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ABSTRACT: Background: Sorafenib is the first molecular-targeted agent that is effective for advanced hepatocellular carcinoma (HCC), with prolongation of survival. However, a complete response is very rare, and rapid regression of HCC after short-term treatment with sorafenib has not been reported previously. Case Reports: We describe 2 patients with advanced multiple HCC who received sorafenib for short periods of 1 or 2 weeks, respectively. Longer treatment was precluded by the development of hepatic failure as an adverse event of sorafenib. Results: HCC rapidly regressed, and both patients had a partial response (PR), despite short-term treatment. Furthermore, an early elevation of des-gamma-carboxy prothrombin (DCP) was temporarily seen in both patients, with no elevation of alpha-fetoprotein. Conclusions: Sorafenib can induce rapid regression of advanced HCC even after short-term treatment, and the initial response of HCC was identical in both patients. Since early elevation of DCP was observed in our patients with PR, DCP might be a predictive biomarker of anti-tumor response. Further studies are required to clarify the mechanisms underlying the effectiveness of sorafenib, including the alteration of DCP.
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ABSTRACT: BACKGROUND: To determine the value of early alterations of the tumor markers α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) for predicting the outcomes of patients with advanced hepatocellular carcinoma (HCC) who receive sorafenib. MATERIALS AND METHODS: Tumor response, overall survival (OS), and progression-free survival (PFS) were retrospectively analyzed in 59 patients with advanced HCC. Serum AFP and DCP were examined for early elevation within 4 weeks after the initiation of sorafenib. An increase in AFP was defined as AFP of more than 20%, and an increase in DCP was defined as more than two-fold higher level than the baseline. The relationship of the clinical characteristics, laboratory data at baseline, and early elevations of AFP and DCP with disease progression was analyzed. RESULTS: The median OS and PFS were 11 and 3.3 months, respectively. The rate of progressive disease (PD) was 54%, and an early increase in AFP was significantly related to PD (P=0.006) and was a significant independent predictor of both poorer OS and PFS (P<0.001, hazard ratio, 4.14; 95% confidence interval, 1.946-8.811; and P=0.001, hazard ratio, 2.852; 95% confidence interval, 1.524-5.337, respectively). There was no association between early increase in DCP and clinical outcomes. CONCLUSION: Early increase in AFP predicted PD and poorer survival and may thus be a useful biomarker in patients with advanced HCC who receive sorafenib.
European journal of gastroenterology & hepatology 02/2013; · 1.66 Impact Factor
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Hisashi Hidaka,
Takahide Nakazawa,
Shinji Kutsukake,
Yoshiki Yamazaki,
Izumi Aoki,
Shiro Nakano,
Noriyuki Asaba,
Tsutomu Minamino,
Juichi Takada,
Yoshiaki Tanaka,
Yusuke Okuwaki,
Masaaki Watanabe, Akitaka Shibuya,
Wasaburo Koizumi
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ABSTRACT: BACKGROUND: Nocturnal administration of branched-chain amino acid (BCAA) granules improves serum albumin levels in patients with cirrhosis. However, it is unclear whether or not this administration method can improve the patients' quality of life (QOL). In this study, we aimed to investigate the efficacy of BCAA granules, given nocturnally, in improving QOL in these patients. METHODS: We performed a multicenter, randomized controlled trial examining the comparative effects of BCAA granules given orally for 3 months with daytime or nocturnal administration in patients with compensated cirrhosis. Health-related QOL was measured by a Japanese version of the questionnaire on subjective and objective symptoms, and the Short Form-8 (SF-8) questionnaire. RESULTS: Twenty-one patients received BCAA granules three times a day (one sachet after each meal: the daytime group), and 16 patients received the granules twice a day (one sachet after breakfast, and two sachets before bedtime: the nocturnal group). Baseline characteristics did not differ between the groups (whole cohort: Child-Pugh grade A/B, 21/16; mean age, 68.2 years). There was no significant difference in any of the subjects revealed by the questionnaire regarding subjective or objective symptoms, or by the SF-8 between the daytime group and the nocturnal group after 3 months of treatment. The daytime group showed a significant effect on general health, vitality, social functioning, mental health, and role emotional as revealed on the SF-8. Conversely, the nocturnal group exhibited a significant decrease in the occurrence of muscle cramps in the legs (P = 0.014) and significantly improved Fisher's ratio after 3 months (P = 0.04). CONCLUSIONS: Nocturnal administration of BCAA granules in patients with cirrhosis reduced the occurrence of muscle cramps in the leg but did not improve the patients' QOL.
Journal of Gastroenterology 07/2012; · 4.16 Impact Factor
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Satoshi Kobayashi,
Shinichi Ohkawa,
Masaaki Kondo,
Manabu Morimoto,
Kazushi Numata,
Koutaro Matsunaga,
Chiaki Okuse,
Michihiro Suzuki,
Hiroshi Hidaka,
Juichi Takada,
Yusuke Okuwaki, Akitaka Shibuya,
Katsuaki Tanaka
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ABSTRACT: Some clinical studies confirmed the efficacy and safety of sorafenib in advanced hepatocellular carcinoma(HCC), for which the standard initial dose is 400 mg twice daily. However, it is unclear whether this dosage is tolerable for patients with a low body surface area(BSA). We retrospectively analyzed the difference in efficacy and safety of sorafenib between patients with low BSA and high BSA.
From July 2009 to June 2010, 64 patients with Child-Pugh grade A cirrhosis receiving sorafenib at 4 institutions were enrolled, and divided into two groups(BSA<1. 6m2 and ≥1. 6m2).
In BSA<1. 6m2 and BSA≥1. 6m2 groups, grade 3-4 adverse events were observed in 64. 3% and 55. 3% of patients, respectively, and subsequent discontinuation was 38. 5% and 24. 2%, respectively indicating poor compliance in the former group. The disease control rate was 33. 3% and 37. 8%, the median time-to-radiological progression(TTRP)was 2. 1 months and 3. 6 months(p=0. 003), and median survival time was 6. 6 months and 11. 2 months in low BSA and high BSA groups(p=0. 10), respectively. Multi-variate analysis showed that poor prognostic factors for TTRP were ECOG performance status of ≥1 and BSA<1. 6m2.
Standard dosage seems intolerable for patients with low BSA, and results in poor prognosis.
Gan to kagaku ryoho. Cancer & chemotherapy 07/2012; 39(7):1065-70.
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ABSTRACT: Sorafenib is currently in clinical use as an oral multikinase inhibitor that blocks tumor growth and cell proliferation in advanced hepatocellular carcinoma (HCC). It has been demonstrated in a translating study that sorafenib had a beneficial effect on portocollateral circulation in cirrhotic animals with portal hypertension. This study was prospectively performed to evaluate the portal hemodynamic effect of sorafenib in patients with advanced HCC using duplex Doppler ultrasonography (DDU).
Twenty-five Child-Pugh class-A patients with advanced HCC had received sorafenib at a dose of 400 mg twice daily. Primary outcomes were changes in portal venous area (PVA; cm(2)) as seen by using DDU before and after a 2-week administration of sorafenib. Secondary outcomes included the changes of laboratory data and other flow data revealed on DDU.
PVA was significantly decreased after a 2-week administration (0.78 ± 0.23 vs. 0.64 ± 0.25, P = 0.023), while the portal venous flow velocity (PVV; cm/s) was not significantly changed (0.22 ± 0.06 vs. 0.24 ± 0.07, P = 0.17). Therefore, the congestion index (PVA/PVV), which reflects the pathophysiological hemodynamics of portal venous system, was significantly decreased (3.9 ± 1.7 vs. 3.0 ± 1.4, P = 0.042).
We demonstrated the portal hemodynamic effect of sorafenib in patients with advanced HCC. Considering that this was a short-term study, because sorafenib could be a potential beneficial therapeutic agent for portal hypertension, it will be necessary to verify its clinical benefits for portal hypertension in future studies.
Journal of Gastroenterology 03/2012; 47(9):1030-5. · 4.16 Impact Factor
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ABSTRACT: In environments in which professional nurses do simple tasks, e.g., laundry, cleaning, and waste disposal, they cannot concentrate on technical jobs by utilizing their expertise to its fullest benefit. Particularly, in Japan, the nursing shortage is a serious problem. If professional nurses take their time to do any of these simple tasks, the tasks should be preferentially allocated to nursing assistants. Because there has been no descriptive study to investigate the amount of time Japanese professional nurses spent doing such simple tasks during their working time, their actual conditions remain unclear. Professional nurses recorded their total working time and the time they spent doing such simple tasks during the week of the survey period. The time an individual respondent spent doing one or more simple tasks during that week was summed up, as was their working time. Subsequently, the percentage of the summed time he or she spent doing any of those tasks in his or her summed working time was calculated. A total of 1,086 respondents in 19 hospitals that had 87 to 376 beds were analyzed (response rate: 53.3%). The average time (SD) that respondents spent doing those simple tasks and their total working time were 2.24 (3.35) hours and 37.48 (10.88) hours, respectively. The average percentage (SD) of the time they spent doing the simple tasks in their working time was 6.00% (8.39). Hospital administrators must decrease this percentage. Proper working environments in which professional nurses can concentrate more on their technical jobs must be created.
The Tohoku Journal of Experimental Medicine 01/2012; 228(1):59-67. · 1.24 Impact Factor
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ABSTRACT: In the past, no effective systemic therapy has existed for patients with advanced hepatocellular carcinoma. Sorafenib, an oral multikinase inhibitor, has recently been shown to improve overall survival in patients with advanced hepatocellular carcinoma in two randomized, double-blinded, placebo-controlled trials. This drug has been approved as the first-line therapy for advanced hepatocellular carcinoma patients. We report an intriguing case of advanced hepatocellular carcinoma in which the patient achieved late- onset partial response by prolonged administration of sorafenib in spite of progressive disease.
A 54-year-old Japanese man was treated with sorafenib for multiple lung metastases after surgical resection for advanced hepatocellular carcinoma accompanied by vascular invasion of the left branch of the portal vein. Although the effective diagnosis was progressive disease, almost all sites began to reduce or disappear eight months after the diagnosis of progressive disease. A dramatic reduction in alpha-fetoprotein and des-gamma-carboxy prothrombin levels was observed. The patient finally achieved partial response and his status remains unchanged.
If tolerated, prolonged sorafenib treatment may be beneficial.
Journal of Medical Case Reports 01/2012; 6:38.
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Tsutomu Minamino,
Yoshiya Ito,
Hirotoki Ohkubo,
Kanako Hosono,
Tatsunori Suzuki,
Takehito Sato,
Takako Ae, Akitaka Shibuya,
Hiroyuki Sakagami,
Shuh Narumiya,
Wasaburo Koizumi,
Masataka Majima
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ABSTRACT: It is thought that thromboxane A(2) (TxA(2)) contributes to the progression of inflammation during acute hepatic injury; however, it is still unknown whether TxA(2) is involved in liver repair. The objective of the present study was to examine the role of TxA(2) receptor (TP) signaling in liver injury and repair in response to toxic injury. Carbon tetrachloride (CCl(4)) was used to induce liver injury in TP knockout (TP(-/-)) mice and wild-type (WT) mice. In WT mice, serum levels of alanine aminotransferase (ALT) and the size of the necrotic area peaked at 24 and 48h, respectively, and then declined. In TP(-/-) mice, the changes in ALT levels were similar to WT mice, but liver regeneration was impaired as evidenced by remained elevated levels of hepatic necrosis and by delayed hepatocyte proliferation, which was associated with the reduced expression of growth factors including interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), and hepatocyte growth factor (HGF). In TP(-/-) mice, the accumulation of hepatic CD11b(+)/F4/80(+) macrophages in injured livers was attenuated, and the hepatic expression of monocyte chemoattractant protein-1 (MCP-1/CCL2) and its receptor, the C-C chemokine receptor (CCR2), was reduced compared to WT. Additionally, the application of the TP receptor agonist, U-46619, enhanced the expression of MCP-1/CCL2 and CCR2 in peritoneal macrophages, which was associated with increased levels of IL-6, TNFα and HGF. These results suggested that TP receptor signaling facilitates liver recovery following CCl(4)-induced hepatotoxicity by affecting the expression of hepatotrophic growth factors, and through the recruitment of macrophages mediated by MCP-1/CCL2-CCR2 expression.
Toxicology and Applied Pharmacology 12/2011; 259(1):104-14. · 4.45 Impact Factor
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Masaaki Watanabe,
Sumie Ogasawara,
Akihiko Takahashi,
Juichi Takada,
Yoshiaki Tanaka,
Yusuke Okuwaki,
Tsutomu Minamino,
Hisashi Hidaka,
Takahide Nakazawa, Akitaka Shibuya,
Wasaburo Koizumi
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ABSTRACT: A 62-year-old male treated with pegylated interferon α-2b plus ribavirin for chronic hepatitis C complained of sudden painless decreased visual acuity. This patient was diagnosed as having simultaneous occlusions of the branch retinal artery and central retinal vein, although he had no history of major risk factors for retinal vessel (artery and vein) occlusion. Unfortunately, visual acuity did not completely recover. Furthermore, the patient was heterozygous for interleukin (IL) 28B genetic polymorphisms. The etiology of interferon-associated retinal vessel occlusion is not yet clear. However, a review based on previous case reports suggested that some factors including ribavirin might act as a risk or cause of retinal vessel occlusion.
Cutaneous and Ocular Toxicology 12/2011; 31(3):253-7. · 0.91 Impact Factor
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Hisashi Hidaka,
Takahide Nakazawa,
Guoqin Wang,
Shigehiro Kokubu,
Tsutomu Minamino,
Juichi Takada,
Yoshiaki Tanaka,
Yusuke Okuwaki,
Masaaki Watanabe,
Satoshi Tanabe, Akitaka Shibuya,
Wasaburo Koizumi
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ABSTRACT: Elective esophageal variceal ligation (EVL) is performed to decrease the risk of variceal hemorrhage. EVL is associated with adverse effects, including post-ligated bleeding, chest pain, and dysphagia. Proton pump inhibitors (PPIs) are the most potent pharmacological agents for inhibition of gastric acid secretion. However, the long-term effect of PPIs after EVL remains unclear. The aim of this study was to assess the efficacy of rabeprazole, a PPI, after variceal eradication by EVL.
We performed a randomized, controlled trial in Kitasato University East Hospital. The primary endpoint was treatment failure, defined as variceal hemorrhage or severe medical complications. Between July 2007 and September 2010, 43 patients were randomized into this study and followed up until September 2010.
Twenty-one patients in the rabeprazole arm received 10 mg rabeprazole daily after EVL, and 22 patients in the control received no antisecretory treatment from the same stage. Baseline characteristics did not differ between the groups (median Child-Pugh score, 6; median age, 62 years; median follow-up, 18.7 months). The trial was stopped early after an interim analysis showed that the risk of bleeding and failure of rabeprazole treatment was lower than that of no antisecretory treatment with the log-rank test showing a significant difference between the groups (P = 0.007) and a hazard ratio of 0.098 [95% confidence interval, 0.012-0.79 (P = 0.029)].
Long-term administration of PPIs reduced the risk of treatment failure after EVL. Acid suppression therapy should also be considered as a treatment option after EVL.
Journal of Gastroenterology 09/2011; 47(2):118-26. · 4.16 Impact Factor
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ABSTRACT: The renin-angiotensin system plays an important role in hepatic fibrosis and portal hypertension. We evaluated the long-term effects of olmesartan, an angiotensin type 1 (AT1) receptor blocker, on hemodynamics and liver fibrosis.
Forty-eight selected patients with cirrhosis were randomly divided into two groups of 24 patients each, those who received and those who did not receive olmesartan treatment for 1 year. Hepatic hemodynamic studies, and measurements of transforming growth factor-beta1 (TGF-beta1) and blood markers of hepatic fibrosis, including serum hyaluronic acid (HA), type IV collagen, and procollagen III N-terminal propeptide levels, were also performed at the beginning and end of the study.
The median dose of the final drug administration was 20 mg (range 10-40 mg). Olmesartan reduced the hepatic venous pressure gradient (HVPG) by -12.9 ± 9.1% (p = 0.035) after 1 year. No significant changes were seen in controls. Six of the 24 patients (25%) in the olmesartan group showed a >20% reduction of HVPG from baseline values. TGF-beta1 was significantly decreased in patients who received olmesartan (7.0 ± 8.2 vs. 3.1 ± 1.6 ng/mL, p = 0.046) but there was no decrease in the controls. A significant trend was shown by correlating HA and TGF-beta1 variations in cirrhosis patients (p = 0.018, r = 0.377). Fibrosis markers were unchanged at the end of the study in both groups.
Olmesartan induced a mild reduction of portal pressure and TGF-beta1 for 1 year, but did not suppress hepatic fibrosis markers.
Journal of Gastroenterology 08/2011; 46(11):1316-23. · 4.16 Impact Factor
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Masaaki Watanabe, Akitaka Shibuya,
Yuhko Tsunoda,
Mikio Danbara,
Ryuji Ishii,
Manabu Ohsaka,
Juichi Takada,
Yoshiaki Tanaka,
Yusuke Okuwaki,
Tsutomu Minamino,
Hisashi Hidaka,
Takahide Nakazawa,
Ryouichi Horie,
Masaaki Higashihara,
Wasaburo Koizumi
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ABSTRACT: De novo hepatitis B virus (HBV)-related hepatitis is a well-known fatal complication following chemo-immunosuppressive therapy in patients with past HBV infection (HB surface antigen and serum HBV DNA negative, but HB core antibody and/or HB surface antibody positive). This research was conducted to evaluate the incidence of and clinical features associated with re-appearance of serum HBV DNA following chemo-immunosuppressive therapy in Japanese patients with past HBV infection.
This is a retrospective review. Forty-five patients with past HBV infection who had received chemo-immunosuppressive therapy for haematological disease were followed up for >6 months, to determine whether the serum test for HBV changed from negative to positive (i.e. re-appearance of serum HBV DNA following chemo-immunosuppressive therapy).
Re-appearance of serum HBV DNA was confirmed in five (20.8%) of the 24 patients who had received treatment regimens containing rituximab, but in none of the 21 patients who had not received treatment regimens containing rituximab (P=0.035). The HBV genotype could be determined in four of the five aforementioned patients, and in all four, HBV genotype C, which is the most prevalent genotype in Japan, was identified.
This research showed that re-appearance of serum HBV DNA is not rare in Japanese patients treated with chemotherapy regimens containing rituximab, and no other factors related to such re-appearance of serum HBV DNA could be identified. Well-designed clinical studies, including immunological and genetic analyses of the host and of the HBV, are required for further elucidation.
Liver international: official journal of the International Association for the Study of the Liver 03/2011; 31(3):340-7. · 3.82 Impact Factor
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Manabu Morimoto,
Kazushi Numata,
Masaaki Kondo,
Hisashi Hidaka,
Juichi Takada, Akitaka Shibuya,
Satoshi Kobayashi,
Shinichi Ohkawa,
Chiaki Okuse,
Satoshi Morita,
Masataka Taguri,
Katsuaki Tanaka
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ABSTRACT: Aim: Sorafenib is approved for the treatment of advanced hepatocellular carcinoma (HCC) in Japan; however, its tolerability and efficacy in elderly patients with HCC have not been clarified. We aimed to evaluate the tolerability and efficacy of sorafenib with increasing age.Methods: As part of a retrospective, multicenter cohort study conducted between May 2009 and February 2010, patients with advanced HCC received 400 mg sorafenib twice daily (standard dosage) or once daily (half-dosage) until disease progression or treatment intolerance.Results: The mean age of the enrolled patients (n = 76) was 70.3 years, and 24 of them were ≥75 years old. The prognostic factors for survival were age < 75 years, performance status score zero, -fetoprotein level < 1000 ng/mL, des-gamma-carboxy prothrombin level < 1000 ng/mL, and treatment duration ≥ 1 month. The median treatment duration and overall incidence of adverse drug reactions (ADRs) were not statistically different with increasing age. However, subgroup analysis revealed that treatment discontinuation because of ADRs was more frequent among the ≥75-year-old patients (41.7%) than among the <75-year-old ones (15.0%) with the standard dosage (P = 0.047); this trend was not observed among those who received the half-dose regimen.Conclusions: Sorafenib has modest efficacy and acceptable toxicity in younger (<75 years) patients with HCC; however, elderly patients experience some side effects when it is administered at the standard dosage.
Hepatology Research 02/2011; 41(4):296 - 302. · 2.20 Impact Factor
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ABSTRACT: Nursing assistants can work without a professional certification to help registered nurses and licensed practical nurses. Nursing assistants engage in various tasks, e.g., washing laundry, cleaning up, and clerk tasks regarding nursing. Enhancing work motivation among nursing assistants is essential for every hospital, because when nursing assistants do their jobs well, it allows registered nurses and licensed practical nurses to complete their own specialized jobs. We examined the predictors significantly associated with nursing assistants' work motivation. For those predictors, we produced items to examine job satisfaction. Those items are classified into intrinsic and extrinsic facets. The subjects for this study were Japanese nursing assistants working in 26 hospitals with 62-376 beds (4 public and 22 private hospitals). A total of 516 nursing assistants were analyzed, with the average age and standard deviation of 42.7 ± 12.9 years; the age of 456 female subjects was 43.8 ± 12.7 years and that of 60 male subjects was 34.3 ± 11.0 years. Our results show that "work motivation" is significantly associated with "free time to do one's own things," "nursing assistants as important partners on the job," "feeling helpful to patients," "participating in decision making," and "job-skill improvement." Free time to do one's own things is an extrinsic item. Hospital administrators must monitor the workload and their quality of life among nursing assistants. All the other significant items are intrinsic. Nursing assistants are not only motivated by money. They highly value the intrinsic nature and experience of their jobs.
The Tohoku Journal of Experimental Medicine 01/2011; 225(4):293-300. · 1.24 Impact Factor
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ABSTRACT: In medical education, it is important for medical students to develop their ethics to respect patients' rights. Some physicians might make light of patients' rights, because the increased awareness of such rights might make it more difficult for them to conduct medical practice. In the present study, predictors significantly associated with "a sense of resistance to patients' rights" were examined using anonymous self-administered questionnaires. For these predictors, we produced original items with reference to the concept of ethical development and the teachings of Mencius. The subjects were medical students at the Kitasato University School of Medicine, a private university in Japan. A total of 518 students were analyzed (response rate, 78.4%). The average age of enrolled subjects was 22.5 ± 2.7 years (average age ± standard deviation). The average age of 308 male subjects was 22.7 ± 2.8 years, while that of 210 female subjects was 22.1 ± 2.5 years. The item, "Excessive measures to pass the national examination for medical practitioners," was significantly associated with "a sense of resistance to patients' rights." However, other items, including basic attributes such as age and gender, were not significant predictors. If students spent their school time only focusing on the national examination, they would lose the opportunity to receive the ethical education that would allow them to respect patients' rights. That ethical development cannot easily be evaluated with written exams. Thus, along with the acquisition of medical knowledge, educational programs to promote medical students' ethics should be developed.
The Tohoku Journal of Experimental Medicine 01/2011; 224(4):307-15. · 1.24 Impact Factor
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Hisashi Hidaka,
Takahide Nakazawa,
Guoqin Wang,
Shigehiro Kokubu,
Tsutomu Minamino,
Juichi Takada,
Yoshiaki Tanaka,
Yusuke Okuwaki,
Masaaki Watanabe, Akitaka Shibuya,
Wasaburo Koizumi
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ABSTRACT: Aim: We prospectively evaluated the reliability and validity of splenic volume with 3-D ultrasound measurement and clarified its clinical usefulness. Methods: Thirty healthy volunteers and 30 patients with cirrhosis were included in this study. All 3-D ultrasound examinations of splenic volumes were performed twice by two experienced sonographers with transabdominal ultrasound using virtual organ computer-aided analysis (VOCAL). Reliability was confirmed among all subjects by evaluating within-observer repeatability and between-observer reproducibility using intraclass correlation coefficients (ICC) and Bland-Altman plots. Overall between-instrument agreement of the measurements and computed tomography (CT) volumetry among cirrhotic patients were performed to determine validity. Results: For all 240 examinations, 3-D ultrasound visualization and measurement of the spleen volume was possible. Mean spleen volume was 104.0 mL for the volunteers and 283.5 mL for the cirrhotic patients. The repeatability was high, with ICC (95% confidence interval) of 0.996 (0.993-0.997) for observer A and 0.997 (0.994-0.998) for observer B. Moreover, the interobserver ICC was 0.996, indicating high reproducibility. Despite the difference in volume between the volunteers and cirrhotic patients, sensitivity analyses indicated consistent results for both groups. Regarding the validity of the 3-D ultrasound measurement, it also showed moderate to high agreement with CT volumetry, with mean ICC of 0.922 and 0.924 for observers A and B, respectively. The reliability and validity results from the Bland-Altman plots were similar to those from the ICC, with limits of agreement consistently narrow from a clinically practical view. Conclusion: 3-D ultrasound measurements using VOCAL are valid and reliable in spleen volume examinations.
Hepatology Research 10/2010; 40(10):979-88. · 2.20 Impact Factor
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ABSTRACT: Hepatitis B virus (HBV) reactivation is a fatal complication in patients who receive chemotherapy or immunosuppressive therapy. We examined the effect of preventive entecavir (ETV), a new nucleoside analogue on HBV reactivation during chemotherapy or immunosuppressive therapy.
Between February 2007 and September 2009, sixteen nucleoside analogue treatment-naive patients with chronic HBV infection (HB surface antigen [HBsAg] positive) who required chemotherapy or immunosuppressive therapy were enrolled. Referring to some guidelines, the patients received preventive ETV to reduce incidence of HBV reactivation, and were closely monitored for HBV markers.
HBV reactivation did not occur in any of the 16 patients and the indispensable treatments for their underlying diseases could be continued. However, HBV relapsed after preventive ETV was discontinued in 2 patients.
This study suggests that ETV is a useful option for preventing HBV reactivation in patients with chronic HBV infection.
European Journal of Internal Medicine 08/2010; 21(4):333-7. · 2.00 Impact Factor
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ABSTRACT: Sorafenib is the first molecular-targeted agent that is effective for advanced hepatocellular carcinoma (HCC), with prolongation of survival. However, a complete response is very rare, and rapid regression of HCC after short-term treatment with sorafenib has not been reported previously.
We describe 2 patients with advanced multiple HCC who received sorafenib for short periods of 1 or 2 weeks, respectively. Longer treatment was precluded by the development of hepatic failure as an adverse event of sorafenib.
HCC rapidly regressed, and both patients had a partial response (PR), despite short-term treatment. Furthermore, an early elevation of des-gamma-carboxy prothrombin (DCP) was temporarily seen in both patients, with no elevation of alpha-fetoprotein.
Sorafenib can induce rapid regression of advanced HCC even after short-term treatment, and the initial response of HCC was identical in both patients. Since early elevation of DCP was observed in our patients with PR, DCP might be a predictive biomarker of anti-tumor response. Further studies are required to clarify the mechanisms underlying the effectiveness of sorafenib, including the alteration of DCP.
Case Reports in Oncology 01/2010; 3(2):298-303.
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ABSTRACT: Intrahepatic distant recurrence (IDR) of hepatocellular carcinoma (HCC) after curative treatment occurs frequently and influences the prognoses. The aim of this study was to determine prognostic factors affecting survival after IDR and the optimum therapy for IDR.
A total of 115 patients with a single small primary HCC who had complete radiofrequency (RF) ablation were enrolled in this study. The prognostic factors and the optimum therapy affecting survival were statistically analyzed among patients with IDRs.
IDRs were observed in 59 (51.3%) patients with the median observation period of 19.6 months. The cumulative rates of IDRs were 11.8, 53.9, and 75.8% at 1, 3, and 5 years, respectively. IDR nodules were present as a single nodule in 38 patients and as multiple nodules in 21 patients. In all, 23 patients died during the follow-up. A total of 30 patients were treated with RF ablation, and 27 were treated with transcatheter arterial chemoembolization (TACE). The overall cumulative survival rates after IDRs were 92.7, 55.4, and 43.7% at 1, 3, and 5 years, respectively. A multivariate analysis showed that treatment with RF ablation for IDR was a significant favorable prognostic factor after IDR (hazard ratio: 0.167, 95% confidence interval: 0.048-0.584, P=0.005). In a comparison of survival after IDR between patients treated with RF ablation and TACE, who were comparable with clinical and tumoral characteristics, the cumulative survival rate of patients treated with RF ablation was significantly higher than that of those treated with TACE (77.2 vs 28.5% at 3 years). The cumulative survival rates obtained from the initial RF ablation of the patients with IDRs treated with repeat RF ablation were similar to those of recurrence-free patients.
Repeat RF ablation should be attempted for IDR as much as possible despite tumor multiplicity for survival benefit; by reducing the need, it will help solve the problem of the current shortage of donors for liver transplantations.
The American Journal of Gastroenterology 08/2009; 104(11):2747-53. · 7.28 Impact Factor
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Atsushi Tanaka,
Saeko Nezu,
Satoko Uegaki,
Kentaro Kikuchi, Akitaka Shibuya,
Hiroshi Miyakawa,
Shin-ichi Takahashi,
Ilaria Bianchi,
Paola Zermiani,
Mauro Podda,
Hiromasa Ohira,
Pietro Invernizzi,
Hajime Takikawa
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ABSTRACT: Vitamin D receptor (VDR) agonists have recently been identified as potent immunomodulators capable of inhibiting Th1-mediated immune response, leading us to consider the hypothesis that functional VDR polymorphisms might contribute to enhanced risk for developing primary biliary cirrhosis (PBC), a Th1-mediated autoimmune disease. In the current study, we aimed at elucidating the genetic association of VDR polymorphisms with susceptibility to PBC in Japanese and Italian populations.
We enrolled 334 PBC patients (195 Japanese and 139 Italians), as well as 334 age- and sex-matched controls (179 Japanese and 156 Italians). VDR genotyping was performed by PCR-RFLP, using BsmI, ApaI and TaqI endonucleases.
The genotype BB of BsmI polymorphism was significantly associated with PBC (OR = 1.80 [95% CI; 1.19-2.73], p = 0.005). The association of the genotype BB was observed in Japanese (OR = 13.77, p = 0.001), and Italians (OR = 1.83, p = 0.019), respectively, although not significant in Italians after Bonferroni correction. The frequency of the B allele at the BsmI polymorphism was significantly higher in PBC patients (OR = 1.27 [95% CI; 1.02-1.59], p = 0.040).
The genotype 'BB' as well as 'B' allele at BsmI polymorphism of the VDR gene contribute to the risk of PBC development.
Journal of Hepatology 04/2009; 50(6):1202-9. · 9.26 Impact Factor
