Usefulness of chemoradiotherapy for inoperable gastric cancer.

Introduction Radiotherapy is not commonly used for the treatment of gastric cancer in Japan, where surgery is the standard local treatment. We report the results of chemoradiotherapy in patients with advanced or recurrent gastric cancer which was deemed difficult to treat surgically. Methods Twenty-one patients with gastric cancer (including sixteen with advanced/recurrent gastric cancer and five with poor general condition) underwent chemo-radiotherapy, for whom the therapeutic efficacy, toxicity and survival period were analysed. Results The tumour response to chemoradiotherapy was categorised as complete, partial, stable or progressive in 5, 9, 3, and 4 patients, respectively, with an overall response rate of 67%. No serious complications such as gastrointestinal perforation or bleeding occurred, and no cardiac, hepatic or renal dysfunction developed during the follow-up period. The mean survival time was 19.8 months (range, 3-51 months). One patient died of another disease, 18 died of primary cancer and the cause of death was unknown in 2 patients. Conclusions Chemoradiotherapy appears to be an effective treatment for localised gastric cancer without distant metastases, but further studies are needed to determine the indications for chemoradiotherapy and late adverse effects, as well as the chemotherapy regimens to be used.

Clinical and endoscopic characterization of depressed gastric adenoma.

BACKGROUND AND STUDY AIM: Depressed gastric adenoma remains poorly characterized because it is rare, and is infrequently detected by endoscopy. The aim of this study was to elucidate clinical and endoscopic characteristics of depressed adenoma of the stomach. PATIENTS AND METHODS: 95 consecutive patients who underwent endoscopic resection of gastric adenomas were studied. Gastric adenomas, diagnosed according to the Vienna classification, were endoscopically classified into two types: depressed and protruding adenomas. In order to clarify endoscopic features of gastric adenomas, we performed indigo carmine chromoendoscopy as well as magnifying endoscopy with narrow band imaging, which yields clear images of mucosal microvasculature. RESULTS: 12% of 100 gastric adenomas resected from 95 patients were depressed adenomas. Age and gender were comparable between patients with each type. Depressed adenomas (15.9 +/- 6.2 mm) were significantly larger in diameter than protruding adenomas (10.6 +/- 8.0 mm) (P = 0.01). Half of depressed adenomas were reddish in color, whereas only 18% of protruding adenomas were reddish. Magnifying endoscopy with narrow band imaging showed that 71% of depressed adenomas had a regular ultrafine network pattern of mucosal microvasculature, which was not seen in protruding adenomas. Intramucosal carcinomas were more frequently found in depressed adenomas (25%) than in protruding adenomas (4.5%). CONCLUSIONS: In comparison with protruding adenomas, depressed adenomas were rare and appeared endoscopically as large and reddish with a specific regular ultrafine network pattern of mucosal microvasculature. Depressed adenomas should be endoscopically resected because intramucosal carcinomas were found in a quarter of them.

Magnifying endoscopy combined with narrow band imaging system for early gastric cancer: correlation of vascular pattern with histopathology (including video).

BACKGROUND AND STUDY AIMS: The narrow band imaging (NBI) system consists of a sequential electronic endoscope system and a source of light equipped with new narrow band filters, yielding very clear images of microvessels on mucosal surfaces. The aim of this prospective study was to measure the correlation between the magnified images obtained with the NBI system and the histological findings, especially with regard to the vascular pattern. In addition, three-dimensional images of microvessels were reconstructed using a laser scanning microscope. PATIENTS AND METHODS: Between July 2001 and August 2003, 165 patients with depressed-type early gastric cancer lesions were enrolled in the study. The lesions were carefully observed with magnification using the NBI system. The images, the pathological characteristics of the lesions, and three-dimensionally reconstructed images of the microvascular networks in biopsied specimens were carefully analyzed. The microvascular patterns were classified into three groups: A, fine network; B, corkscrew; and C, unclassified pattern. The endoscopic images were compared with the histological findings. RESULTS: Of the three types of filter available for use with the NBI system, microvascular formation was best enhanced in B mode images produced using short wavelengths, which focus on the superficial mucosal layer. Among 109 cases of differentiated adenocarcinoma, the group A microvascular pattern was observed in 72 cases (66.1 %). Among 56 cases of undifferentiated adenocarcinoma, the group B pattern was observed in 48 cases (85.7 %; P = 0.0011) The microvascular structure observed using the NBI system corresponded with the superficial mucosal layer in the three-dimensional images obtained using laser scanning microscopy and the resected specimens. CONCLUSIONS: Magnifying endoscopy performed in combination with the NBI system is not sufficient to replace conventional histology, but is capable of predicting the histological characteristics of gastric cancer lesions.

Alanine aminotransferase elevation not associated with fatty liver is frequently seen in obese Japanese women.

OBJECTIVE: To determine the prevalence of fatty liver and alanine aminotransferase (ALT) elevation in obese Japanese women and to clarify the factors contributing to fatty change and ALT elevation in the cohort. DESIGN: Cross-sectional and population-based study. SUBJECTS: From 4366 women who received their annual health check-up, 4211 women were selected for analysis. All 4211 women were negative for hepatitis virus markers. MEASUREMENTS: Peripheral blood cell counts, liver biochemical tests, fasting glucose, cholesterol and triglyceride levels, uric acids, glycosylate hemoglobin A1c, and ultrasound examination. RESULTS: Ultrasonographic evidence of fatty liver and ALT elevation was seen in 391 (9.3%) and 238 (5.7%), respectively, of the 4211 women. Frequencies of both fatty liver and ALT elevation increased with increase in the degree of obesity. The frequency of ALT elevation was higher in women with fatty liver than in women without fatty liver among the nonobese or mildly obese group. However, the frequency of ALT elevation was not significantly different between women with fatty liver and women without fatty liver among the severely obese group. Multivariate analysis showed that obesity, hemoglobin (> or = 14 g/dl), triglyceride (> or = 150 mg/dl), diabetes mellitus, and fatty liver were significant predictors of ALT elevation. However, only two variables, hemoglobin (> or = 14 g/dl) and presence of diabetes, were significant in the severely obese group. CONCLUSIONS: ALT elevation not associated with fatty liver was frequently seen in obese women, suggesting that obesity is directly associated with the elevated ALT level in Japanese obese women. In addition, hemoglobin (> or = 14 g/dl) was a strong predictor of ALT elevation in the severely obese group.

Hepatitis B virus concentrations in serum determined by sensitive quantitative assays in patients with established chronic hepatitis delta virus infection.

To clarify the correlation between hepatitis B virus (HBV) DNA levels and serum alanine aminotransferase (ALT) levels in patients with established chronic hepatitis delta virus (HDV) infection, sensitive HBV quantitative assays were used for the study. Thirty-four consecutive patients with chronic liver disease who were positive for both hepatitis B surface antigen (HBsAg) and antibody to HDV (anti-HDV), including 19 patients with chronic hepatitis, 8 patients with liver cirrhosis and 7 patients with hepatocellular carcinoma. All were negative for hepatitis Be antigen (HBeAg) and positive for antibody to HBeAg. HBV DNA was detected in 25 (73.5%) of the 34 patients using real-time detection PCR, and the HBV DNA levels of these patients were significantly lower compared with HBeAg status and ALT level-matched patients with chronic liver disease positive for HBsAg but negative for anti-HDV. There was no correlation between serum HBV DNA and ALT levels among the 34 patients with chronic liver disease positive for anti-HDV. Whereas serum ALT levels in anti-HDV-positive HBsAg carriers with HDV RNA were significantly higher than those without HDV RNA. Liver damage in patients with established chronic HDV infection may be caused mainly by ongoing HDV infection not by HBV replication.

Correlation between serum transaminase activity and virus load among patients with chronic liver disease type B.

Newly developed hepatitis B virus (HBV)-DNA quantitative assays, transcription-mediated amplification and hybridization protection assay (TMA-HPA) and branched-DNA assay were clinically evaluated. The subjects consisted of 160 chronic HBV carriers; 48 were hepatitis Be antigen (HBeAg)-positive, whereas 109 were anti-HBe-positive (three were both negative). All subjects with HBeAg, except one, showed high HBV-DNA replication levels (>/=10(5.8) copies/ml). In HBeAg negative subjects, there was a strong correlation between the serum HBV-DNA and alanine aminotransferase (ALT) levels; ALT level was usually normal if the samples tested showed an HBV-DNA level less than 10(5)/ml, whereas, the majority of the sera with an HBV-DNA concentration greater than 10(7)copies/ml showed elevation in serum ALT level. An intermediate range of HBV-DNA level (10(5)-10(7) copies/ml) was associated with variable ALT activity. In conclusion, a serum HBV-DNA level associated with ALT elevation was lower in patients with type B chronic liver disease negative for HBeAg compared with their HBeAg-positive counterparts. There was usually no or mild liver disease activity when patients with chronic HBV infection have serum HBV-DNA levels less than 10(5)copies/ml.

Up-regulation of carnitine transporters helps maintain tissue carnitine levels in carnitine deficiency induced by pivalic acid.

PURPOSE: Pivalic acid (PVA) forms conjugates with endogenous carnitine and enhances its excretion. The purpose of this study is to determine whether tissue carnitine levels decrease in parallel with plasma levels in carnitine deficiency induced by PVA. METHODS: PVA was orally administered to rats for 5 days. Carnitine levels in plasma, liver, kidney, muscle, and heart were monitored. The tissue uptake clearance (CLuptake) was determined in vivo by the integration plot method. Hepatocytes were prepared from control and PVA-treated rats, and the uptake of L-carnitine was determined. RESULTS: Plasma concentrations of L-carnitine decreased as a result of the enhanced carnitine elimination as pivaloylcarnitine (PCN) when rats were treated with PVA. However, L-carnitine concentrations in liver, muscle, and heart remained relatively constant during the study. period. CLuptake increased in liver and muscle and, thus, the rate of carnitine uptake from plasma into these tissues did not change even at low plasma concentrations. This helps maintain carnitine levels in these tissues. Up-regulation of carnitine transporters is suggested to be a mechanism for the increased CLuptake. CONCLUSIONS: In the carnitine deficiency state induced by PVA, increased CLuptake owing to up-regulation of carnitine transporters is suggested to help maintain carnitine levels in some tissues.

[The effects of percutaneous endoscopic gastrostomy feeding in patients with swallowing disturbance].

BACKGROUND AND PURPOSE: Because the number of patients who need home healthcare has recently increased in Japan, Percutaneous endoscopic gastrostomy (PEG) will soon become more popular. This study aims to examine the effects of enteral alimentation via PEG. MATERIAL AND METHODS: The subjects were 18 patients who underwent PEG instead of receiving total parental nutrition (TPN) (TPN-to-PEG group), 13 patients who underwent PEG instead of receiving enteral nutrition through a naso gastric tube (NG-to-PEG group), and 11 healthy volunteers (control). Morphological changes of the small bowel mucosa and activities of daily life (ADL) after PEG were also investigated. RESULTS: In the TPN-to-PEG group, the serum level of total protein and albumin, length of duodenal villi, ration of positive proliferative cells, width of duodenal microvilli and ADL markedly increased. In the NG-to-PEG group, body weight and ADL were markedly improved after PEG. CONCLUSION: Nutrition via PEG is superior to TPN or enteral nutrition with an NG tube. I conclude that PEG will become the first choice for improving nutrition in patients with dysphasia and will contribute to continuous enteral nutrition for home care.

A patient with primary biliary cirrhosis associated with autoimmune hemolytic anemia.

Primary biliary cirrhosis is often associated with autoimmune conditions, such as thyroid disease, sicca complex, and rheumatoid arthritis. However, an association with autoimmune hemolytic anemia has rarely been reported. We present a case of primary biliary cirrhosis associated with warm type autoimmune hemolytic anemia, and we review prior reports.

Hepatitis delta virus genotype IIb predominates in an endemic area, Okinawa, Japan.

Hepatitis delta virus (HDV) infection is relatively common in the Miyako Islands, Okinawa, Japan, where the infection has been reported to be associated with low pathogenicity. HDV RNA extracted from each of 6 patients with HDV-related chronic liver disease living in the islands was amplified by reverse transcription-polymerase chain reaction and examined genetically to determine the HDV genotype. All isolates from the 6 patients were classified as genotype II by the neighbor-joining method. However, these isolates had relatively low homology (75-81%) to the HDV genotype II isolate reported from Japan, and showed relatively high identity (83-95%) to the novel genotype II isolate (HDV genotype IIb) recently reported from Taiwan. Phylogenetic analysis showed that the 6 isolates form a novel group within HDV genotype II. Furthermore, there was notable variation in sequence among the 6 isolates compared with the relatively close clustering of HDV isolates within limited areas (e.g., United States, Archangelos, Turkey, Albania, Peru). HDV genotype II in the Miyako Islands is therefore unique, and HDV infection may have been introduced at a relatively early time in this area.

Prevalence and clinical features of hepatitis delta virus infection in the Miyako Islands, Okinawa, Japan.

The aims of this study were twofold: (1) to determine the prevalence and clinical features of hepatitis delta virus (HDV) infection among subjects positive for hepatitis B surface antigen (HBsAg) living in the Miyako Islands, Okinawa Prefecture, Japan, and (2) to clarify the relationship between HDV-RNA level and severity of HDV-related liver disease. One hundred and ninety-nine HBsAg-positive subjects (123 asymptomatic carriers [ASCs], 3 patients with acute hepatitis [AH], 50 patients with chronic hepatitis [CH], 15 patients with liver cirrhosis [LC], and 8 patients with hepatocellular carcinoma [HCC], were tested for antibody to HDV (anti-HDV) by radioimmunoassay. Anti-HDV-positive individuals were examined to determine semi-quantified HDV-RNA level by polymerase chain reaction (PCR). The overall prevalence of anti-HDV among the 199 subjects was 21.1%. The positivity rate tended to increase with age or the severity of the underlying liver disease: anti-HDV-positive rates were 10.6% (13/123) in ASCs, 32.0% (16/50) in patients with CH, 40.0% (6/15) in patients with LC, and 87.5% (7/8) in patients with HCC. None of the patients with AH were positive for anti-HDV. There was no correlation between semi-quantified serum HDV-RNA levels and the severity of chronic liver disease in patients positive for anti-HDV. The present study showed the local spread of HDV infection in the Miyako Islands, Okinawa, Japan. Although the anti-HDV positivity rate tended to increase with the severity of the underlying liver disease, the severity of HDV-related liver disease did not correlate with the semi-quantified serum HDV-RNA level.

Relation between reactivity to the NS-4 region peptides of hepatitis C virus (HCV) and clinical features among patients infected with HCV genotype 1b.

Nearly all patients infected with hepatitis C virus (HCV) genotype 1b have reactivity to the core (c22-3) or non-structural (NS)-3 region (c33c) protein in a second-generation recombinant immunoblot assay (RIBA-2). However, reactivities to the NS-4 region antigens (5-1-1, c100-3) vary among patients. To clarify whether differences in serological reactivities to the NS-4 antigens are associated with the clinical features or response to interferon (IFN) therapy of patients infected with hepatitis C virus (HCV) genotype 1b, we clinically investigated 115 such patients. Positive reactions to 5-1-1 and c100-3 were seen in 75.7 and 79.1%, respectively, of the patients. There were no differences between the patients with and those without antibodies to NS-4 region antigens (5-1-1, c100-3) with regard to age, duration of HCV infection, severity of liver disease and virus load. Fifty-one of the patients were treated with recombinant IFN-alpha, and 17 of the 51 patients showed sustained response to the therapy. The sustained response was more frequently seen in the patients positive for antibodies to both 5-1-1 and c100-3 as compared with those negative for either or both antibodies (41.0% vs. 8.3%, P<0.05).

Determination of hepatitis delta virus (HDV)-RNA in asymptomatic cases of HDV infection.

OBJECTIVES: To assess the frequency of hepatitis delta virus (HDV) viremia in asymptomatic cases of HDV infection and the clinical significance of the HDV viremia, we conducted a cross-sectional, community-based study. METHODS: Of 2207 examinees, 210 (9.5%) were found to be positive for hepatitis B surface antigen (HBsAg). Antibody to HDV was detected in 47 (22.4%) of the 210 examinees, and 43 of the 47 were further evaluated for serum HDV-RNA by polymerase chain reaction. RESULTS: Twenty-one (48.8%) of the 43 had detectable levels of HDV-RNA in serum, and 22 (51.2%) were negative for serum HDV-RNA. The majority (61.9%) of the HDV-RNA-positive HBsAg carriers had high levels of serum ALT. In contrast, the frequency of an abnormally high level of serum ALT was only 9.1% in the HBsAg carriers positive for HDV antibody but negative for HDV-RNA, and the frequency did not differ from that seen in the HBsAg-negative individuals. The semiquantified HDV-RNA levels did not correlate with the serum ALT levels. CONCLUSION: Seropositivity of HDV-RNA was strongly associated with liver cell damage, even in asymptomatic cases. The absence of a detectable level of serum HDV-RNA might be related to previous HDV infection.

Seroepidemiological study on hepatitis delta virus infection in the Irabu Islands, Okinawa, Japan.

A seroepidemiological study was performed to clarify the prevalence of hepatitis delta virus (HDV) infection among the general population in the Irabu islands, Okinawa, Japan. Of 2028 healthy people examined who had received their annual health check-up in 1994-95, 195 (9.6%) were positive for hepatitis B surface antigen (HBsAg). Of these 195 HBsAg-positive individuals, 46 (23.6%) showed a positive reaction for antibody to HDV (anti-HDV). The positivity rate of anti-HDV among HBsAg-positive subjects tended to increase with age up to 50-59 years of age. The prevalence of anti-HDV also varied among the seven districts in the islands (0-63.3%). None of the anti-HDV-positive subjects was included in the high risk group for parenterally transmitted diseases. The unusually high prevalence of anti-HDV among HBsAg-positive individuals, particularly in the older age groups, seemed to reflect the natural prevalence or previous HDV infection, rather than a current or imported infection of HDV. Although the great majority of HBsAg-positive subjects with anti-HDV were asymptomatic, abnormally high values of serum transaminases were more frequently seen in these subjects compared with HBsAg-positive subjects without anti-HDV.

High proportion of false positive reactions among donors with anti-HCV antibodies in a low prevalence area.

Among 39,656 voluntary blood donors in Okinawa Prefecture, Japan, 115 (0.29%) were repeatedly reactive for antibody to hepatitis C virus (anti-HCV) by second generation (2nd-gen) passive hemagglutination assay (PHA). Positive serum samples were tested for anti-HCV using three different enzyme immunosorbent assays (ELISAs; Abbott 2nd EIA, UBI-HCV-EIA, JCC-2) and for HCV-RNA by the polymerase chain reaction (PCR). The 115 2nd-gen PHA-positive sera were divided into three groups according to the agglutination titers; > 2(10) (high titer group), 2(7)-2(9) (median), 2(5)-2(6) (low). All but one serum (44/45) in the high PHA titer group reacted in each of the three second screening ELISAs. Furthermore, 43 (97.7%) of the 44 sera contained HCV-RNA by PCR. In the median titer group, 11 of the 13 samples tested were positive by each of the three ELISAs, and 4 (36.4%) of the 11 showed reaction by PCR. On the other hand, all of the 38 sera tested in the low titer group were negative for HCV-RNA by PCR, and 24 of the 38 were also negative by each of the three ELISAs. Most of the low titer positive reactions in the 2nd-gen agglutination assay seemed to be false positive. In Okinawa Prefecture, the prevalence of anti-HCV among blood donors is much lower than in the rest of Japan (0.29% vs. 1.11%). Moreover, a significant proportion of these sera were low titer by the PHA assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Seroepidemiological study of hepatitis delta virus infection in Okinawa, Japan.

A seroepidemiological study on hepatitis delta virus (HDV) infection was conducted in the Okinawan islands, the area of Japan where hepatitis B virus infection is most prevalent. The subjects of this study included 116 asymptomatic hepatitis B surface antigen (HBsAg) carriers, 48 patients with chronic hepatitis (CH), 19 with liver cirrhosis (LC), and 11 with hepatocellular carcinoma (HCC). Among the 194 serum samples examined, a total of 10 (5.2%) were anti-HDV seropositive. Anti-HDV was detected in 2 (1.7%) of the 116 asymptomatic HBsAg carriers, in 3 (6.3%) of the 48 patients with CH, and in 5 (26.3%) of the 19 with LC. However, none of the patients with HCC had detectable anti-HDV. Eight of the 10 were born in the Miyako island group and the remaining 2 on the main island of Okinawa. Since the subjects included 34 individuals who were living and/or born in the Miyako islands, the positive rate of anti-HDV in the islands was 23.5%. This study demonstrates the existence of an endemic area of HDV infection in Japan.

[Clinical study of eradicated and resistant patients to treatment with ivermectin for strongyloidiasis].

We treated 70 patients with strongyloidiasis (41 males and 29 females) with ivermectin (IVM), and obtained the following results: 1. The eradication rates at 1-2 months, 3-4 months and 5-6 months after treatment were 90.7% (49 of 54 patients), 100.0% (47 of 47 patients) and 95.7% (45 of 47 patients), responsively. Twelve patients were resistant (non-responsive) to treatment. 2. When compared to patients whose parasites were completely eradicated, the resistant patients showed the following results: 1) Incidence of symptoms observed before treatment was significantly lower (50.0% vs. 84.5%). 2) Positive rate of anti-HTLV-I antibody was significantly higher (66.7% vs. 20.7%). 3) Blood eosinophil counts before treatment were significantly lower (266.6 +/- 117.2/mm3 vs. 533.2 +/- 429.7/mm3). 4) Serum IgE levels before treatment were significantly lower (217.2 +/- 442.9 IU/ml vs. 1,076.8 +/- 2,108.0 IU/ml). 5) There were no significant differences in age, sex and dosage of ivermectin. 3. Comparing anti-HTLV-I antibody positive and negative patients, the following results were obtained: 1) Eradicated patients; a) Eosinophils and IgE levels before and after the first administration of medicine in anti-HTLV-I antibody positive patients were significantly lower than those of negative patients. b) Gammaglobulin levels before treatment and after both administrations of the drug, IgG before therapy and OKT4/OKT8 after therapy were significantly higher than in anti-HTLV-I antibody positive patients. 2) Resistant patients; Eosinophils after treatment were significantly lower in anti-HTLV-I antibody negative patients than in positive patients.(ABSTRACT TRUNCATED AT 250 WORDS)