary tumor was revealed in S8 of the liver by abdominal computed tomography (CT), and it was histologically confirmed by needle biopsy to be a metastasis of the small-cell carcinoma from the stomach. Instead of hepatectomy, percutaneous microwave coagulating therapy (PMCT) was indicated, because of the patients' liver dysfunction (ICG R15, 39.9%); CT showed complete necrosis of the metastatic focus in the liver after the PMCT. Now, 33 months after the first detection of the liver metastasis (43 months after the gastrectomy), the patient is still alive without any growth of the liver metastasis. The 67 previously reported cases of small-cell carcinoma of the stomach in Japan, including ours, are also reviewed.

Objective Balloon-occluded retrograde transvenous obliteration (B-RTO) has recently been introduced as a new interventional modality to prevent fatal bleeding from solitary gastric varices. A large portal-systemic shunt including gastric varices also causes severe encephalopathy in some cirrhotic patients. In this study, we evaluated the effect of B-RTO as a candidate therapeutic method to treat chronic recurrent hepatic encephalopathy due mainly to a portal-systemic shunt. Patients and Methods Since July 1995, we experienced 43 cirrhotic patients with chronic reccurent hepatic encephalopathy. Among them, six patients had anigographically proven large (>1 cm in diameter) portal-systemic shunt, and received B-RTO. B-RTO was carried out only once using 5% ethanolamine oleate with iopamidole to obliterate the portal-systemic shunt for 30 minutes. The median observation period after B-RTO was 29 months (range 23-46 months). Results In all 6 patients, encephalopathy had disappeared after B-RTO, and the patients were free of encephalopathy during the following 6 months. B-RTO significantly reduced blood ammonia levels at one month, 3 months, and 6 months later, without affecting serum aspartate aminotransferase activity, total bilirubin and albumin concentrations, and plasma prothrombin time. Encephalopathy relapsed in 4 patients between 6 and 30 months. Additional B-RTO was required and effective in 2 of them. Conclusion B-RTO is an effective treatment for chronic recurrent hepatic encephalopathy with an angiographically proven portal-systemic shunt.(Internal Medicine 40: 688-691, 2001)