Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease in industrialized countries worldwide, and has become a serious public health issue not only in Western countries but also in many Asian countries including Japan. Within the wide spectrum of NAFLD, nonalcoholic steatohepatitis (NASH) is a progressive form of disease, which often develops into liver cirrhosis and increases the risk of hepatocellular carcinoma. In turn, a large proportion of NAFLD/NASH is the liver manifestation of metabolic syndrome, suggesting that NAFLD/NASH plays a key role in the pathogenesis of systemic atherosclerotic diseases. Currently, a definite diagnosis of NASH requires liver biopsy, though various noninvasive measures are under development. The mainstays of prevention and treatment of NAFLD/NASH include dietary restriction and exercise; however, pharmacological approaches are often necessary. Currently, vitamin E and thiazolidinedione derivatives are the most evidence-based therapeutic options, although the clinical evidence for long-term efficacy and safety is limited. This practice guideline for NAFLD/NASH, established by the Japanese Society of Gastroenterology in cooperation with The Japan Society of Hepatology, covers lines of clinical evidence reported internationally in the period starting from 1983 to January 2012, and each clinical question was evaluated using the GRADE system. Based on the primary release of the full version in Japanese, this English summary provides the core essentials of this clinical practice guideline comprising the definition, diagnosis, and current therapeutic recommendations for NAFLD/NASH in Japan.(AU)

Involvement of free radicals and oxidative stress in NAFLD/NASH.

Non-alcoholic fatty liver disease (NAFLD) is now the most common liver disease affecting high proportion of the population worldwide. NAFLD encompasses a large spectrum of conditions ranging from fatty liver to non-alcoholic steatohepatitis (NASH), which can progress to cirrhosis and cancer. NAFLD is considered as a multifactorial disease in relation to the pathogenic mechanisms. Oxidative stress has been implicated in the pathogenesis of NAFLD and NASH and the involvement of reactive oxygen species (ROS) has been suggested. Many studies show the association between the levels of lipid oxidation products and disease state. However, often neither oxidative stress nor ROS has been characterized, despite oxidative stress is mediated by multiple active species by different mechanisms and the same lipid oxidation products are produced by different active species. Further, the effects of various antioxidants have been assessed in human and animal studies, but the effects of drugs are determined by the type of active species, suggesting the importance of characterizing the active species involved. This review article is focused on the role of free radicals and free radical-mediated lipid peroxidation in the pathogenesis of NAFLD and NASH, taking characteristic features of free radical-mediated oxidation into consideration. The detailed analysis of lipid oxidation products shows the involvement of free radicals in the pathogenesis of NAFLD and NASH. Potential beneficial effects of antioxidants such as vitamin E are discussed.

Correlation of circulating dehydroepiandrosterone with activated protein C generation and carotid intima-media thickness in male patients with type 2 diabetes.

AIMS: Dehydroepiandrosterone exerts a protective effect against cardiovascular diseases. However, the relationship of dehydroepiandrosterone with the anticoagulant factor activated protein C, generated by the thrombin-thrombomodulin complex on vascular endothelial cells, remains unknown. This study aimed at studying the relationship between dehydroepiandrosterone and activated protein C generation in patients with Type 2 diabetes. METHODS: Sixty-two male patients with Type 2 diabetes were enrolled in this study. Data obtained from 40 healthy male subjects were used as controls. The plasma levels of dehydroepiandrosterone, the activated protein C-protein C inhibitor complex, high-sensitivity C-reactive protein and monocyte chemoattractant protein-1 were measured by enzyme immunoassays. Carotid intima-media thickness was measured by ultrasonography. RESULTS: The plasma levels of dehydroepiandrosterone (5.15 ± 2.81 vs. 3.76 ± 2.16 ng/ml; P < 0.005) and the activated protein C-protein C inhibitor complex (1.90 ± 1.07 vs. 1.02 ± 0.51 ng/ml; P < 0.001) were significantly lower in patients with diabetes than in normal subjects. Univariate analysis showed a significant correlation of the plasma level of dehydroepiandrosterone with that of the activated protein C-protein C inhibitor complex (r = 0.48, P < 0.001), high-sensitivity C-reactive protein (r = -0.30, P < 0.05) and with the mean intima-media thickness (r = -0.28, P < 0.05) in patients with diabetes. Stepwise multiple regression analysis showed that the plasma level of dehydroepiandrosterone is significantly correlated with the plasma levels of the activated protein C-protein C inhibitor complex (F = 18.06) and high-sensitivity C-reactive protein (F = 4.94). There was no correlation between the plasma levels of dehydroepiandrosterone and monocyte chemoattractant protein-1. CONCLUSIONS: These results suggest that lower circulating levels of dehydroepiandrosterone are associated with decreased activated protein C generation and higher intima-media thickness in patients with Type 2 diabetes.

Carotid artery calcification and atherosclerosis at the initiation of hemodialysis in patients with end-stage renal disease.

AIMS: Vascular calcification and atherosclerosis frequently develop in end-stage renal disease (ESRD). Although several reports have investigated both carotid artery calcification (CAAC) and carotid atherosclerosis in ESRD patients, the relationship between the two vascular conditions has remained unclear. The aim of this study was to assess the prevalence of CAAC and carotid artery plaque (CAP) in patients with ESRD and to investigate potential factors contributing to the development of CAAC and CAP. MATERIAL AND METHOD: This cross-sectional study assessed CAAC and CAP using multidetector computed tomography and high-resolution B-mode ultrasonography, respectively, in 135 patients with ESRD at the start of hemodialysis. The prevalence of CAAC and CAP was examined. The risk factors associated with CAAC and CAP were also evaluated using a logistic regression model. RESULTS: CAAC and CAP were found in 71% and 65%, of the patients, respectively. A logistic regression analysis adjusted for age and gender showed that CAAC was significantly associated with age, hypertension, dyslipidemia, serum albumin, calcium-phosphorus product, proteinuria and CAP. In contrast, in the same analysis, CAP was significantly correlated with age, male gender, diabetes, intact parathyroid hormone, proteinuria and CAAC. In the multivariate analysis, CAAC was independently associated with age, hypertension, and calcium-phosphorus product. Male gender was identified as an independent determinant for CAP. Furthermore, CAP remained as an independent risk factor of CAAC (odds ratio (OR): 13.89; 95% confidence interval (CI): 4.08-47.29), and CAAC also showed a high OR for having CAP (OR: 11.74; 95% CI: 4.12-33.51). CONCLUSION: Both CAAC and CAP were associated with traditional and/or non-traditional risk factors. The risk factors of CAAC were different from those of CAP. CAAC or CAP was identified to be an independent risk factor for each other with a high OR, thus suggesting a strong relationship between carotid calcification and atherosclerosis.

Different profiles of circulating angiogenic factors and adipocytokines between early- and late-onset pre-eclampsia.

OBJECTIVE: Circulating angiogenic factors have been shown to be important in the pathophysiology of pre-eclampsia. Blood levels of adipocytokines differ in pre-eclampsia relative to controls and may also play an important role in disease pathogenesis. Differences in the circulating levels of these molecules were compared between matched normotensive controls and women with pre-eclampsia with onset before or at/after 32 weeks, and according to whether the women were of normal weight (18.5 < body mass index < 25) or overweight. DESIGN: A cross-sectional study of 110 pregnant Japanese women who visited the Department of Obstetrics and Gynecology, Okayama University Hospital, Okayama, Japan. SETTING: Tertiary referral centre serving 2000 births. METHODS: Serum concentrations of soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), soluble endoglin (sEng), adiponectin and leptin were measured in women with pre-eclampsia and in normotensive controls matched for age, gestational week, parity and body mass index. Main outcome measures Serum levels of sFlt-1, PlGF, the sFlt-1/PlGF ratio, sEng, adiponectin and leptin. RESULTS: The sFlt-1/PlGF ratio in early-onset pre-eclampsia was significantly higher than that in late-onset pre-eclampsia (112.0 +/- 30.2 versus 45.4 +/- 43.8, P = 0.037). There was a significant elevation of leptin in both subtypes relative to controls (early: 58.6 +/- 18.3 ng/ml versus 26.0 +/- 6.7 ng/ml, P = 0.001; late: 39.5 +/- 9.2 ng/ml versus 22.0 +/- 4.3 ng/ml, P = 0.005), but adiponectin was increased only in late-onset pre-eclampsia (36.5 +/- 13.4 microg/ml versus 12.0 +/- 4.3 microg/ml, P = 0.003). Significant differences in angiogenic factors and adiponectin were found between normal and overweight women only in late-onset pre-eclampsia. CONCLUSIONS: These data suggest that there are different profiles of angiogenic factors and adipocytokines between women who develop early- and late-onset pre-eclampsia.

Endoscopic submucosal dissection for colorectal tumors: technical difficulties and rate of perforation.

BACKGROUND AND STUDY AIM: Endoscopic submucosal dissection (ESD) for colorectal tumors is not generally recommended because of the technical difficulties and complications, including perforation. These aspects of ESD are thoroughly analyzed in our retrospective study. PATIENTS AND METHODS: We studied 105 colorectal tumors, from 100 patients, that were treated by ESD at the Kyoto Prefectural University of Medicine or Nara City Hospital between 2005 and 2008. We analyzed tumor size, operation time, rate of en bloc resection, and complications. In addition, we thoroughly investigated the cases of perforation. RESULTS: The average tumor size was 30.4 mm; average operation time, 102 min; and rate of en bloc resection, 88.5 %. Perforation occurred in 10.4 % of the ESD procedures. Of the 11 perforations, 8 were detected during ESD and treated by clip closure during endoscopy, while 3 were evident only on subsequent routine computed tomography (CT); these were also managed conservatively. A case of postoperative hemorrhage was also observed. CONCLUSIONS: ESD effectively achieved a high rate of en bloc resection. However, the perforation rate was substantial; hence, improvement in the ESD method is required. The outcomes of ESD, especially for early colorectal malignancies, need to be assessed further.

Impact of double-balloon endoscopy on the diagnosis of jejunoileal involvement in primary intestinal follicular lymphomas: a case series.

In recent years, primary gastrointestinal follicular lymphoma has been increasingly detected in the duodenum on esophagogastroduodenoscopy (EGD). Primary gastrointestinal follicular lymphomas are frequently distributed to multiple sites in the gastrointestinal tract. Therefore, investigation into the spread of follicular lymphomas in the small bowel is important in order to determine the most appropriate treatment strategy. The performance of double-balloon endoscopy (DBE) in the diagnosis of jejunoileal follicular lymphoma lesions has not been fully evaluated. We aimed to investigate the value of DBE in addition to computed tomography (CT) and (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) in the diagnosis of jejunoileal follicular lymphoma. DBE with biopsy was performed in seven patients with primary duodenal follicular lymphoma diagnosed by EGD, in order to investigate jejunoileal involvement. Jejunoileal follicular lymphoma lesions were detected by DBE in six out of the seven patients (three in the jejunum and three in the jejunum and ileum), whereas CT and (18)F-FDG-PET failed to detect the existence of these lesions. Endoscopic findings of the jejunoileal lesions revealed multiple white nodules and white villi, which were similar to those of duodenal lesions. DBE was more useful for the diagnosis of jejunoileal involvement in primary intestinal follicular lymphoma than CT and (18)F-FDG-PET. The use of DBE will become important for determining the most appropriate treatment for gastrointestinal follicular lymphoma.

Trisectionectomy for large hepatocellular carcinoma using the liver hanging maneuver.

BACKGROUND/PURPOSE: Large liver tumors often expand and severely compress intrahepatic vessels. In cases of the trisectionectomy for such tumors, however, it is difficult to adequately expose the transection planes. The liver hanging maneuver (LHM) is a useful technique for hemihepatectomy and an adequate transection plane might be also required in trisectionectomy. METHODS: LHM procedure is basically followed by the Belghiti's method. A nasogastric tube was used for hanging. At the hepatic hilum, the tube was placed between the liver and Glisson's pedicle. RESULTS: We report here the application of LHM for right and left trisectionectomy in patients with a large hepatoma in two cases. In case of a right trisectionectomy for a large tumor compressing the umbilical Glisson's pedicle, an adequate transection plane was obtained using the LHM because the resected and remnant livers rotated to the other side upon lifting the tube during transection. In case of a left trisectionectomy for a large hepatic tumor compressing the right hepatic vein, an adequate transection plane along the right hepatic vein was obtained using LHM as well. CONCLUSIONS: LHM is a useful surgical application for right and left trisectionectomy in patients with large liver tumors compressing the cut plane.

Comparison of survival between anatomic and non-anatomic liver resection in patients with hepatocellular carcinoma: significance of surgical margin in non-anatomic resection.

AIMS: Anatomic resection, i.e., systematic removal of a liver segment confined by portal branches, is theoretically effective in eradicating intrahepatic metastasis of hepatocellular carcinoma (HCC). The procedure may reduce tumour recurrence and enhance survival of HCC patients. To determine the significance of anatomic resection for HCC patients, we retrospectively conducted a comparative analysis between anatomic (AR) and non-anatomic liver resection (NAR) in 113 Japanese HCC patients with a solitary tumour, a tumour located within one segment, absence or invasion of distal to second order branches of the portal vein, and absence or invasion of peripheral branches of the hepatic vein. METHODS: Patients were divided into two groups, AR group (n = 49) and NAR group (n = 64). RESULTS: The prevalence of liver damage Grade B in the NAR group was significantly greater than in the AR group (p < 0.05). Tumour-free and overall survival following liver resection was not significantly different between AR and NAR groups. In the NAR group, tumour-free and overall survival in patients with tumour exposure at the surgical margin was significantly lower than with a surgical margin greater than 0 mm (not exposed) (p < 0.05). Survival between the AR and NAR groups without tumour exposure at the surgical margin was similar. CONCLUSIONS: Anatomic resection is the theoretical aim. In HCC patients with impaired liver functions, limited liver resection without tumour exposure may provide longer tumour-free and overall survival.

Preparation of functionally preserved CD4+ CD25high regulatory T cells from leukapheresis products from ulcerative colitis patients, applicable to regulatory T-cell transfer therapy.

BACKGROUND: Ulcerative colitis (UC) is an intractable disease; therefore new therapies need to be developed. CD4(+) CD25(high) regulatory T cells (Treg) significantly ameliorate colitis in animal models. In active UC patients, although Treg are functionally preserved, their proportion in peripheral blood decreases. Thus Treg transfer therapy is expected to be efficacious for UC. During leukapheresis for UC, Treg are depleted, as well as colitogenic effector leukocytes. We therefore designed a leukapheresis/Treg transfer therapy in which Treg are isolated from leukapheresis products and transfused to patients, and studied large-scale germ-free methods of Treg preparation. METHODS: Using the CliniMACS cell selection system, we conducted Treg isolation experiments from leukapheresis products in which B and CD8(+) T cells were depleted, followed by positive selection of CD25(+) cells. In some experiments, isolated Treg or non-Treg were expanded with interleukin-2 (IL-2) +/- transforming growth factor (TGF)-beta1. Expression of a Treg-specific marker, FOXP3, and gut-homing receptors, and suppressor activity of isolated or cultured cells, were analyzed. RESULTS: CD4(+) CD25(high) T cells were collected and efficiently enriched with a good recovery rate. Isolated cells preferentially expressed FOXP3 and significantly suppressed T-cell proliferation in vitro. In addition, isolated Treg could be efficiently expanded, and Treg could be induced from non-Treg with TGF-beta1 in vitro. TGF-beta1 significantly up-regulated alphaEbeta7 and alpha4beta7 integrins. DISCUSSION: We have established a method of Treg isolation from leukapheresis products that can be used clinically; therefore, Treg transfer therapy is feasible in combination with leukapheresis for UC. Expansion or induction of Treg in vitro may be another approach to Treg-based immunotherapy.

Protective role of thrombin activatable fibrinolysis inhibitor in obstructive nephropathy-associated tubulointerstitial fibrosis.

BACKGROUND: Thrombin-activatable fibrinolysis inhibitor (TAFI) has been reported to affect wound healing and fibrotic processes, but its role in renal tubulointerstitial fibrosis remains unknown. OBJECTIVE: To study its potential role, we compared TAFI-deficient and wild-type mice for the degree of renal fibrosis caused by unilateral ureteral obstruction (UUO). METHODS: The grade of tubulointerstitial fibrosis, the activity of plasmin, MMP-2 and MMP-9 were evaluated on days 4 and 9 after UUO. RESULTS: The renal content of hydroxyproline and the activity of plasmin, MMP-2 and MMP-9 were significantly increased in kidneys with UUO from TAFI-deficient mice compared with those from wild-type mice. These differences disappeared when animals with UUO from both groups were treated with the plasmin inhibitor tranexamic acid. The renal concentrations of fibrogenic cytokines were also significantly elevated in kidneys with UUO from TAFI-deficient mice compared with those from wild-type mice. CONCLUSION: The results of this study suggest that increased renal activity of plasmin in TAFI-deficient mice causes increased renal interstitial fibrosis in obstructive nephropathy.

Inverse correlation between activated protein C generation and carotid atherosclerosis in Type 2 diabetic patients.

AIMS: Activated protein C (APC) is a key regulator of the clotting system and immune responses. We studied the relationship between the degree of atherosclerosis as measured by the intima-media thickness (IMT) of carotid artery and APC generation in Type 2 diabetic patients. METHODS: Eighty-seven Type 2 diabetic patients and 35 control subjects participated. APC generation was assessed by the plasma APC-protein C inhibitor complex (APC-PCI) levels and the mean IMT of carotid artery was measured by ultrasonography. The plasma levels of the thrombin-anti-thromobin complex (TAT) and platelet-derived growth factor (PDGF) were measured by enzyme-linked immunoassays. RESULTS: Plasma TAT levels were significantly higher in diabetic patients [2.03 (1.12, 2.56) ng/ml, median (25th, 75th percentile)] compared with control subjects [0.85 (0.55, 2.08) ng/ml, P < 0.01]. Plasma APC-PCI levels were significantly lower in diabetic patients [0.93 (0.74, 1.22) ng/ml], than in control subjects [1.66 (1.25, 2.36) ng/ml, P < 0.001]. The mean IMT was significantly increased in diabetic patients (0.881 +/- 0.242 mm; mean +/- sd) compared with control subjects (0.669 +/- 0.140 mm; P < 0.01). Univariate analysis showed a significant and inverse correlation between plasma APC-PCI levels and mean IMT (r = -0.32, P < 0.005), and multivariate regression analysis confirmed the independent correlation (P < 0.05). Moreover, plasma APC-PCI levels significantly and inversely correlated with plasma PDGF levels in diabetic patients (r = -0.30, P < 0.01). CONCLUSIONS: These results suggest that decreased APC generation is associated with vascular atherosclerotic changes in Type 2 diabetic patients.

An increase in the serum amylase level in patients after peroral double-balloon enteroscopy: an association with the development of pancreatitis.

BACKGROUND AND STUDY AIMS: Double-balloon enteroscopy (DBE) is a novel technique that allows the enteroscope to be inserted deep into the small intestine. The procedure has been thought to be safe, but cases of acute pancreatitis after peroral DBE have recently been observed. The aim of this study was to confirm the occurrence of hyperamylasemia after peroral DBE. PATIENTS AND METHODS: Peroral DBE was carried out in 13 patients from July 2005 to February 2006. Blood samples were taken before and 3 h after the procedure, and serum pancreatic amylase levels were measured. The patients were also evaluated for pancreatic-type abdominal pain after the procedure. Hyperamylasemia after peroral DBE was defined as an elevation of the serum pancreatic amylase level to more than the upper normal limit and twice the level before the procedure. Pancreatitis was diagnosed on the basis of both pancreatic-type abdominal pain and hyperamylasemia. RESULTS: Hyperamylasemia after peroral DBE occurred in six patients (46.2 %). One of the six patients with hyperamylasemia had pancreatic-type abdominal pain after the procedure and developed acute pancreatitis. The average procedure time was 105 min (range 65 - 155 min) in the patients with hyperamylasemia, and did not significantly differ from that in the group without hyperamylasemia (99 min). CONCLUSIONS: Hyperamylasemia after peroral DBE occurs frequently and may be associated with development of pancreatitis.

Clinical evaluation of magnetic resonance imaging flowmetry of portal and hepatic veins in patients following hepatectomy.

BACKGROUND: Hepatic blood flow was associated with degree of hepatic damage. Measurements of blood flow using ultrasonography (US) may vary due to any observer's and patient's conditions. The utility of magnetic resonance imaging (MRI) flowmetry in portal and hepatic veins was assessed. PATIENTS AND METHODS: Using the phase-contrast method, the mean flow velocity of portal (PVF) and hepatic vein (HVF) were determined by MRI and US in 75 consecutive patients with liver diseases, including 58 patients undergoing hepatectomy. The correlations between these parameters and clinicopathological findings were examined. RESULTS: PVF and HVF measured by MRI flowmetry were 12.8+/-4.5 and 14.7+/-5.3 cm/s, respectively. There was no significant correlation of both flows between MRI and US. PVF correlated significantly with portal pressure (r = -0.722; P < 0.05). There was a negative correlation between HVF and histological activity index score (r = -0.366; P < 0.05). PVF and HVF were lower in patients with cirrhosis and higher staging score (2-4) and PVF was lower in patients with higher grading score (2-3; P < 0.05). PVF and HVF were not significantly associated with postoperative complications. CONCLUSIONS: Our results suggest that MRI flowmetry is a potentially useful tool for measurement of hepatic blood flow and recommend its use for estimation of liver cirrhosis-associated impairment.

Endoscopic band ligation therapy for upper gastrointestinal bleeding related to Mallory-Weiss syndrome.

BACKGROUND: No consensus exists as to the best endoscopic treatment for Mallory-Weiss syndrome. Endoscopic band ligation is a readily available and easily learned technique. This prospective study evaluated the efficacy and safety of endoscopic band ligation therapy for Mallory-Weiss syndrome. METHODS: From August 1998 to June 2005, a clinical trial assessed 37 patients with a diagnosis of Mallory-Weiss syndrome who had active bleeding, exposed vessels, or both. Their lesions were treated using endoscopic band ligation. RESULTS: Endoscopic band ligation was successful in 36 of 37 cases, with a follow-up period ranging from 1 to 24 months. The remaining patient had severe liver failure and disseminated intravascular coagulation. The patient bled again at 12 h and subsequently died. Except for this case, no recurrent bleeding, perforation, or other complications occurred. CONCLUSIONS: The study results suggest that endoscopic band ligation is an effective, safe, and easily learned procedure for treating upper gastrointestinal bleeding related to Mallory-Weiss syndrome.

Postoperative changes in protein-induced vitamin K absence or antagonist II levels after hepatectomy in patients with hepatocellular carcinoma: relationship to prognosis.

BACKGROUND: alpha-Fetoprotein (AFP) has been used as a marker for hepatocellular carcinoma (HCC). However, AFP levels are often high in patients with chronic hepatitis or cirrhosis. Protein-induced vitamin K absence or antagonist II (PIVKA-II) is more sensitive for the diagnosis of HCC and prediction of patient survival. Changes in these markers after treatment may reflect treatment curability and patient outcome. METHODS: We conducted a retrospective analysis of prognosis of 63 HCC patients with high preoperative levels of AFP and PIVKA-II who underwent hepatectomy and examined the relationship between postoperative changes in both markers at 1 month and patient survival. Subjects were divided into three groups according to changes in these tumour markers after hepatectomy: normalization (N) group, decreased but still above the normal level (D) group and unchanged (U) group. RESULTS: There were no significant differences in the numbers of patients who developed tumour recurrence between changes in AFP and PIVKA-II. Survival analysis showed no significant differences in tumour-free and overall survivals between groups with respect to AFP level. The PIVKA-II-N group showed significantly better tumour-free and overall survival compared with the D and U groups (p<0.01). Multivariate analysis that included other prognostic factors identified changes in PIVKA-II level as a significant and independent prognostic factor associated with overall survival. DISCUSSION: Although changes in AFP did not correlate with patient prognosis, normalization of PIVKA-II was significantly associated with good patient survival after hepatectomy. Normalization of PIVKA-II after hepatectomy reflected the efficacy of treatment and is a suitable predictor of prognosis in HCC patients.

EUS-guided endoscopic resection using band ligation of oesophageal granular cell tumour: report of a case.

A 60-year-old Japanese man was referred for treatment of a polypoid oesophageal tumour. Radiographic examination of the upper gastrointestinal tract disclosed a nodule with central depression in the lower esophagus. By endoscopy the nodule was yellowish and appeared submucosal. Endoscopic ultrasonography demonstrated a hypoechoic solid tumour limited in submucosa without lymph node involvement. Endoscopic resection using band ligation was performed under guidance by endoscopic ultrasonography. By histologic examination the tumour consisted of large cells arranged in nests. These cells had abundant granular cytoplasm and small round nuclei. They expressed S-100 protein and were CD68, and periodic acid-Schiff positive. No expression of alpha-smooth muscle actin was noted. The tumour was limited in submucosa. Findings were consistent with complete endoscopic resection. This report may be the first concerning an oesophageal granular cell tumour successfully treated with EUS-guided endoscopic resection using band ligation.

Comparative study of survival of patients with hepatocellular carcinoma predicted by different staging systems using multivariate analysis.

AIMS: In a previous pilot study, we reported the usefulness of the modified the Cancer of the Liver Italian Program (CLIP) score for patients with hepatocellular carcinoma (HCC). To determine the best staging system for predicting the survival of HCC patients, we conducted a comparative analysis of prognosis using multivariate analysis in 210 Japanese HCC patients who underwent hepatic resection. METHODS: We compared the survival as predicted by various staging systems, including tumour node metastasis (TNM) stage of the American Joint Commission on Cancer (AJCC) and the Liver Cancer Study Group of Japan, the Japan Integrated Staging (JIS) score (Japanese TNM and Child-Pugh classification), CLIP score and our modified CLIP score using protein induced by vitamin K absence or antagonist II (PIVKA-II). RESULTS: Univariate analysis showed that discrimination of disease-free survival in the early and advanced stages by the JIS score and modified CLIP score was clearer than by the Japanese or AJCC TNM or the original CLIP score. Discrimination between stages of overall survival by all staging systems was significant. Multivariate analysis showed that the JIS, CLIP and modified CLIP scores were better staging systems for predicting survival than the Japanese and AJCC TNM. The modified CLIP score showed the lowest Akaike information criteria statistical value for disease-free and overall survival, which means the best discrimination ability for patient survival compared with the JIS score and CLIP score. CONCLUSIONS: A staging system that combines tumour factors, sensitive tumour marker(s) and hepatic function is the best predictor of prognosis of HCC patients.