Biomedical subjects
Shinichi Ohkawa
Publications and source records attributed to Shinichi Ohkawa.
A phase II study of weekly irinotecan as first-line therapy for patients with metastatic pancreatic cancer.
PURPOSE: The aim of this study was to assess the efficacy and toxicity of weekly irinotecan in patients with metastatic pancreatic cancer. PATIENTS AND METHODS: Patients with histologically proven pancreatic adenocarcinoma, at least one bidimensionally measurable metastatic lesion, and no prior chemotherapy were selected. Irinotecan at a dose of 100 mg/m2 was administered intravenously for 90 min on days 1, 8, and 15 every 4 weeks until disease progression or unacceptable toxicity. Pharmacokinetics was examined on day 1 of the first cycle of treatment. RESULTS: Thirty-seven of 40 enrolled patients were assessable for efficacy and toxicity. A partial response was obtained in 10 patients, giving an overall response rate of 27.0% (95% confidence interval 13.8-44.1%). The median overall survival was 7.3 months with a 1-year survival rate of 29.5%. Although toxicities were generally tolerated, one patient died of disseminated intravascular coagulation syndrome induced by neutropenia with watery diarrhea. Pharmacokinetic study showed that patients with biliary drainage seemed to have higher area under the concentration versus time curve for irinotecan and its metabolites compared with patients without biliary drainage. CONCLUSION: Single-agent irinotecan has significant efficacy for metastatic pancreatic cancer. The toxicity with this schedule appears manageable, though it must be monitored carefully.
Randomized, double-blind, placebo-controlled trial of bovine lactoferrin in patients with chronic hepatitis C.
Several studies have suggested that lactoferrin administration may decrease the serum level of hepatitis C virus (HCV) RNA in patients with chronic hepatitis C. The aim of the present study was to confirm the efficacy of orally administered bovine lactoferrin (bLF) in patients with chronic hepatitis C. The patients with chronic hepatitis C randomly received either oral bLF at a dose of 1.8 g daily for 12 weeks, or an oral placebo. The primary endpoint was the virologic response, defined as a 50% or greater decrease in serum HCV RNA level at 12 weeks compared with the baseline. The secondary endpoint was the biochemical response, which was defined as a 50% or greater decrease in the serum alanine aminotransferase (ALT) level at 12 weeks compared with the baseline. One hundred and ninety-eight of 199 patients were evaluable for efficacy and safety. bLF treatment was well tolerated and no serious toxicities were observed. A virologic response was achieved in 14 of 97 patients (14.4%) in the bLF group, and 19 of 101 (18.8%) in the placebo group. There was no significant difference in virologic response rates between the two groups (-4.4%, 95% confidence interval -14.8, 6.1). In addition, bLF intake did not have any favorable effect on the serum ALT level. The virologic responses were not different between two groups in any subgroup analysis. In conclusion, orally administered bLF does not demonstrate any significant efficacy in patients with chronic hepatitis C.
[Gemcitabine chemotherapy for patients with advanced or relapsed pancreatic cancer].
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Phase II study of single-agent gemcitabine in patients with advanced biliary tract cancer.
PURPOSE: This phase II study was conducted to evaluate the efficacy and toxicity of single-agent gemcitabine in patients with advanced or metastatic biliary tract cancer. PATIENTS AND METHODS: Gemcitabine 1,000 mg/m(2) was administered as an intravenous 30-min infusion on days 1, 8, and 15 for every 28 days. RESULTS: Forty chemonaive patients with a median age of 61 (range 33-73) were enrolled, and all 40 patients were involved in efficacy and safety analyses. Seven (17.5%) achieved partial response; 15 (37.5%) had stable disease; 17 (42.5%) had progressive disease; and 1 (2.5%) was not evaluated. The median survival time was 7.6 months, and the 1-year survival rate was 25.0%. Grade 3/4 neutropenia occurred in 12 patients (30.0%), leukopenia in five patients (12.5%), and anemia in four patients (10.0%). The most common grade 3/4 nonhematologic toxicities were elevated ALT (15.0%) and elevated gamma-GTP (12.5%). One patient had grade 4 hemolytic uremic syndrome and recovered after discontinuation of gemcitabine. CONCLUSIONS: In single-agent therapy, gemcitabine demonstrated moderate efficacy with manageable toxicity in patients with advanced or metastatic biliary tract cancer. Further evaluations are warranted, including the exact impact of gemcitabine on the management of advanced or metastatic biliary tract cancer.
Noninvasive assessment of tumor vascularity by contrast-enhanced ultrasonography and the prognosis of patients with nonresectable pancreatic carcinoma.
BACKGROUND: Studies have shown that angiogenesis is one of the factors that influences the prognosis of patients with solid tumors, including pancreatic carcinomas. However, none have assessed noninvasively the relation between angiogenesis and prognosis in patients with pancreatic carcinoma. Contrast-enhanced ultrasonography (US) not only is a convenient, harmless, and noninvasive imaging modality, but it also provides detailed information on tumor vascularity. The objectives of this study were to assess the vascularity of pancreatic carcinoma noninvasively by contrast-enhanced US and to clarify the prognostic value of tumor vascularity in patients with nonresectable pancreatic carcinoma. METHODS: Thirty-five consecutive patients with pathologically confirmed, nonresectable pancreatic carcinoma were examined with contrast-enhanced US before systemic chemotherapy. The correlations among tumor vascularity, clinicopathologic factors, and clinical outcomes then were analyzed statistically to investigate prognostic indicators. RESULTS: The median time to progression (TTP) was longer in patients who had avascular tumors compared with patients who had vascular tumors (110 days vs. 28 days, respectively; P=0.0072; log-rank test). The median survival also was longer in patients who had avascular tumors (267 days vs. 115 days, respectively; P=0.0034; log-rank test). A multivariate analysis using a Cox proportional hazards model revealed that tumor vascularity was a significant, independent factor that influenced TTP (P <0.001) and survival (P=0.022) along with primary tumor size and serum lactate dehydrogenase (LDH) level, which are well known as prognostic factors in patients with pancreatic carcinoma. CONCLUSIONS: The current results indicated that contrast-enhanced US may be useful in assessing the prognosis of patients with nonresectable pancreatic carcinoma who receive systemic chemotherapy.
Ursodiol use is possibly associated with lower incidence of hepatocellular carcinoma in hepatitis C virus-associated liver cirrhosis.
In a previous study of patients with hepatitis C virus (HCV)-associated liver cirrhosis (HCV-LC), we showed that increased liver inflammation, as assessed by higher serum alanine aminotransferase (ALT), was associated with increased risk for the development of hepatocellular carcinoma (HCC). This suggested that suppression of inflammation might inhibit HCC development in HCV-LC. Several agents have been suggested to possess chemopreventive potential against the development of HCC in chronic HCV-associated liver disease, including herbal medicines, such as Stronger-Neo-Minophagen C (glycyrrhizin) and Sho-saiko-to (TJ-9). Ursodiol [ursodeoxycholic acid (UDCA)], a bile acid widely used to treat cholestatic liver diseases, also possesses anti-inflammatory properties in liver disease. We hypothesized that suppression of liver inflammation, as assessed by decreases in serum ALT, might inhibit HCC occurrence in patients with HCV-LC. In this study, the preventive effect of UDCA on HCC was examined in patients with early-stage HCV-LC. One hundred two patients with HCV-LC (Child stage A) were treated with anti-inflammatory drugs, Stronger-Neo-Minophagen C,Sho-saiko-to, or UDCA, with the goal of lowering the average serum ALT level to <80 IU. Iftheaverage ALT level did not remain <80 IU after treatment with one agent, multiagent therapy was initiated. The patients were followed up for >5 years and were retrospectively subdivided into two groups: 56 UDCA users (group A) and 46 UDCA nonusers (group B). The mean +/- SD dosage of UDCA administered in group A was 473.7 +/- 183.0 mg/d. The average duration of UDCA administration in group A was 37.3 +/- 15.9 months over the 5-year study period. The cumulative incidence of HCC was recorded. The 5-year incidence of HCC in group A was 17.9% (10 of 56) and was significantly lower than that in group B (39.1%, 18 of 46; P = 0.025). The risk for HCC incidence, calculated by a logistic regression model, showed that the administration of UDCA significantly decreased hepatocarcinogenesis (P = 0.036). The herbal medicines used were comparable in dosage and treatment duration in the UDCA and non-UDCA groups. In conclusion, UDCA might prevent HCC development in HCV-LC. Interestingly, because the serum ALT trends over time were nearly the same in both groups, the chemopreventive effectiveness of UDCA was not accompanied by greater reductions in ALT compared with the UDCA nonusers.
[Evaluation of biliary stenting therapy for malignant biliary stricture at our hospital].
The clinical results of biliary stenting therapy for non-resectable malignant biliary stricture were assessed for patency periods and survival periods in consideration of the types of stents and disease. The subjects were 51 patients with non-resectable malignant biliary stricture due to disease of the pancreas and biliary tract treated at our hospital between April 2001 and March 2005. No significant differences were observed in the patency periods and survival periods among the various types of stents. In regard to the type of disease, the survival period for biliary tract cancer was longer (616 +/- 246 days) than those for other diseases. There was no difference in the number of times of stenting among the various stents, and jaundice was effectively reduced. No patients in our series died of failure to reduce jaundice. We therefore considered it necessary to choose a proper stent indwelling route and a stent type according to stricture site, disease type and PS (performance status) at the time of stenting. The usefulness of the biliary stenting therapy for non-resectable malignant biliary stricture was suggested.
Sustained low alanine aminotransferase levels can predict the survival for 10 years without hepatocellular carcinoma development in patients with hepatitis C virus-associated liver cirrhosis of child stage A.
An analysis was performed of the patients with hepatitis C virus-associated liver cirrhosis (HCV-LC) who never developed hepatocellular carcinoma (HCC) for 10 years after the histological diagnosis of LC. Seventy-four consecutive HCV-LC patients of Child stage A were observed for >10 years prospectively for the development of HCC with frequent ultrasonography and magnetic resonance imaging or computed tomography. Of the 63 patients who fulfilled the study, 48 patients were treated and 15 were nontreated because of their stable state. They were subdivided into three groups according to their serum alanine aminotransferase (ALT) levels: the high ALT group comprised of 23 patients whose annual average serum ALT level was persistently high (>/=80 IU); the low ALT group comprised of 28 patients whose annual average serum ALT level was persistently low (<80 IU), and the unclassified ALT group comprised of 12 patients. In the low ALT group, as high as 71.4% of patients had never developed HCC for 10 years, in contrast to only 17.4% in the high ALT group (p < 0.001). In the 30 patients who never developed HCC for 10 years, 20 patients belonged to the low ALT group, in contrast to only 4 belonging to the high ALT group. Sustained low ALT levels were important to survive for 10 years without developing HCC in the HCV-LC patients of Child stage A.
Serum alanine aminotransferase levels and survival after hepatectomy in patients with hepatocellular carcinoma and hepatitis C virus-associated liver cirrhosis.
We examined whether sustained alleviation of inflammation as monitored by serum alanine aminotransferase (ALT) levels was associated with longer survival in hepatectomized hepatocellular carcinoma (HCC) patients with hepatitis C virus-associated liver cirrhosis (HCV-LC). Thirty-four hepatectomized patients with HCV-LC and HCC as a single nodule, and for whom more than 5 years had elapsed after the hepatectomy, were studied. They had no histologic evidence of portal or hepatic vein invasion. They were subdivided into two groups according to their serum ALT levels in the 2 years after hepatectomy: the low ALT group comprised 13 patients whose serum ALT levels showed a sustained low level below 80 IU, and the high ALT group comprised 21 patients whose serum ALT levels showed several peaks or plateaus above 80 IU. The patients had been followed-up prospectively with frequent ultrasonography and magnetic resonance imaging or computed tomography for recurrence for > 5 years. The survival period, non-recurrence interval and number of recurrences were observed. Recurrences were treated with transcatheter chemoembolization in all cases. The cumulative survival rate in the low ALT group was significantly better than that in the high ALT group (P < 0.05). The 5-year survival in the low ALT group was as high as 92.3% (12 of 13) compared with 33.3% (7 of 21) in the high ALT group (P < 0.05). The cumulative non-recurrence rate in the low ALT group was also significantly better than that in the high ALT group (P < 0.01). The survival period correlated well with the interval until the first recurrence (r = 0.545, P = 0.006). There was a tendency for the number of recurrences in the low ALT group (1.5 +/- 0.4, mean +/- SE) to be fewer than that in the high ALT group (2.2 +/- 0.4), although this was not significant. Sustained alleviation of inflammation, as indicated by low ALT levels, provides a survival advantage mainly due to the longer non-recurrence interval, and possibly because of fewer recurrences, in hepatectomized HCC patients with HCV-LC.
[A case of advanced pancreatic cancer showing remarkable response to gemcitabine treatment].
A 46-year-old woman with a 3-month history of upper abdominal pain was referred to our hospital because of the presence of a pancreatic mass and multiple hepatic nodules on abdominal ultrasonography (US) and computed tomography (CT). We concluded that the patient had pancreatic cancer with multiple hepatic metastases on the findings of endoscopic retrograde cholangiopancreatography (ERCP) and fine needle aspiration biopsy of the hepatic nodule. The patient received gemcitabine treatment. Gemcitabine 1,000 mg/m2 was administered once a week for 3 weeks followed by a week of rest, this constituting 1 cycle of treatment. Partial responses (PR) of both pancreatic and hepatic lesions were observed after the first cycle of the gemcitabine treatment, and serum concentrations of CEA and CA19-9 remarkably decreased. We considered that clinical benefit was obtained because Karnofsky performance status improved and analgesic consumption decreased. Such effectiveness of the gemcitabine treatment lasted for the following 4 cycles. In general, chemotherapy has few effects on an advanced pancreatic cancer. We report a case of advanced pancreatic cancer that could obtain remarkable antineoplastic effect and clinical benefit with gemcitabine treatment.
Close association between high serum alanine aminotransferase levels and multicentric hepatocarcinogenesis in patients with hepatitis C virus-associated cirrhosis.
BACKGROUND: Multicentric development of hepatocellular carcinoma (HCC) is a characteristic feature of hepatitis C virus (HCV)-associated cirrhosis (HCV-LC). In this study, the objective was to determine whether the persistent elevation of the serum alanine aminotransferase (ALT) level, which represents the inflammatory necrosis of hepatocytes, is correlated with the multicentric development of hepatocellular carcinoma (HCC) in patients with early-stage HCV-LC. METHODS: Ninety-three consecutive patients with biopsy proven HCV-LC (Child Stage A) who had been followed for > 5 years for the development of HCC were studied. They were subdivided into three groups according to their serum ALT level: Group A included 33 patients with annual average serum ALT levels that were persistently high (> or = 80 IU; high ALT group), Group B included 41 patients with annual average serum ALT levels that were persistently low (< 80 IU; low ALT group), and Group C included 19 unclassified patients. The patients had been studied prospectively with frequent ultrasonography and magnetic resonance imaging or computed tomography (CT) scans for > 5 years. When the development of HCC was suspected, angiography, infusion of lipiodol into the hepatic artery, and lipiodol-CT scans were performed in all patients to determine the number of HCC nodules. RESULTS: In Group A, 27 patients (81.8%) developed HCC. Seventeen of 27 patients (63.0%) had multiple nodules. In contrast, in Group B, only 12 patients (29.3%) developed HCC, and only 1 of these 12 patients (8.3%) had multiple nodules. There was a significant difference between Groups A and B in the incidence of developing HCC (P < 0.001) and developing multiple nodules (P = 0.006). In addition, among the male patients, the incidence of developing multiple HCC nodules in Group A (12 of 19 patients; 63.2%) was significantly higher (P < 0.05) compared with the incidence in Group B (0 of 6 patients; 0%). The same tendency was observed among the female patients. CONCLUSIONS: These results showed a close correlation between multicentric hepatocarcinogenesis and sustained necroinflammation of the liver in patients with HCV-LC.
[Examination of percutaneous microwave coagulation and radiofrequency ablation therapy for metastatic liver cancer].
Percutaneous microwave coagulation therapy (PMCT) and radio frequency ablation therapy (RFA) as treatments for metastatic liver cancer were examined. PMCT or RFA was administered for 18 metastatic liver cancer lesions (primary lesion: 11 colon rectal cancer, one esophagus cancer, one thyroid cancer, one pancreatic cancer, one pheochromocytoma) in 16 patients from July 1999 to March 2002. RFA was performed 1 time for 12 minutes in principle, using a Cool-tip RF system from Radionics. Patients had a mean age of 58.8 years and the mean diameter of the neoplasms was about 22 mm. Critical complications were not seen. The rate of partial recurrence was 35.3% as of March, 2002, in an average observation period of 7.3 months. On the other hand, with the medical treatment for the hepatocellular carcinoma provided during this period, the rate of partial recurrence was 14.8%. The treatment of metastatic liver cancer by PMCT and RFA is associated with a high rate of a recurrence as compared with hepatocellular carcinoma, and needs to be examined to discover ways of adaptation and improvement of the technology.
Reduction therapy of alanine aminotransferase levels prevent HCC development in patients with HCV-associated cirrhosis.
BACKGROUND: To find a way to prevent the development of hepatocellular carcinoma (HCC) from hepatitis C virus-associated liver cirrhosis (HCV-LC), an analysis of the HCV-LC patients who had received reduction therapy of the alanine aminotransferase (ALT) levels was performed. PATIENTS AND METHODS: Seventy-four consecutive HCV-LC patients of Child Stage A were followed for >10 years for the development of HCC. They were divided into two groups: in group A, the reduction therapy for the ALT levels was aggressively performed, while in group B, the reduction therapy was not performed aggressively. The patients were subdivided into three sub-groups according to their serum ALT levels. In groups A and B, the high ALT group was comprised, respectively, of nine and five patients whose annual average serum ALT levels were persistently high (> or =80 IU), while the low ALT group was comprised of 19 and 20 patients whose annual average serum ALT levels were persistently low (<80 IU). The remaining eleven and ten patients had annual average serum ALT levels which fluctuated and were unclassified (unclassified group). RESULTS: In group B, 65.7% of the patients had developed HCC in 13 years, in contrast to only 41.0% of group A (p=0.039). In group A, the median HCC development time was 12.8 years, in contrast to only 3.8 years in group B (p=0.0013). Multivariate analysis demonstrated that the mode of reduction therapy and ALT levels were the significant factors affecting HCC development. CONCLUSION: The chances of surviving for more than ten years without developing HCC for HCV-LC patients