Meloxicam as an adjuvant to peginterferon-α-2a and ribavirin treatment for genotype 1 chronic hepatitis C: A randomized trial.

AIM: In this multicenter, randomized trial, we evaluated the effectiveness of meloxicam - a non-steroidal anti-inflammatory drug - as an adjuvant for enhancing antiviral efficacy and preventing neutropenia during the treatment of patients with genotype 1 chronic hepatitis C using peginterferon and ribavirin. METHODS: A total of 60 patients were randomly assigned, in a 1:1 ratio, to either the meloxicam or the control group after stratification by neutrophil count. Both groups received weekly peginterferon-α-2a (180 µg) and a weight-based dose of ribavirin for 48 weeks. The meloxicam group received meloxicam (10 mg/day) for the first 8 weeks after initiation of treatment. RESULTS: Through intent-to-treat analysis, we found that the sustained virological response rate in the meloxicam group (19/30, 63.3%) was significantly higher than in the control group (11/30, 36.7%, P < 0.05). The relapse rate was more than twice as high (45%) in the control group than in the meloxicam group (19.0%); however, this difference was not statistically significant. The rate of neutrophil decrease, calculated by dividing the lowest value observed during the first 8 weeks by pretreatment count, was significantly smaller in the meloxicam group (55.1 ± 14.3%) than in the control group (62.3 ± 9.6%, P < 0.05). CONCLUSION: Meloxicam enhanced antiviral efficacy and reduced the decline in neutrophil counts for the peginterferon and ribavirin treatment of genotype 1 chronic hepatitis C. This drug could be a reasonable adjuvant for the treatment of patients with chronic hepatitis C. The present study including a small number of patients warrants larger clinical trials.

A case of small bowel ulcer caused by NSAIDs and detected after capsule endoscope retention.

We recently detected an annular ulcer thought to have been caused by non-steroidal anti-inflammatory drugs (NSAIDs) when we performed small bowel capsule endoscopy on a patient with suspected small-bowel bleeding and a history of frequent use of oral NSAIDs. The patient was a 64-year-old woman who complained of bloody stools and abdominal pain. The annular ulcer showed concentric stenosis, which caused retention of the capsule endoscope. NSAIDs are some of the most frequently used anti-inflammatory analgesics, and even more frequent use can be expected with the aging of society. No reports to date appear to have described retention of a capsule endoscope due to annular ulceration caused by NSAIDs. We report herein our experience with a patient showing small-bowel ulcer caused by NSAIDs.

Weight-based high- and low-dose ribavirin in combination with peginterferon α-2b therapy for genotype 2 chronic hepatitis C: A randomized trial.

AIM: The optimal ribavirin dose in the treatment of patients infected with hepatitis C virus (HCV) genotype 2 remains to be elucidated. We aimed to seek the optimal ribavirin dose required for this genotype in a randomized trial. METHODS: We compared the efficacy and tolerability of the 24-week peginterferon α-2b (1.5 µg/kg/week) therapy in combination with a weight-based higher dose (600-1000 mg) and lower dose (400-800 mg) of ribavirin for genotype 2 patients. Noninferior margin was set at 10%. RESULTS: A total of 120 patients were randomized to a higher-dose or a lower-dose group. Sustained virological response (SVR) by intention-to-treat analysis was achieved in 47/58 (81.0%, 90% confidential interval [CI]: 72.6-89.5) patients in the higher-dose group and 41/60 (68.3%, 90% CI: 58.5-78.2) patients in the lower-dose group (difference, -12.7%; 90% CI, -25.7 to 0.3). Relapse rates were 10% and 21.6% in the higher-dose and the lower-dose groups, respectively. Multiple logistic regression analysis showed that ribavirin dose/kg body weight was the only significant predictor of SVR (≥9.5 mg/kg per day vs <9.5 mg/kg per day; odds ratio = 3.34; 95% CI, 1.41-7.92; P = 0.006). Twenty-one (36.2%) in the higher-dose group required ribavirin dose reduction because of anemia, whereas seven patients (11.7%) did in the lower-dose group (P < 0.01). Three of the higher-dose group and two of the lower-dose group required premature termination of therapy. CONCLUSIONS: Weight-based lower-dose ribavirin regimen was not equivalent to the higher-dose counterpart in the treatment of HCV genotype 2. We discourage treating these patients with low-dose ribavirin regimens. The peginterferon therapy in combination with ribavirin at a weight-based higher dose (600-1000 mg) remains the standard-of-care treatment for this genotype.

Good response chemotherapy for late-recurring gastric cancer in the gluteals, with peritoneal and retroperitoneal dissemination.

A 64-year-old woman presented with advanced gastric cancer (signet ring cell carcinoma) and underwent total gastrectomy in 1996. Postoperative recovery was good, and she was monitored regularly on an outpatient basis. Abdominal computed tomography in 1999 revealed a soft tissue shadow ventral to the origin of the celiac artery. Careful monitoring was continued on an outpatient basis. The patient began to experience gluteal swelling and pain in April 2008. Symptoms rapidly exacerbated and the patient was hospitalized for further examination. Gluteal muscle biopsy revealed signet ring cell carcinoma and bilateral hydronephrosis. Gluteal recurrence of the original gastric cancer was suggested, and systemic chemotherapy consisting of S-1 at 100 mg/day (3 weeks on, 1 week off) and CDDP (day 8) was started. Following the 6th cycle of chemotherapy, gluteal symptoms disappeared and the patient was judged to have achieved clinical complete response (CR). No adverse events or image findings suggesting new recurrence have since been identified. The patient received a total CDDP dose of 585 mg and clinical CR has been maintained as of 14 years after total gastrectomy and 18 months after recurrence.

Differential impact of adherence to pegylated interferon and ribavirin in the treatment of genotype 1 high viral titer chronic hepatitis C.

To clarify the impact of adherence, we treated 122 genotype 1 high viral titer chronic hepatitis C patients with pegylated interferon (peg-IFN) and ribavirin for 48 weeks at nine referral hospitals, and evaluated the prognostic factors with a focus on the adherence to the treatment. This study included 68 (55.7%) treatment-naïve patients and 54 (44.3%) patients who did not respond to the previous treatment. Multivariate analysis revealed adherence to peg-IFN and ribavirin as the only significant predictor. Sustained virological response (SVR) rate was 72.2%, 19.0%, and 27.3% in patients given ≥80%, 60%-80%, and <60% dose peg-IFN, respectively, and was 68.6%, 41.2%, and 5.3% in those given ≥80%, 60%-80%, and <60% dose ribavirin, respectively. SVR rate sharply fell when exposure to peg-IFN was below 80% whereas it decreased in a stepwise manner as for ribavirin. Therefore, ≥80% of peg-IFN and as much as possible dose of ribavirin are desired to achieve SVR in the treatment of genotype 1 high viral titer chronic hepatitis C.

[Is whole body bone mineral density measured by the dual energy X-ray absorptiometry applied to evaluate risk of osteoporosis among Japanese adult females?].

To measure whole body fat accurately, the dual energy X-ray absorptiometry (DXA) is widely utilized. Simultaneously, bone mineral density (BMD) of the whole body can also be measured. BMD is one of important information to diagnose osteoporosis. However, it is not established to use whole body BMD for this diagnosis. It is recommended that lumbar and/or hip BMD should be used for diagnosing osteoporosis by the guideline for prevention and treatment of osteoporosis. Although it is possible to measure whole body BMD and lumbar and/or hip BMD separately at the same visit, it is inevitable to expose patients to more X-ray. Therefore, an aim of this study is to elucidate the relationship between whole body BMD and lumbar BMD to find the cut off point of whole body BMD for screening of osteoporosis. Two hundred and thirty six Japanese adult females were ascertained to this study. Whole body BMD and lumbar BMD of each subject were measured with the use of Delphi W (Hologic, USA). One hundred and sixty five subjects were judged as possible osteoporosis (less than 80% of young adult mean (YAM) of lumbar BMD and/or definite fracture of lumbar vertebras). The cut off point of whole body BMD for screening possible osteoporosis was estimated by receiver operated characteristic (ROS) analysis. The cut off point of whole body BMD was 84% of YAM, equivalent to 80% of YAM of lumbar BMD, with the following sensitivity and specificity (0.84 and 0.79, respectively), indicating that whole body BMD could be used for screening osteoporosis.

Transcatheter arterial chemoembolization plus radiofrequency ablation therapy for early stage hepatocellular carcinoma: comparison with surgical resection.

BACKGROUND: Radiofrequency ablation (RFA) is becoming a well-known local therapy for hepatocellular carcinoma (HCC). Transcatheter arterial chemoembolization (TACE) is expected to enhance the effects of subsequent RFA by reducing arterial blood flow. However, the long-term efficacy of this combined therapy has not been elucidated. In this study, the survival rates of patients who received TACE combined with RFA (TACE + RFA) were compared with those of patients treated surgically. METHODS: The study included consecutive patients who received TACE+RFA or surgical resection as the initial curative treatment for HCC between 2000 and 2005 at Tokai University Hospital. Inclusion criteria were a single HCC

Eight-week oral administration of meloxicam, a non-steroidal anti-inflammatory drug, prevents dose reduction of pegylated interferon alpha-2a in the treatment of chronic hepatitis C.

AIM: We conducted a trial to evaluate whether eight-week oral administration of meloxicam, a non-steroidal anti-inflammatory drug, would decrease the rate of the patients who required dose reduction of pegylated interferon alpha-2a in the treatment of chronic hepatitis C. METHODS: Sixty patients given weekly subcutaneous administration of pegylated interferon alpha-2a at a dose of 180 mug for 48 weeks were allocated into the meloxicam group (n = 22) and the control group (n = 38) before interferon treatment. Meloxicam was given orally at a dose of 10 mg once a day for eight weeks from the start of interferon treatment. RESULTS: The cumulative rate of dose-reduction-free patients was significantly higher in the meloxicam group (P < 0.05). Until week eight, 44.7% of the control group and 9.1% of the meloxicam group required dose reduction. Dose was modified by neutropenia in 31.6% and 18.2% of the control and meloxicam groups, respectively. Meloxicam relieved a declineof neutrophil count within the first eight weeks from 54.2% to 44.2% (P < 0.05). Multivariate analysis revealed that greater pretreatment neutrophil count and the use of meloxicam were independent factors associated with avoiding dose reduction. Sustained virological response was obtained in 52.6% of the patients. The multivariate logistic analysis revealed that viral serotype and viral load were the only independent factors associated with sustained virological response. CONCLUSION: Eight-week administration of meloxicam prevented dose reduction of pegylated interferon by relieving a decline of neutrophil count in the treatment of chronic hepatitis C.

Synthesis of the metabolites of 4-(2-methyl-1H-imidazol-1-yl)-2,2-diphenylbutanamide (KRP-197/ONO-8025).

We synthesized the six presumed metabolites (2--7) of 4-(2-methyl-1H-imidazol-1-yl)-2,2-diphenylbutanamide [KRP-197/ONO-8025, 1], a urinary incontinence therapeutic agent, in order to confirm the structures of the metabolites. Metabolite (2) was synthesized via glucuronidaion of compound (1) and methyl 2,3,4-tri-O-benzoyl-1-methanesulfonyl-alpha-D-glucopyranuronate. Metabolite (3) was synthesized via 3-(tert-butoxycarbonyl)-2-methyl-1,3-imidazolidine-4,5-dione. Metabolites (4--7) were synthesized via 4-amino-2-diphenylbutanamide, respectively. The structures of the metabolites (2--7) in humans were identified by means of synthesis of the authentic compounds.

Comparison of body composition measurements obtained by two fan-beam DXA instruments.

Although dual-energy X-ray absorptiometry (DXA) has been widely used for measuring body composition, discrepancies have been reported to exist among results obtained from different instruments. In the course of longitudinal studies lasting for many years, old instruments may be required to be replaced with new ones, necessitating comparison and validation between the values obtained by the old and new instruments. We compared the data obtained by the two fan-beam DXA instruments, QDR-2000 (Hologic, Waltham, MA) and Delphi (Hologic). Body composition was first measured by the Hologic QDR-2000 and next by the Delphi W within 30 days in 99 healthy subjects. Whole-body fat mass (FM), percentage of FM, arm FM, and leg FM measured by the Hologic QDR-2000 were significantly larger than those measured by the Delphi W. Lean tissue mass (LTM), bone mineral content, and bone mineral density of the whole body, trunk FM, arm LTM, and leg LTM measured by the QDR-2000 were significantly smaller than those measured by the Delphi W. After converting the QDR-2000 values by equations developed by multiple regression analysis, they were not significantly different from the corresponding Delphi values. Measurements by the QDR-2000 and the Delphi W were not interchangeable and the conversion equations reduced the discrepancy to a level that enabled direct comparison of the data obtained by the two instruments. However, cautious interpretation is necessary when the conversion equations are applied to other instruments even of the same type or when evaluating data of individual subjects.

Increase in the prevalence of fatty liver in Japan over the past 12 years: analysis of clinical background.

BACKGROUND: The aim of this investigation was to elucidate the time-course of changes in the prevalence of fatty liver, and to analyze its clinical backgrounds over the previous 12-year period. METHODS: Thirty-nine thousand one hundred and fifty-one individuals who visited the Tokai University Hospital Health Checkup Center from 1989 to 2000 were examined for the presence of fatty liver, and their clinical backgrounds were analyzed. RESULTS: In 1989, the prevalence of fatty liver was 12.6%, and it rose gradually thereafter, reaching 30.3% in 1998, corresponding to a 2.4-fold increase over the prevalence rate in 1989. The average prevalence was about twice as high in males (26.0%) as in females (12.7%). The prevalence was uniformly high in males in all ages, while the prevalence in females tended to rise gradually with age. Body mass index (BMI) was found to be the variable most closely related to the onset of fatty liver. On the other hand, nonobese individuals with a BMI of less than 25 kg/m(2) accounted for approximately half of all the patients with fatty liver, and this proportion remained almost unchanged during the 12-year survey period. It was therefore difficult to simply attribute the increase in the prevalence of fatty liver to the increased prevalence of obesity. In the 35 519 repeat examinees (repeaters), it was found that 5088 individuals (14.3%) developed fatty liver, and fatty liver resolved in 1248 individuals (3.5%). As fatty liver developed, the BMI increased by 1.0 +/- 1.3 kg/m(2). As fatty liver disappeared, the BMI decreased by 1.0 +/- 1.5 kg/m(2). CONCLUSIONS: These results suggest that the absolute value of the BMI, as well as the relative changes in the BMI in each individual, may be related to the onset of fatty liver. The aim of this investigation was to elucidate the time-course of changes in the prevalence of fatty liver, and to analyze its clinical backgrounds over the previous 12-year period.