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Biomedical subjects

Hiroshi Imamura

Publications and source records attributed to Hiroshi Imamura.

At least 19 recordsLinked to original sources

Phase II study of protracted irinotecan infusion and a low-dose cisplatin for metastatic gastric cancer.

AIM: To test protracted irinotecan infusion plus a low-dose cisplatin in this Phase II trial to decrease its toxicity. METHODS: The eligibility criteria were: (1) histologically proven measurable gastric cancer; (2) performance status of 0 or 1; (3) no prior chemotherapy or completion of prior therapy at least 4 wk before enrollment; (4) adequate function of major organs; (5) no other active malignancy; and (6) written informed consent. The regimen consisted of irinotecan (60 mg/m(2)) on d 1 and 15 by 24-h infusion and cisplatin (10 mg/m(2)) on d 1, 2, 3, 15, 16, and 17. Treatment was repeated every 4 wk. RESULTS: Thirty-one patients were registered between April 2000 and January 2001. The response rate for all 31 patients, 20 patients without prior chemotherapy, and 11 patients with prior chemotherapy was 52% (16/31), 60% (12/20), and 36% (4/11), respectively. The median survival time was 378 d. The median number of courses given to all patients was 2. Grade 4 neutropenia occurred in 11 (35%) patients, while grade 3 to 4 diarrhea or nausea occurred in 1 (3%) and 3 (10%) patients, respectively. Fatigue was minimal as grade 1 fatigue was found only in 3 (10%) patients. Other adverse events were mild and no treatment-related deaths occurred. CONCLUSION: This regimen showed a high level of activity and acceptable toxicity in patients with metastatic gastric cancer.

Adult↗

Liver transplantation using donors with Gilbert syndrome.

Serum bilirubin level is an essential factor included in the first step in evaluating living liver donor candidates. Our evaluation strategy was examined in living donors with possible Gilbert's syndrome (GS). When donor candidates had hyperbilirubinemia (>1.5 mg/dl), but otherwise normal liver function tests, their genomic DNA was isolated from leukocytes. They were diagnosed with GS when they had mutations of uridine diphosphate glucuronosyltransferase 1 typical to GS. The donors and recipients were divided into two groups: GS donors and their recipients (n = 6, each) and non-GS donors and their recipients (n = 65). All GS donors and their recipients had an unremarkable postoperative course. Total bilirubin levels of the recipients of GS donors were higher than those of recipients of non-GS donors. Living donor liver transplantation is safe for both donors with GS and their recipients.

Bilirubin↗

Mechanisms of atrial tachyarrhythmia induction in a canine model of autonomic tone fluctuation.

BACKGROUND: The purpose of this study was to investigate the effect of cholinergic modulation in the presence of increased adrenergic tone (i. e., autonomic fluctuation) on atrial tachyarrhythmia (AT) induction. METHODS AND RESULTS: High-resolution optical mapping was used to measure action potentials from the left atrium in isolated arterially perfused canine atrial preparations. Optical recordings were made in the presence of isoproterenol during electrical stimulation of a fat pad at the right pulmonary veinatrial junction (Group I, n = 6), during electrical stimulation of a fat pad locating the superior vena cava contacted by the right pulmonary artery (Group II, n = 4), and during acetylcholine (ACh; Group III, n = 4) infusion. In the presence of isoproterenol,each of the three different transitory cholinergic interventions induced spontaneous AT in all preparations. In Group I, AT induced from the right atrium was sustained. However, AT induced from the left atrium was not sustained (RRB) in Group I. In Groups II and III, AT induced from the left atrium as well as the right atrium were also sustained (BAF-AT). The A1A2 coupling interval was shorter when BAF-AT was induced than it was when RRB was induced. Mean cycle length of repetitive focal excitation was shorter during the initiation of BAF-AT compared to RRB. Isochrone maps during the initiation of AT demonstrated a macroreentry with lines of conduction block following a single extrasystole (27 %) and focal repetitive excitation (73 %). CONCLUSIONS: These results suggest that transitory cholinergic activation in the presence of increased adrenergic drive in the left atrium causes a single premature extrasystole with a short coupling interval and a focal repetitive excitation with a short cycle length, which favors the generation of AT originating from the left atrium.

Adrenergic Fibers↗

Expression of transforming growth factor-alpha and -beta in hepatic lobes after hemihepatic portal vein embolization.

Hemihepatic portal vein embolization (PVE) concomitantly induces atrophy in embolized and compensatory hypertrophy in nonembolized hepatic lobes. The aim of the present study was to evaluate the involvement of growth stimulatory and inhibitory factors in these hepatic lobes after PVE. Liver specimens from the embolized and nonembolized lobes of ten patients who underwent hepatectomy (8-22 days) after undergoing PVE were obtained. Proliferation and apoptosis were examined immunohistochemically using Ki-67 and the Tdt-mediated dUTP-biotin nick end-labeling method. The expression of transforming growth factor-alpha (TGF-alpha) and transforming growth factor-beta (TGF-beta) was also examined by immunohistochemical staining. PVE induced hepatocyte apoptosis in the embolized lobe and hepatocyte proliferation in the nonembolized lobe. TGF-alpha expression in the hepatocytes of the nonembolized lobe was markedly increased, whereas TGF-alpha was also overexpressed, albeit moderately, in the embolized lobe. In contrast, TGF-beta expression in the hepatocytes of the embolized lobe was significantly increased, and TGF-beta expression was also increased, although to a lesser extent, in the nonembolized lobe. The degree of volume changes of the nonembolized lobe and the embolized lobe after PVE was statistically correlated with the ratios of TGF-alpha and TGF-beta expression in these lobes (r = 0.886, P < .0001). In conclusion, these findings indicate that TGF-alpha and TGF-beta expression (assessed by immunohistochemical staining) increase in relation to hepatocyte proliferation and apoptosis, respectively, after PVE in humans and the balance of the two factors may contribute to hepatic atrophy and hypertrophy concomitantly observed in this model.

Aged↗

Morphological regeneration and hepatic functional mass after right hemihepatectomy.

BACKGROUND/AIMS: Liver has a remarkable ability to regenerate after major resection. However, little is known about the process of morphological regeneration and hepatic functional recovery in human. METHODS: Sixteen donors who underwent right hemihepatectomy were enrolled in this prospective clinical study. The preoperative liver volume and remnant liver volume on postoperative days 5, 12 and 28 were calculated from serial transverse computed tomography images. Liver function was evaluated by measuring the intrinsic clearance of antipyrine before and on postoperative days 5 and 12 days, as well as the biochemical and coagulation assay. RESULTS: A smaller residual liver tended to regenerate faster in 28 days. Operative factors, including intraoperative blood loss, inflow occlusion time, liver transection time and duration of operation were not significantly correlated with postoperative liver regeneration. The intrinsic clearances of antipyrine on postoperative days 5 and 12 days were significantly reduced compared to the respective values before the operation (p < 0.001 and p < 0.05, respectively). On the contrary, the intrinsic clearance values per unit liver volume significantly increased on postoperative 12 days (p < 0.05). CONCLUSION: The microsomal function of individual hepatocytes may be upregulated after right liver resection perhaps in order to compensate for the reduced functional mass of the liver.

Adolescent↗

Pancreaticoduodenectomy after esophageal and gastric surgery preserving right gastroepiploic vessels.

Secondary pancreaticoduodenectomy was performed in 2 patients, 1 who had undergone proximal gastrectomy for a gastric carcinoma and 1 who had undergone subtotal esophagectomy with stomach tube reconstruction for an inferior thoracic esophageal carcinoma. To prevent ischemia and congestion of the remnant stomach, the inflow and outflow pathways to the stomach, such as the right gastroepiploic artery and vein, were preserved. In this article, we describe the preservation procedures and discuss the problems of the secondary abdominal surgical procedure.

Carcinoma↗

Uracil-tegafur as an adjuvant for hepatocellular carcinoma: a randomized trial.

Frequent recurrence of hepatocellular carcinoma (HCC) after surgery remains a major clinical problem. This randomized controlled trial evaluated whether postoperative adjuvant therapy with oral uracil-tegafur (UFT) prevents recurrence of HCC. A total of 160 patients who underwent curative hepatic resection for HCC were randomly assigned to receive either 300 mg/day of UFT for 1 year after surgery (n = 79, UFT group) or surgery alone (n = 80, control group). The primary endpoint was recurrence-free survival, and the secondary endpoint was overall survival. Other study variables included liver function and type of recurrence. During a median follow-up of 4.8 years (range: 0.5-7.9), recurrence-free survival curves in the groups were similar (P = .87). Overall survival was slightly but not significantly worse in the UFT group than in the control group (P = .08). The rates of recurrence-free and overall survival at 5 years were 29% and 58%, respectively, in the UFT group, as compared with 29% and 73%, respectively, in the control group. The hazard ratio for recurrence in the UFT group, relative to the control, was 1.01 (95% confidence interval: 0.84-1.22, P = .87). The proportion of patients with advanced recurrence (i.e., multiple, extrahepatic, or associated with vascular invasion) was significantly higher in the UFT group (74%, 43 of 58 patients with recurrence) than in the control group (53%, 30 of 57) (P = .02). In conclusion, our results offer no evidence to support potential benefits of adjuvant chemotherapy with UFT after surgery in patients with HCC and suggest that such treatment may even worsen overall survival.

Adult↗

Portal vein reconstruction in adult living donor liver transplantation using cryopreserved vein grafts.

No data are available for the management of venous jump or interposition conduits for portal vein (PV) reconstruction in adult living donor liver transplantation (LDLT). The feasibility of using cryopreserved vein grafts as PV conduits was examined. Cryopreserved vein (n = 23) was used as a patch, interposition, or jump graft. The patency results were compared with those of anastomosis without vein patch (n = 217) or those with vein autografts (n = 10). The 5-yr primary and secondary patency rates of the cryopreserved vein grafts were 58% and 79%, respectively. In conclusion, our data indicate that the use of cryopreserved vein grafts should be limited as conduits in PV reconstruction in adult LDLT.

Adult↗

Temporary inferior vena cava filter for deep vein thrombosis and acute pulmonary thromboembolism: effectiveness and indication.

Although the temporary inferior vena cava filter (IVC-F) is being used increasingly for protection against pulmonary thromboembolism (PTE), indications for its use are not established. Our strategy for the prevention of PTE is: (1) contraindication or failure of anticoagulation: permanent IVC-F; (2) for patients with residual proximal deep vein thrombosis (a) who have permanent risk factor: permanent IVC-F; (b) who have transient risk factor: temporary IVC-F; (3) others: no IVC-F. Temporary IVC-F was also implanted in deep vein thrombosis (DVT) patients without PTE who were preoperation or had floating thrombus. We investigated the outcome of patients given a temporary IVC-F versus those given a permanent IVC-F to clarify the efficacy and our strategy for implantation of a temporary IVC-F. Subjects were 12 men and 38 women with acute PTE and/or floating DVT admitted to our hospital between April 1999 and April 2002. Patient age was 25-91 years (mean 63 years). Eighteen patients were given a permanent IVC-F (group A) and 32 patients were given a temporary IVC-F (group B) as primary treatment, according to our criteria. There were no major complications in either group. Mortality after implantation of the IVC-F was 35% (6/17) in group A and 16% (4/25) in group B, with no significant difference (P = 0.14). Pulmonary thromboembolism recurred in 18% (3/17) of group A patients but in no group B patients (P = 0.10). All recurrences resulted in death. The 14 patients in group B who were not given a permanent IVC-F after removal of the temporary IVC-F survived. The temporary IVC-F can be used safely in patients with venous thromboembolism and is efficacious in preventing recurrence of PTE. Prognosis after removal of the temporary IVC-F is excellent.

Aged↗

Simultaneous resection of liver cell adenomas and an intrahepatic portosystemic venous shunt with elevation of serum PIVKA-II level.

A 27-year-old woman with no history of liver disease or oral contraceptive use presented with sudden abdominal pain. Laboratory data showed mild liver dysfunction with jaundice. Computed tomography and angiography revealed centrally located large liver cell adenomas (LCAs) and an intrahepatic portosystemic venous shunt (IHPSS) in the left lobe. The serum des-gamma-carboxy prothrombin (known as "protein induced by a lack of vitamin K or antagonist II," PIVKA-II) level was extremely high (6,647 mAU/ml), indicating malignant transformation of the tumors. Under the diagnosis of LCAs and IHPSS, the patient underwent simultaneous resection of the four liver tumors and portovenous shunt, and the hepatic vascular abnormality was resolved. The pathological diagnosis was LCAs without hepatocellular carcinoma. Immunohistochemical analysis with an anti-PIVKA-II monoclonal antibody showed positive staining of the adenoma cells. This case shows that LCA without malignant transformation can produce PIVKA-II, leading to high serum levels of PIVKA-II. Simultaneous resection of multiple tumors and closure of the portosystemic shunt are strongly recommended in a patient with LCA associated with IHPSS.

Adenoma, Liver Cell↗

Multicenter phase II study of antimicrobial prophylaxis in low-risk patients undergoing distal gastrectomy for gastric cancer.

BACKGROUND: In Japan, antimicrobial prophylaxis (AMP) is typically administered for 3 to 4 days postoperatively for clean-contaminated operations such as distal gastrectomy. This far exceeds the recommended 2h or less laid out by the Centers for Disease Control (CDC) guidelines for the prevention of surgical-site infections (SSIs), after a clean-contaminated operation. METHODS: Patients with gastric cancer, which was curable by distal gastrectomy with D2 lymphandectomy, were assigned to a multicenter phase II study. One gram of cefazolin within 3 min of the first surgical incision and intraoperative supplements of g of cefazolin every h were administered. AMP was not administered after skin closure unless postoperative infection occurred. The occurrence of SSIs was monitored until postoperative day 30 as the primary endpoint of this study. RESULTS: In 56 patients, three SSIs (5.4%) and one remote site infection (1.8%) developed. No other postoperative infections were observed. CONCLUSION: Our data indicate that the CDC guidelines regarding AMP may also be sufficient for patients undergoing clean-contaminated operations in Japan.

Anti-Bacterial Agents↗

Regeneration and function of hemiliver graft: right versus left.

BACKGROUND: A right liver graft used almost routinely for adult living donor liver transplantation (LDLT), is associated with a higher incidence of morbidity and mortality in the donor. We compared volume regeneration and graft function between left and right liver grafts to examine the feasibility of using left liver grafts. METHODS: The left liver was considered acceptable as a graft when it was estimated to be over 40% of the recipient standard liver volume. Otherwise, right liver harvesting was used, provided the estimated right liver volume was less than 70% of the donor's standard liver volume. Graft volume on computed tomography and the results of liver function tests 1, 3, and 12 months after LDLT were compared between recipients with left (n = 76) and right (n = 83) grafts. Possible factors influencing graft regeneration were evaluated by multivariate analysis. RESULTS: A higher regeneration rate in the left liver graft group resulted in the same ratio of graft to standard liver volume as in the right liver graft group (88% vs 87%) 1 year after LDLT. Liver function tests and 5-year survival rates were comparable between the 2 groups. An episode of acute rejection was a predictive factor for impaired graft regeneration 1 month after LDLT. The initial ratio of graft volume to standard liver volume was an independent factor for regeneration 1 year after LDLT. CONCLUSIONS: A properly evaluated left liver graft can be used as safely as a right liver graft in adult-to-adult LDLT. The findings of the present study justify LDLT with a left liver graft under specific selection criteria and may be preferred to a right liver graft.

Adult↗

Characteristics of metabolic and lifestyle risk factors in young Japanese patients with coronary heart disease: a comparison with older patients.

Coronary heart disease (CHD) is recognized as a lifestyle-related disease and is the second leading cause of death in Japan. However, the cardiac risk factor profile of young patients with CHD has not been clarified in suburban areas of Japan. Our study aimed to determine metabolic and lifestyle risk factors in young patients and compare them with older patients living in suburban areas of Nagano Prefecture. A multicenter study was conducted in 86 young (aged less than 40 years) and 91 older (aged 50 years and over) patients diagnosed with CHD from 1992 to 2002. There was a strong association between obesity and the occurrence of CHD events in young patients (odds ratio = 3.61, P = 0.006). Lifestyle in the young patients was characterized by a lack of physical activity and regular physical activity was found to decrease the risk of the CHD events in these patients (odds ratio = 0.31, P = 0.030). In older patients, hypertension was identified as an independent risk factor for CHD events. The results of the present study have demonstrated that obesity and a lack of regular physical exercise are independent risk factors for CHD events in younger patients. Thus, the data may be useful for the effective screening of high-risk individuals and the development of educational programs for the prevention of CHD, especially in younger Japanese.

Adult↗

[Visceral hypersensitivity].

Colorectal hyperalgesia has been supposed to be one of the key pathophysiological roles in irritable bowel syndrome (IBS). Recent animal models have demonstrated that neonatal maternal deprivation (stress memory) or repetitive rectal distension (pain memory) in neonatal animal triggers long-term hypersensitivity to rectal distension, indicating that negative events including abuse or maternal separation in childhood may play a crucial role on development of IBS. Several molecules such as corticotropin-releasing factor, serotonin, nerve growth factor, myosin light chain kinase, chemical mediators from mast cell, substance P and calcitonin gene-related peptide released from transient receptor potential vanilloid receptor 1 (TRPV1)-positive primary afferent nerves have been proved to induce visceral hyperalgesia. Novel drugs based on these findings have been developed.

Animals↗

[Neoadjuvant therapy with imatinib mesilate for gastrointestinal stromal tumor of the stomach before subsequent successful surgical resection].

A 65-year-old man is presented here with a huge mass of 13 cm in diameter in the left upper abdomen. Histopathologic assessment of endoscopic forceps biopsy revealed a c-kit positive gastrointestinal storomal tumor (GIST) of the stomach. Abdominal computed tomography (CT) showed a direct invasion to the pancreas. Imatinib mesilate was administered as neoadjuvant therapy according to the NCCN Guidelines. Imatinib mesilate therapy was stopped within 2 weeks because of adverse events such as Grade 2 of facial edema and dizziness. However, no hematological adverse event was shown. After three months of treatment (relative dose intensity was 87.5%), CT revealed a reduction in tumor diameter of 35.6% and showed no longer a direct invasion to the pancreas. The radical operation was considered feasible and partial gastrectomy was performed. The tumor was well encapsulated and radical surgery was possible without rupture. Adjuvant therapy was not performed. The patient has now been in good health without a recurrence for three months after the surgery.

Aged↗

[A case of an elderly patient with gastric cancer successfully treated with TS-1 considering impaired renal function caused by aging].

A 75-year-old female patient with impaired renal function caused by aging was treated with TS 1 for gastric cancer with extensive multiple liver metastases. TS-1 contains CDHP, which inhibits DPD activity and maintains a high blood concentration of 5-FU. Because CDHP is excreted from the kidney, a careful TS-1 administration is necessary for patients with impaired renal function considering an occurrence of severe adverse events. Based on the result previously reported by us about pharmacokinetic study and recommended administration dosage of TS-1 for patients with impaired renal function, we administered 50 mg/day of TS-1 for four weeks followed by two weeks rest per one course for this patient. The patient's creatinine clearance calculated by the Cockcroft-Gault method was 38 ml/min, and we reduced the administration dosage in consideration of her impaired renal function, although normal dosage of TS-1 calculated from body surface area for this patient was 100 mg/day. As this patient underwent TS-1 treatment, sizes of multiple liver metastases and the blood concentration level of CEA were gradually reduced, and the reductive rate of the former was more than 90% and the level of the latter fell to a normal range after 12 courses of TS 1 treatment. Through all the treatment courses, relative drug intensity was 100% and the performance status of this patient was kept 0 without any grade 3 or more adverse events under ambulatory treatment. A successful treatment for this patient might indicate that it was important to consider the appropriate reduction of the dosage of TS-1 administration for elderly patients with gastric cancer, because there is a reverse correlation between aging and renal function. To clarify this problem, a multicenter prospective phase II study about TS-1 reductive administration depending on the renal function for elderly patients with gastric cancer (OGSG0404) is ongoing in our clinical study group (OGSG; Osaka Gastrointestinal Chemotherapy Study Group).

Aged↗

[A case of complete remission of carcinomatous ascites refractory for TS-1 monotherapy treated with TS-1 plus paclitaxel combined therapy for gastric cancer].

A 38-year-old female patient with gastric cancer, of which histological type was a poorly differenciated adenocarcinoma and a clinical finding was T3N1MO (Stage IIIA), underwent total gastrectomy with D2 lymphadenectomy as the surgical treatment. However, CY1 was detected during the operation and the final finding was T3N1MOHOPOCY1 (Stage IV). Because this surgical treatment ended in curative C, we administered 80 mg/m2/day of TS-1 for four weeks followed by two weeks rest per one course for CY1 after the surgical treatment. After two courses of TS-1 monotherapy, extensive carcinomatous ascites appeared and blood concentration level of CA19-9 increased. We next treated this patient with TS-1+paclitaxel as a second line chemotherapy, because both of them have been reported to migrate to peritoneal very well and to be effective for peritoneal dissemination. The regimen of this combined therapy consisted of four weeks administration of TS-1 (80 mg/m2/day) followed by two weeks rest and injections of paclitaxel (50 mg/m2) at day 1 and 8 for 21 days as one course. When this patient underwent TS-1+paclitaxel combined treatment, the amount of carcinomatous ascites and blood concentration level of CA19-9 were gradually reduced and the former completely disappeared, and the latter fell to a normal range after five courses. Through all treatment courses, a performance status of this patient was kept 0 without a severe adverse event under ambulatory treatment. After 29 courses, the blood concentration level of CA19-9 rose again and local recurrence was detected at the lesion of esophagoenterostomy, though carcinomatous ascites had been kept in complete remission. We treated surgically for this local recurrence because of CY0 at the operation. At the present, 3 years and 8 months have passed since the first treatment started. This patient is still alive without cancer in ambulatory.

Adenocarcinoma↗