Simple new clinical score to predict hepatocellular carcinoma after sustained viral response with direct-acting antivirals.

The time point of the most precise predictor of hepatocellular carcinoma (HCC) development after viral eradication with direct-acting antiviral (DAA) therapy is unclear. In this study we developed a scoring system that can accurately predict the occurrence of HCC using data from the optimal time point. A total of 1683 chronic hepatitis C patients without HCC who achieved sustained virological response (SVR) with DAA therapy were split into a training set (999 patients) and a validation set (684 patients). The most accurate predictive scoring system to estimate HCC incidence was developed using each of the factors at baseline, end of treatment, and SVR at 12 weeks (SVR12). Multivariate analysis identified diabetes, the fibrosis-4 (FIB-4) index, and the α-fetoprotein level as independent factors at SVR12 that contributed to HCC development. A prediction model was constructed with these factors that ranged from 0 to 6 points. No HCC was observed in the low-risk group. Five-year cumulative incidence rates of HCC were 1.9% in the intermediate-risk group and 15.3% in the high-risk group. The prediction model at SVR12 most accurately predicted HCC development compared with other time points. This simple scoring system combining factors at SVR12 can accurately evaluate HCC risk after DAA treatment.

Effects of Exercise Therapy and Nutrition Therapy on Patients with Possible Malnutrition and Sarcopenia in a Recovery Rehabilitation Ward.

We compared the effects of an exercise intervention with that of exercise combined with nutrition therapy in patients with possible malnutrition and sarcopenia admitted to a recovery rehabilitation ward, and we examined the differences in the patients' physical function and activities of daily living (ADLs). There were 16 patients in the Exercise group with exercise therapy and ADL exercises, and 14 patients in the Combined intervention group with exercise therapy, ADL exercises, and nutrition therapy. The survey items were body weight, body mass index, grip strength, lower-leg circumference, gait speed, and ADLs, each of which was measured at the baseline and at 2 weeks, 4 weeks, and at discharge. Significant improvements in grip strength were observed in the Combined intervention group as follows: at 4 weeks>at 2 weeks (p<0.05), and at discharge>baseline and 2 weeks (p<0.05). There were no significant changes in the Exercise group, and an interaction was recognized in both groups. Comprehensive rehabilitation including nutrition therapy is necessary for patients with possible malnutrition and/or sarcopenia, as our results indicate that nutrition therapy in addition to exercise therapy has the effect of promoting improvements of physical function in such patients.

AFP and eGFR are related to early and late recurrence of HCC following antiviral therapy.

BACKGROUND: An unexpected recurrence of hepatocellular carcinoma (HCC) sometimes occurs in patients with hepatitis C virus (HCV) after treatment with direct-acting antivirals (DAAs). However, the characteristics of patients with HCC recurrence may differ depending on time after DAA treatment. We aimed to identify risk factors related to HCC recurrence according to time after DAA treatment. METHODS: Of 1663 patients with HCV treated with a DAA, 199 patients had a previous history of HCC. We defined HCC recurrence within 1 year after DAA treatment as 'early recurrence', and recurrence more than 1 year after as 'late recurrence'. The different risk factors between the early and late phases of HCC recurrence after the end of DAA therapy were investigated. RESULTS: Ninety-seven patients experienced HCC recurrence during the study period. Incidences of recurrence were 29.8, 41.0, and 53.4% at 1, 2, and 3 years, respectively, after the end of DAA therapy. Multivariate analysis identified post-treatment α-fetoprotein (AFP) as an independent factor contributing to HCC recurrence in the early phase (hazard ratio, 1.056; 95% confidence interval, 1.026-1.087, p < 0.001) and post-treatment estimated glomerular filtration rate (eGFR) (hazard ratio, 0.98; 95% confidence interval, 0.96-0.99, p = 0.032) as a predictor of HCC recurrence in the late phase. CONCLUSION: Patients with higher post-treatment AFP in the early phase and those with lower post-treatment eGFR in the late phase had a high risk of HCC recurrence. The risk factors associated with HCC recurrence after DAA treatment were different between the early and late phases.

Sex difference in the development of hepatocellular carcinoma after direct-acting antiviral therapy in patients with HCV infection.

Sex differences in the predictors for hepatocellular carcinoma (HCC) development after direct-acting antiviral (DAA) therapy was investigated. DAA therapy was given to 1438 (663 male, 775 female) patients. Sex differences in the HCC development rate and the factors contributing to HCC development after DAA therapy were investigated. Male patients had a significantly higher cumulative HCC incidence (log-rank test, P = .007). On multivariate analysis, the fibrosis-4 index (HR = 1.11; 95%CI, 1.042-1.202, P = .002) and posttreatment α-fetoprotein (AFP) (HR = 1.11; 95%CI, 1.046-1.197, P = .001) were found to be independent factors that contributed to HCC development following DAA therapy in female patients, whereas only posttreatment AFP (HR = 1.090; 95%CI, 1.024-1.160, P = .007) was an independent factor in male patients. The optimal posttreatment AFP cut-off values were set based on receiver operating characteristic curve analyses. The optimal posttreatment AFP cut-off value was much higher in females (6.0 ng/mL) than in male (3.5 ng/mL) patients. In conclusion both in male and female patients, posttreatment AFP was an independent predictor of HCC development after DAA therapy. However, the cut-off values differed between the sexes. In male patients, HCC could be seen in patients with relatively low posttreatment AFP levels; more careful observation might be needed in such patients.

Predictors of hepatocellular carcinoma occurrence after direct-acting antiviral therapy in patients with hepatitis C virus infection.

AIM: The predictors for the development of hepatocellular carcinoma (HCC) after direct-acting antiviral (DAA) treatment were investigated. METHODS: A total of 1174 patients with chronic hepatitis C virus infection were treated with DAA therapy (sofosbuvir and ledipasvir [n = 615], sofosbuvir and ribavirin [n = 380], and daclatasvir and asunaprevir [n = 179]) and achieved sustained virologic response (SVR). The HCC development rate and the factors that might contribute to the development of HCC after the end of DAA treatment were analyzed. RESULTS: During the median observation period of 537 days, HCC developed in 33 cases. The incidence of HCC was 1.9%, 3.2%, and 4.1% at 1, 1.5, and 2 years after the end of DAA therapy, respectively. Multivariate analysis with pre- and post-treatment factors identified the Fibrosis-4 (FIB-4) index (hazard ratio [HR] = 1.09; 95% confidence interval [CI], 1.021-1.178; P = 0.011) and post-treatment α-fetoprotein (AFP) (HR = 1.11; 95% CI, 1.054-1.172; P < 0.001) as independent factors that contributed to the development of HCC after DAA therapy. Using these identified parameters, a new scoring system (0 to 2 points) was established. Patients in the high-score group (2 points) could be identified as having a significantly higher risk of HCC development, and the respective 1- and 2-year cumulative incidence rates of HCC were 6.1% and 14.4%. CONCLUSIONS: A high FIB-4 index and a high post-treatment AFP at the end of DAA treatment were the independent predictors for developing HCC after DAA treatment. For patients with these risk factors, extra attention to the possibility of HCC development is needed.

Familial Pancreatic Cancer at Elderly Siblings in Japan.

Two female siblings aged 87 and 90 years were clinically diagnosed as pancreatic cancer by abdominal ultrasonography and abdominal contrast-enhanced CT. Pancreatic cancer of these patients was confirmed during the autopsy. Both patients shared risk factors of pancreatic cancer; old age, diabetes, and passive smoking. Strong family history of pancreatic cancer was found in these two patients as their father and younger brother were also suffering from this cancer. The present study seems to report two eldest cases of familial pancreatic cancer in siblings. How to cite this article: Kashimoto Y, Onji M, et al. Familial Pancreatic Cancer at Elderly Siblings in Japan. Euroasian J Hepatogastroenterol 2019;9(1):52-54.

Predictors of treatment efficacy and ALT non-normalization with sofosbuvir/ribavirin therapy for patients with hepatitis C virus genotype 2.

The tolerability and efficacy of sofosbuvir and ribavirin in patients infected with hepatitis C virus (HCV) genotype 2 were investigated under actual clinical conditions. A total of 208 patients with chronic HCV genotype 2 infection were treated with sofosbuvir 400 mg and ribavirin (weight-based dosing) for 12 weeks. Treatment discontinuation and sustained virological response 12 (SVR12) were evaluated. Moreover, factors associated with SVR12, hemoglobin decreasing to less than 10 g/dL during treatment, and alanine aminotransferase (ALT) non-normalization after treatment were evaluated. In all patients, SVR12 responses were 96.1% (200/208). About 6 of 8 patients (3.8%) who did not achieve SVR12 were re-treatment patients, and eight patients who did not achieve SVR all had liver cirrhosis. Multivariate analysis also identified body mass index (OR = 0.79; P < 0.001), platelet count (OR = 0.88; P = 0.003), and estimated glomerular filtration rate (eGFR) (OR = 0.96; P = 0.007) as independent contributing factors associated with hemoglobin decreasing to less than 10 g/dL during treatment, and only Mac-2 Binding Protein Glycosylation isomer (M2BpGi) (OR = 2.46; P = 0.017) as an independent contributing factor associated with ALT non-normalization after treatment. Cirrhotic patients may have a relatively high rate of treatment failure. In patients whose M2BpGi levels are elevated, their ALT tended to not normalize after treatment completion. These patients who did not achieve normalization of ALT after sofosbuvir plus RBV treatment need more careful observation for emergence of hepatocellular carcinoma even after achievement of SVR.

Simeprevir with peginterferon/ribavirin for patients with hepatitis C virus genotype 1: high frequency of viral relapse in elderly patients.

PURPOSE: The tolerability and efficacy of simeprevir in combination with peginterferon and ribavirin in patients infected with hepatitis C virus (HCV) genotype 1 under actual clinical conditions were investigated. METHODS: A total of 176 patients with chronic HCV genotype 1 infection were treated with simeprevir for 12 weeks plus Peg-IFN/RBV for 24 weeks. Overall, 107 (60.7 %) patients were aged 60 years or more, and 16 (9 %) patients were aged 70 years or more. Treatment discontinuation, sustained virological response 12 (SVR12), and viral relapse were evaluated and compared between younger patients and elderly patients. RESULTS: The rates of undetectable HCV RNA at the end of treatment were 95.8, 100 and 93.1 % in treatment-naïve, prior relapse, and prior non-responders, respectively. However, the rates of SVR12 were 82.4, 88.2 and 69.2 %, respectively. Especially in prior non-responders, viral relapse was relatively frequent. Treatment discontinuation and SVR12 were not different between patients aged <70 and ≥70 years, but viral relapse after completing treatment was significantly more frequent in patients aged ≥70 years (p = 0.012). CONCLUSIONS: In simeprevir with peginterferon and ribavirin therapy, viral relapse was relatively frequent. Especially in elderly patients, the relapse rate was high after completing treatment, instead of low frequency of discontinuation by the adverse events.

Clinical features of adult patients with acute hepatitis B virus infection progressing to chronic infection.

Background. Information regarding the progression of acute hepatitis B virus (HBV) infection to chronic infection in adults is scarce. Methods. Twenty-five adult patients with acute HBV infection (14 men and 11 women, 18-84 years old), whose clinical features progressed to those of chronic infection (group A) or did not (group B), were studied retrospectively. Results. There were 3 and 22 patients in groups A and B, respectively. Two of the 3 patients of group A lacked the typical symptoms of acute hepatitis. No differences were found between groups with respect to age, sex, or HBV genotypes. However, total bilirubin and alanine aminotransaminase levels were significantly lower in group A. Conclusions. Three of the 25 adult patients with acute HBV infection progressed to chronic infection. Hepatitis was mild in these patients. Patients with mild acute hepatitis B or unapparent HBV infection may have a higher risk of progressing to chronic infection.

Clinical features and hepatitis B virus (HBV) genotypes in pregnant women chronically infected with HBV.

OBJECTIVE: The purpose of this study was to clarify the clinical features and hepatitis B virus (HBV) genotypes in pregnant women chronically infected with HBV. METHODS: Among 1,489 pregnant women who visited our hospital in 2010, 26 were positive for hepatitis B surface antigens (HBsAg). Of these subjects, 21 from whom informed consent was obtained were included in this study. The clinical features and HBV markers, including genotypes, were investigated. RESULTS: No adverse events were observed in the subjects or the neonates during pregnancy or the perinatal period. The HBV genotypes were C in 14 cases, D in six cases, and undetermined in one case. Hepatitis B e antigens and a high viral load (>7.0 log copies/mL) were found in four and six subjects with genotype C, respectively, and in none of subjects with genotype D. The alanine aminotransferase (ALT) levels and platelet counts were within the normal ranges during pregnancy in all subjects except two and three subjects with genotype C, respectively. Three subjects with genotype C showed transient elevations of ALT after delivery. CONCLUSION: The majority of subjects were anti-HBe-positive with normal ALT levels; however, some subjects with genotype C showed a high viral load, elevated ALT levels and/or low platelet counts. The pregnancies and deliveries were safe; however, transient elevations of ALT after delivery were observed in some subjects with genotype C.

Sustained virological response of patients with hepatitis C virus genotype 2 depends on pegylated interferon compliance.

AIM: Patients infected with hepatitis C virus (HCV) genotype 2 are more sensitive to interferon (IFN) therapy than those infected with genotype 1, but 10-20% of patients do not achieve a sustained viral response (SVR) to combination therapy with pegylated (PEG) IFN and ribavirin (RBV). This study examines the prognostic factors associated with SVR in patients infected with HCV genotype 2 treated with PEG IFN and RBV. METHODS: We treated 149 patients with chronic hepatitis C caused by HCV genotype 2. The patients received s.c. PEG IFN-α-2b (1.5 µg/kg) and a weekly weight-adjusted dose of RBV (600, 800 and 1000 mg per <60, 60-80 and >80 kg, respectively) for 24 weeks and then prognostic factors associated with the SVR were examined. RESULTS: Among the 149 patients, 138 completed the combination therapy and a sustained viral response was achieved in 71.8% of them. Univariate analysis showed that age, as well as mean RBV and PEG IFN doses were factors affecting the SVR (P = 0.012, =0.021, =0.014). Multivariate analysis identified age and mean PEG IFN dose (P = 0.021, =0.018, respectively) as factors involved in the SVR, but not mean RBV dose. CONCLUSION: The SVR of patients infected with HCV genotype 2 depended on the dosage of PEG IFN, but not of RBV. Selecting sufficient doses of PEG IFN for combination with RBV is critical for treating such patients.

Characteristics of small bowel tumors detected by double balloon endoscopy.

BACKGROUND: A few reports suggest that the emergence of double balloon endoscopy (DBE) has likely changed the clinical picture of small bowel tumors (SBTs). AIM: To further clarify the characteristics of SBTs detected by DBE. METHODS: A retrospective chart review was conducted in 227 patients who had undergone DBE. RESULTS: The SBT group contained more symptomatic patients than the non-SBT group (90% vs. 49%, P<0.0005) with a significantly higher rate of gastrointestinal symptoms at presentation (72% vs. 33%, P<0.005). Twenty patients (8.8%) were eventually diagnosed with SBT, and their indications for DBE were obscure gastrointestinal bleeding (n=5), abdominal pain (n=5), abdominal fullness (n=5), vomiting (n=2), and diarrhea (n=1). Tumors were located in the jejunum in 14 patients (70%) and in the ileum in 6 (30%). A final histological diagnosis was assigned to all 20 patients: primary adenocarcinoma (n=8, 40%), malignant lymphoma (n=5, 25%), metastatic cancer (n=4, 20%), gastrointestinal stromal tumor (n=1, 5%), carcinoid tumor (n=1, 5%) and inflammatory fibroid polyp (n=1, 5%). Stenosis or ulceration were the most frequently observed endoscopic findings (n=13, 65%). All primary adenocarcinomas and three of four (75%) metastatic cancers showed stenosis or ulceration. Three of five (60%) malignant lymphomas showed multiple lymphomatous polyps. All patients but one underwent surgical resection or chemotherapy or both. CONCLUSION: DBE is a safe and useful procedure that enables a precise diagnosis of SBTs.

Severe hypoglycemia associated with insulin-like growth factor II-producing liver metastasis from gastric carcinoma treated with overnight total parenteral nutrition via a central vein catheter reserve port.

Hypoglycemia caused by insulin-like growth factor II is difficult to control. A 77-year-old woman was diagnosed with gastric cancer and multiple liver metastases in September 2006 and underwent chemotherapy; however, at that time there were no symptoms of hypoglycemia. From January 2007 onwards, hypoglycemic comas and symptoms of hypoglycemia began to appear frequently. Her serum level of insulin was normal; thus, we suspected the presence of big insulin-like growth factor II was causing the hypoglycemia. This was proven by Western immunoblotting and we diagnosed non-islet cell tumor hypoglycemia associated with gastric cancer. Overnight nutrition provided via a central venous catheter port to prevent hypoglycemia allowed the patient to become ambulant and to remain free of hypoglycemic coma at follow-up until her death 7 months later.

Effects of long-term zinc treatment in Japanese patients with Wilson disease: efficacy, stability, and copper metabolism.

Wilson disease is an autosomal recessive disorder with copper metabolism. In Japan, the standard treatment is the administration of copper chelating agents, such as D-penicillamine and trientine. In this study, the authors used zinc acetate to treat Japanese patients with Wilson disease and investigated its efficacy. The 37 patients that comprise this study were found to have Wilson disease using clinical and biochemical tests and were administrated zinc acetate for 48 weeks. The authors followed the clinical symptoms and laboratory findings of the patients by assessing their complete blood counts, biochemical findings, as well as the results of urinalysis and special laboratory tests for copper and zinc metabolism. We also examined side effects of the treatment. Zinc acetate did not aggravate the hepatic or neurological symptoms of any of the patients. Blood biochemical analysis also did not reveal elevation of alanine aminotransferase, aspartate aminotransferase, and γ-glutamyltranspeptidase levels. Zinc treatment did not aggravate the patients' clinical signs and/or laboratory findings. However, it did improve some clinical symptoms of the Wilson disease patients. Although this agent had some side effects, none of them were severe. The authors measured spot urinary copper excretion, which gave an indication of the efficacy of treatment and of the sufficient dosage of zinc. We recommend maintaining a spot urinary copper excretion less than 0.075-µg/mg creatinine. The authors conclude that zinc acetate is an effective and safe treatment for Japanese patients with Wilson disease.

Modified technique for determining therapeutic response to radiofrequency ablation therapy for hepatocellular carcinoma using US-volume system.

In radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC), microbubbles appearing during the procedure make it difficult to determine effectiveness with ultrasonography (US) imaging. We developed a modified US-volume system and evaluated its efficacy for demonstrating response to therapeutic RFA. Our US-volume system displays multiplanar reconstruction (MPR) images providing a synchronized view with a US image along with past US-volume data in real-time side-by-side on a personal computer. Seventy-eight patients (94 nodules) were enrolled, of whom 35 (47 nodules) were evaluated using this system (US-volume group) and compared to the other 43 (47 nodules) examined before development of our system (control group). All nodules were clearly depicted by US. If the shortage of margin was predicted with US-volume system, we performed additional needle insertion. Tumor necrosis following RFA was graded by dynamic computed tomography as follows: Grade A, necrotic area surrounded in all directions with an adequate margin (>or=5 mm); Grade B, necrotic area surrounded in all directions, though some margin areas <5 mm; and Grade C, residual tumor or necrotic area smaller than the target tumor. In the US-volume group, the average tumor size was not smaller than that in the control (15.9+/-4.9 vs. 16.0+/-4.3 mm) and adequate margins were obtained (Grade A, B, C, 45/1/1 vs. 35/8/4; P<0.01). Further, there was a significant reduction in numbers of RFA sessions as compared to the control (1.03+/-0.17 vs. 1.12+/-0.32; P<0.01). In HCC patients undergoing RFA, our modified US-volume system accurately demonstrated therapeutic response, which led to a reduced number of RFA sessions.

Prospective study of chronic hepatitis C treated with reduced initial ribavirin dose.

BACKGROUND/AIMS: We prospectively examined the effects of a reduced initial dose of ribavirin (RBV) combined with pegylated interferon (Peg-IFN) to prevent RBV discontinuation due to adverse events in patients with chronic hepatitis C (CH-C) infection aged > 60y or with low hemoglobin values. METHODOLOGY: We enrolled 42 patients with hepatitis C virus (HCV) serotype 1. Twenty-one of them with hemoglobin values < 14g/dl or who were aged > 60y comprised group A. The other 21 patients (sex-and age-matched with group A) comprised group B, and received Peg-IFN (1.5 microg/ kg/week) and RBV (10-13 mg/kg/day) for 48 weeks. Group A initially received 200 mg less RBV than group B. RESULTS: Higher hemoglobin values persisted at 16, 20, 24 and 44 weeks, and the sustained viral response (SVR) ratio was lower in group A than in group B (17% vs. 57%). RBV therapy was discontinued due to severe anemia in group B, but not in group A. CONCLUSIONS: The reduced initial dose of ribavirin prevented discontinuation due to anemia. However, this protocol cannot be recommended even for patients with CH-C accompanied by low hemoglobin or advanced age, since a sufficient SVR ratio is not achievable.

Radiofrequency ablation therapy for hepatocellular carcinoma in elderly patients.

BACKGROUND AND AIM: With the aging of society, the number of elderly patients with hepatocellular carcinoma (HCC) has been increasing in Japan. The Government of Japan defines elderly as being over 65 and has divided the elderly into two stages: the first elderly stage (< 75 years old) and the second elderly stage (> or = 75). We investigated the efficacy and safety of radiofrequency ablation therapy (RFA) in patients in the second elderly stage in comparison with other HCC patients, retrospectively. METHODS: Two hundred six patients with HCC, who were within the Milan criteria, with low-grade performance status (0 or 1) and a Child-Pugh classification of A or B were enrolled. All were treated with RFA from January 2000 to December 2008 as an initial therapy and were divided into elderly HCC group (e-HCC group; > or = 75, n = 63) and non e-HCC group (< 75, n = 143), and their clinical data and survival rates were compared. RESULTS: Age and the level of protein induced by vitamin K absence or antagonist (PIVKA-II) were higher in the e-HCC group as compared with the non e-HCC group (78.3 +/- 3.2 vs 64.2 +/- 7.5 years, 676.3 +/- 2643.7 vs 142.4 +/- 442.2 mAU/mL: P < 0.01, respectively). There were no significant differences for Child-Pugh class, tumor node metastasis stage, and Japan Integrated Stage score and in survival rates after 3, and 5 years between the groups (e-HCC group: 82.5% and 49.7%, respectively; non e-HCC group: 78.3% and 57.5%, respectively). There were no severe complications in the e-HCC group. CONCLUSIONS: Elderly HCC patients, who have good performance status, should be treated in the same manner and with the same strategy as young HCC patients.

Risk factors for death in 224 cases of hepatocellular carcinoma after transcatheter arterial chemoembolization.

BACKGROUND/AIMS: Transcatheter arterial chemoembolization (TACE) has been reported as effective therapy for unresectable hepatocellular carcinoma (HCC), however, few have described methods for predicting prognosis, especially in patients treated by repeated TACE. To determine risk factors for death and try to predict the prognosis, we evaluated clinical data. METHODOLOGY: We retrospectively analyzed the clinical parameters of 224 patients with unresectable HCC treated with repeated TACE from January 1997 to December 2007. TACE was repeated when recurrence was diagnosed by tumor marker elevation and/or dynamic computed tomography findings. Factors affecting survival were evaluated using multivariate analysis after univariate analysis. Next, we combined the score for each significant factor into a single prognostic score and added up the positive factors in each case, then analyzed the significance of prognosis, after which the results were compared with other prognostic scoring systems. RESULTS: Multivariate analysis revealed that bilobular HCC, alpha-fetoprotein (> or = 400 ng/ml), tumor invasion of the portal vein, tumor size (> or = 10 cm), and albumin (< 2.8 g/dl) were related to poor prognosis, and developed a prognostic scoring system from those. According to that score, patients were classified into 5 groups. CONCLUSION: Our scoring system was easily performed and the results showed that repeated TACE should not be administered to patients with scores of 3 or more.

Diabetes pattern on the 75 g oral glucose tolerance test is a risk factor for hepatocellular carcinoma in patients with hepatitis C virus.

BACKGROUND: Patients with hepatitis C virus (HCV) frequently show glucose intolerance. Diabetes mellitus (DM) has been proposed to be a risk factor for hepatocellular carcinoma (HCC). AIMS: The aim of this study is to clarify the influence of glucose intolerance as evaluated by the 75 g oral glucose tolerance test (OGTT) on hepatocarcinogenesis in patients with HCV. METHODS: This study was carried out in a cohort of 197 patients with HCV who had not been previously diagnosed as having DM. All patients underwent the 75 g OGTT at entry. They were also screened for HCC and, thereafter, the rate of hepatocarcinogenesis was compared between the patients with and without glucose intolerance. RESULTS: Based on the results of the 75 g OGTT, 125 (63%) had normal glucose tolerance (NGT), 49 (25%) had impaired glucose tolerance (IGT) and 23 (12%) had the DM pattern. HCC occurred more frequently in patients with the DM pattern than in patients with either NGT or IGT. Even in patients without advanced liver fibrosis, HCC was more frequently observed in patients with DM than in patients with NGT. A multiple logistic regression analysis showed advanced liver fibrosis, the DM pattern on the 75 g OGTT, an older age and gamma-glutamyltransferase to all be independent risk factors related to hepatocarcinogenesis. CONCLUSIONS: A DM pattern on the 75 g OGTT was thus found to be associated with hepatocarcinogenesis and the 75 g OGTT is considered to be useful for identifying this risk factor for HCC in patients with HCV.

Primitive neuroectodermal tumor of the pancreas.

The primitive neuroectodermal tumor (PNET) of the pancreas, a member of Ewing's sarcoma family of tumors, is extremely rare. We treated a 37-year-old Japanese man who had a solitary pancreatic tumor 40 mm in diameter and multiple hepatic tumors with surgical resection. The PNET was positive for CD99 on immunohistochemical staining. Fluorescence in situ hybridization (FISH) was also performed, which revealed a Ewing sarcoma breakpoint region 1 (EWSR1) 22q12 rearrangement. According to the Japan-Ewing protocol, chemotherapy with Ifomide (ifosfamide), etoposide, vincristine, and cyclophosphamide was given after surgery. To the best of our knowledge, to date 13 PNET cases have been reported with a mean age for all patients of 19.3 years old. Surgical resection was performed in most cases and some patients received postoperative chemotherapy. The clinicopathologic characteristics and management of this extremely rare disease are also discussed.