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Biomedical subjects

Masaki Kitajima

Publications and source records attributed to Masaki Kitajima.

At least 217 records · Page 12Linked to original sources
PubMed2002

[Intra-arterial infusion chemotherapy for breast cancer].

Intra-arterial infusion chemotherapy has a significant effect in down-staging locally advanced breast cancer by providing a high dose intensity. It is also used for the treatment of liver metastasis. A better response rate and lower incidence of adverse effects are reported when patients are treated with intra-arterial infusion chemotherapy than with systemic chemotherapy using the same dose of the same drugs. Recent advances in devices such as access ports and portable infusion pumps make it possible to perform intra-arterial infusion chemotherapy repeatedly and safely. However, it remains uncertain whether or not intra-arterial infusion chemotherapy can improve the prognosis of cancer patients because of the lack of data from phase III trials. Accordingly, further studies including combined use of systemic chemotherapy are mandatory to the control of micrometastases outside the target organ.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

[State of the art and problems in medical safety management].

The principle of medical safety management is to build a safe medical system that is equipped to prevent patient injuries due to medical errors occurring in it and not to attribute them only to individual responsibility. Methodologically, this means identifying and reducing the potential risk of medical errors by systematic reporting and tracking of errors and near misses. According to some major clinical studies on medical malpractice in the USA, the incidence of medical accidents is reported to be 3-5%, 30% of which were due to negligence, and 7-14% resulted in patients' deaths. It is also reported that 66% of the medical accidents occurred in surgical specialties and 45% were related to surgeries, which were shown to have the highest risk of medical accidents. On the other hand, according to a nationwide survey on reported errors and near misses in Japan, 50% were related to drugs, especially injections. Other major causes reported in the study were manipulation and management of medical instruments, downfalls of patients, and aspiration. These safety problems listed above were shown to compose 95% of all of medical errors and near misses. To establish a rational safety management system, it is necessary to develop research methods appropriate for the study of medical errors, which facilitate clinical research, and can be expected to yield sufficient scientific data. A generalized guideline for voluntary reporting of patients' deaths and injuries due to medical errors, in relation to Article 21 of the Doctors' Law should be established. However, for essential improvement of transparency and accountability in medicine, it is necessary to set up a new specialized institute to accept reports on medical errors, give hospitals advice for a safer medical system, and disclose information on medical errors. Moreover, such an institute should continue to study medical safety by analyzing nationwide reports of medical errors and near misses. For the latter purpose, legal protection of the disclosure of information must be assured.

General Surgery↗
PubMed2002

[Molecular alterations in esophageal cancer].

The clinicopathological characteristics of esophageal cancer have gradually been clarified using molecular biologic methods developed over the past 20 years. For example, amplification of the c-erb B gene is a prognostic factor and predictive of lymph node involvement, while the amplification of the cyclin D1 gene is also a prognostic factor and predictive of distant organ metastasis. Alteration of the p16 gene is also a prognostic factor and predicts lymph node involvement. As telomerase activity is almost a unique phenomenon of cancer cells, highly sensitive detection of esophageal cancer cells in the peripheral blood can be performed. Recently, such new methods as comparative genomic hybridization analysis and cDNA microarray analysis have been used to determine meaningful genetic changes. For therapeutic purposes, although tailor-made therapy has been proposed for several years, the validity of these approaches should be confirmed in a well-designed clinical trial. As molecular targeted therapies, tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR) and monoclonal antibodies against EGFR are being studied in clinical trials in Western countries. A clinical trial of p53 gene therapy against esophageal cancer is also promising.

Cyclin D1↗
PubMed2002

[Developments in endocrine therapy for breast cancer].

After the usefulness of ovariectomy in breast cancer patients was demonstrated, endocrine therapy has been one of the most effective treatments of breast cancer. Thereafter, it became clear that estrogen receptors (ERs) existed in the cells of breast cancer. After it was found that ERs could be used as a predictive factor of endocrine therapy for breast cancer, the validity of endocrine therapy has became more certain. Tamoxifen, a major selective estrogen receptor modulator, is the first agent which has shown evidence of improving survival time and disease-free survival time in the treatment of breast cancer, and is the standard treatment, widely used in the treatment of breast cancer all over the world. LH-RH analogue, commonly used in ablation treatment among premenopausal women, produces the same effect as ovariectomy, and recently has shown good results equivalent to chemotherapy in premenopausal breast cancer treatment. Furthermore, aromatase inhibitors as a form of ablation treatment of postmenopausal women have been used recently. In comparison with tamoxifen, aromatase inhibitors have revealed the same or more effective result in postmenopausal breast cancer treatment. In the near future, endocrine mechanisms in the body and the molecular mechanisms of transcription by ER will be more clearly elucidated, and then new kinds of agent and combined therapies for the endocrine treatment of breast cancer will be developed. Currently, many clinical randomized trials are being conducted to examine the effectiveness of new endocrine treatment. Significant changes are occurring in the endocrine treatment of breast cancer.

Antineoplastic Agents, Hormonal↗
PubMed2002

[Early phase II dose-finding study of exemestane in postmenopausal patients with advanced/recurrent breast cancer].

Exemestane was administered orally to postmenopausal women with advanced/recurrent breast cancer at a dose of 10 mg/day or 25 mg/day once daily for more than 8 weeks in order to evaluate the drug's anti-tumor effects and safety in a dose-finding study. The response rate (CR + PR) in the 10 mg and 25 mg group was 25.0% (8/32) and 31.4% (11/35), respectively, demonstrating no significant differences between the two groups, yet a higher efficacy rate was observed in 25 mg group. The efficacy rate in hormone-treatment-resistant patients within the 10 mg and 25 mg groups was 14.3% (3/21) and 26.1% (6/23), respectively, demonstrating more than a 20% response rate in 25 mg group. Incidences of the adverse events of which relevance to the drug could not be excluded were 30.6% (11/36) in the 10 mg group. 13.9% (5/36) in the 25 mg group and 22.2% (16/72) in the total group. The major adverse events were, hot flashes, numbness of the limbs, nausea, headache etc. Abnormal findings in clinical laboratory tests were as follows: ALP increase; GOT increase; GPT increase; gamma-GTP increase; total cholesterol increase; urinary sediment present. Abnormal findings in endocrine function were as follows: aldosterone decrease; testosterone.cortisol.DHEA-S decrease. But discontinuation due to abnormal laboratory findings was not found. No abnormal findings in physical tests were observed. A significant decrease in plasma estrogen concentration at week 4 was observed in both the 10 mg and 25 mg groups compared with baseline. These low levels were maintained throughout the study period. On the basis of these results, the efficacy of exemestane 25 mg/day was verified to be slightly higher than 10 mg/day. In addition the safety profile had no major adverse events to notice. In these patients with advanced/recurrent breast cancer, 25 mg/day was recommended as the most appropriate dose to be used clinically.

Administration, Oral↗
PubMed2002

[A novel combined chemotherapy using TS-1 and low-dose cisplatin against liver metastasis of gastric cancer].

We used a novel combination chemotherapy of TS-1 and low-dose cisplatin (CDDP) with 4 gastric cancer patients with liver metastases (one far advanced and 3 recurrent patients). TS-1 was administered at 80 mg-120 mg/body/day, twice daily for 3 weeks followed by a 2-week interval as one cycle, and CDDP was administered at 6 mg/m2/day div, for 5 days followed by a 2-day interval (1 cycle for an inpatient) or at 6 mg/m2/day div, at 5 times for 2-3 weeks (1 cycle for an outpatient). Efficacy and toxicity were evaluated after 3-6 cycles of the regimen, as long as the patients tolerated the regimen without severe side effects. This regimen resulted in 1 complete response, 2 partial responses and 1 progressive disease, showing a 75% efficacy rate. One patient experienced grade 2 nausea from this regimen, which was ameliorated by means of prolonging the interval of CDDP-administration. Thus, the regimen is useful to maintain patients' quality of life without severe adverse effects, and has a high efficacy in gastric cancer patients with liver metastases.

Administration, Oral↗
PubMed2002

[Breast cancer].

Adjuvant chemo-endocrine therapy for breast cancer (ACETBC) trial has been the first large scaled clinical trial performed in Japan. Several prospective randomized trials have been performed in Japan since ACETBC-1 trial started in 1985. The effect of oral 5-FU agents had been tested in prospective randomized trials and the statistically marginal effect of oral 5-FU agents in adjuvant settings has been reported. Several trials having CMF as a control arm started in 1996 when CMF combination chemotherapy was approved by the government. The results of these trials have not been published. To perform good clinical trials, it is imperative to construct infrastructures including clinical research coordinator, and abolish governmental regulation of the dose of anticancer agents.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

[Endoscopic surgery in children: current status and problems].

Endoscopic surgery has been established in various surgical conditions in children and infants for the past 10 years after pioneering work by experts specializing in pediatric endosurgery. These include pull-through for Hirschsprung's disease and anorectal malformations, pyloromyotomy, hernia repair, and endoscopic surgery for malignancies, malrotation, intussusception, etc. Laparoscopic pull-through is now accepted as a standard modality for the treatment of Hirschsprung's disease. Advanced endoscopic procedures such as esophageal atresia repair or fetal tracheal occlusion have also been performed. An efficient system for training is needed to compensate for the small number of patients and varieties of specific illness in children.

Child↗
PubMed2002

[Intensive therapy for fulminant hepatic failure: importance of co-operation between physicians of internal medicine and transplantation surgery].

We followed up the patients with fulminant hepatic failure who admitted in our hospital and investigated clinical problems raised in the patients who underwent living-related liver transplantation (LRLT). Among 15 patients with fulminant hepatic failure 6 were managed without LRLT and 3 patients survived, and the survival rate was 50%. Other 9 patients received LRLT, and 2 of these 9 died with their complications after the transplantation. Thus the survival rate by LRLT in fulminant hepatic failure was 77.8%. Brain CT scan examination showed severe brain edema in a patient and the edema did not improve after LRLT. Another patient suffered from development of fungal infection in her lungs after LRLT. We suspected the presence of subclinical infection in the preoperation period. The recovery from brain edema and the existence of subclinical infection are mostly difficult to evaluate but are very important for obtaining a good output. These results suggest that LRLT is a promising procedure for treatment of fulminant hepatic failure but a close cooperation between physicians of internal medicine and transplantation surgery from preoperative management until postoperative period is necessary.

Acute Disease↗
PubMed2002

[Neo-adjuvant chemotherapy with carmofur for colorectal cancer--a multi-institutional randomized controlled study].

The efficacy and safety of preoperative chemotherapy with carmofur (HCFU) for colorectal cancer were evaluated in a randomized controlled study involving 63 institutes in the Kanto area. Patients aged 75 or younger with Dukes' B or C colorectal cancer were eligible if curative surgery was expected. In the end, 326 were eligible from 405 consecutive colorectal cancer patients. Patients in both the control (n = 162) and the new treatment group (n = 164) were given intravenous mitomycin C (MMC) 6 mg/m2 on day 0 and 7 after surgery and HCFU 300 mg/day orally from day 14 for a year. Patients in the new treatment group were also given oral HCFU for 14 days or more prior to surgery. All 326 patients were followed for 5 years or longer. Five-year overall and disease-free survival rates were not significantly different between the two groups (75.4% and 71.6% for the control, and 71.8% and 71.5% for the study group, respectively). In the subset analysis, neither cancer site nor nodal status affected the differences in overall- and disease-free survival rates between the groups. The present findings show no additional efficacy of preoperative chemotherapy with HCFU in survival from advanced colorectal cancer. Further investigations in terms of patient selection, treatment regimen, combined use of radiotherapy, and other factors would be required to determine the significance of preoperative chemotherapy against advanced colorectal cancer.

Aged↗
PubMed2002

[Predictive factors affect the choice of strategy for breast cancer surgery].

Predictive factors are those factors that predict the effects of chemotherapeutic or other agents on the tumor or the host. Many factors have been investigated for their predictive value of the effect of chemotherapeutic or hormonal agents. Estrogen or progesterone receptors are the most established predictive factors for hormonal therapy. Her-2/neu is a predictive of the effect of the monoclonal antibody trastuzumab and of certain chemotherapeutic agents. Other predictive factors remain under clinical investigation. Most cases of breast cancer are initially considered to be systemic disease. Cure can only achieved with surgery that leaves no residual cancer cells, followed by an appropriate form of systemic therapy. In the clinical situation, local therapy and systemic therapy for breast cancer have been considered independently. However, preoperative chemotherapy has become common recently. The interaction between chemotherapy and surgery should be considered because the results of preoperative chemotherapy affect the choice of operative technique. Predictive factors for the effect of radiation therapy should also be taken into account after breast-conserving surgery. It remains to be determined which predictive factors should be considered at which time.

Antineoplastic Agents, Hormonal↗
PubMed2002

[Infectious complications after esophageal surgery].

The incidence of wound infection, which is an intrasurgical field infection, is lower than the incidence of pneumonia, which is an extrasurgical field infection, after esophageal cancer surgery. Several trials predicting postoperative infectious complications have been reported. One measured the phytohemagglutinin- and concanavalin A-induced proliferation of peripheral blood mononuclear cells in patients; one measured the white blood cell (WBC) count 2 h after surgery and the decrease in WBC count on first postoperative day; and another showed that the decrease in serum IgG2 level can predict the occurrence of methicillin-resistant Staphylococcus aureus (MRSA) infections. Useful strategies for managing infectious complications have also been reported. Applying mupirocin calcium hydrate ointment to the nasal cavity decreases the incidence of MRSA infections. Autologous blood collection reduces the need for allogeneic transfusion in patients undergoing resection of esophageal cancer, and avoidance of allogeneic transfusion may reduce the risk of postoperative infection. The total exposure to preoperative chemoradiotherapy should be limited to 40 Gy or less to prevent postoperative pneumonia.

Blood Transfusion, Autologous↗
PubMed2000

Surgically treated Cronkhite-Canada syndrome associated with gastric cancer.

Cronkhite-Canada syndrome is generally accepted to be a benign disorder, with 374 reported cases to the present. Worldwide, there have been 18 previously reported cases of Cronkhite-Canada syndrome associated with gastric cancer. In this report we describe a case of a 52-year-old man with the clinical features of Cronkhite-Canada syndrome combined with gastric cancer. Although the gastric tumor was located at the antrum of the stomach, we performed a total gastrectomy because of the edematous swelling and high risk of malignancy in the remnant stomach. As Cronkhite-Canada syndrome may be a premalignant condition for gastric cancer, as well as for colorectal cancer, we suggest periodic examination of the stomach, colon, and rectum for patients with Cronkhite-Canada syndrome.

Journal Article↗
PubMed1999

Pyrimidine nucleoside phosphorylase and dihydropyrimidine dehydrogenase indicate chemosensitivity of human colon cancer specimens to doxifluridine and 5-fluorouracil, respectively.

We have assessed pyrimidine nucleoside phosphorylase (PyNPase) and dihydropyrimidine dehydrogenase (DPD) activity to compare the chemosensitivity of 5-fluorouracil (5-FU) and doxifluridine (5'-DFUR). Tumor samples were prepared from fresh surgical specimens of 28 patients with advanced colon carcinoma. The activity levels of the two enzymes were assessed as indicators of chemosensitivity to 5'-DFUR and 5-FU. PyNPase activity was analyzed using the HPLC method, and DPD activity was assessed according to the methods of Naguib et al. (1985). A histoculture drug response assay (HDRA) was conducted according to the methods described by Furukawa et al. (1992). The mean and standard deviation of PyNPase activity in the tumor tissue was 110 +/- 48.6 &mgr;g 5-FU/mg protein/h, which was statistically higher than the corresponding value obtained in normal tissue (60 +/- 43.1 &mgr;g 5-FU/mg protein/h) (P < 0.005). When chemosensitivity to the two drug forms was compared in 16 samples obtained from 16 cases with colon cancer, 1 specimen was sensitive to both drug forms, 3 specimens were exclusively sensitive to 5'-DFUR, 5 specimens were exclusively sensitive to 5-FU, and the other 7 specimens were insensitive to both drugs, without significance. High PyNPase activity was associated with a high chemosensitivity to 5'-DFUR, and high DPD activity correlated with a low chemosensitivity to 5-FU. However, the converse relationship was not found. We suggest that the activity of PyNPase and DPD represents a reliable indicator for the chemosensitivity of colon cancer to 5'-DFUR and 5-FU, respectively.

Journal Article↗
PubMed1999

Induction of secretion of interleukin-8 from human gastric epithelial cells by heat-shock protein 60 homologue of Helicobacter pylori.

Escherichia coli cells expressing fusion proteins consisting of beta-galactosidase and bacterial heat-shock protein (HSP) 60 of E. coli, Yersinia enterocolitica or Helicobacter pylori were constructed, and designated as HY1, HY2 or HY3, respectively. Fusion proteins prepared from HY2 and HY3 induced secretion of interleukin-8 (IL-8) from human gastric epithelial KATOIII cell cultures. On the other hand, the parent strain (E. coli pop2136), PEX (pop2136 transformed by vector) and fusion protein prepared from HY1 did not induce IL-8 secretion from KATOIII cells. Other human gastric (MKN45) and non-gastric cell lines (Int 407 and A549) did not secrete IL-8 following treatment with these proteins. These results indicate that H. pylori HSP60 induces IL-8 secretion from human gastric cells and the levels of IL-8 differ among the various gastric cell lines, suggesting that HSP60 might be an important virulence factor associated with chronic gastric inflammation following H. pylori infection in man.

Bacterial Proteins↗
PubMedDate not supplied

c-Jun N-terminal kinase activation during warm hepatic ischemia/reperfusion injuries in a rat model.

Ischemia/reperfusion injuries are a major problem in liver resections and transplantations. Tumor necrosis factor-alpha has been widely investigated as a key mediator in the mechanism of ischemia/reperfusion injury. Upstream signal transduction mechanisms for tumor necrosis factor-alpha have not been well documented. Therefore, we assessed c-Jun N-terminal kinase activation during warm hepatic ischemia/reperfusion injuries in a rat model. Male Wistar rats were subjected to 30 minutes of ischemia followed by reperfusion. Hepatic enzymes, histological examinations, microfluorographs, and tumor necrosis factor-alpha protein production (in the serum and liver tissue) were analyzed during the course of reperfusion. c-Jun N-terminal kinase activity was measured by a radioisotope kinase assay. Ischemia/reperfusion injuries were characterized by an elevation in hepatic enzyme, the histological degeneration of hepatocytes, and an increase in the number of nonviable cells. Moreover, increased endothelial-adherent leukocytes and tumor necrosis factor-alpha protein production were also observed. c-Jun N-terminal kinase activity at 60 minutes after reperfusion was 12.4 times higher than the pre-ischemia level. These results suggest that c-Jun N-terminal kinase may play some role in the mechanism of ischemia/reperfusion injuries.

Animals↗
PubMedDate not supplied

Erythrocytes with T-state-stabilized hemoglobin as a therapeutic tool for postischemic liver dysfunction.

This study aimed to examine if T-state stabilization of hemoglobin in erythrocytes could protect against postischemic organ injury. Human erythrocytes containing three different states of Hb allostery were prepared: control Hb (hRBC), CO-Hb that is stabilized under R-state with the 6-coordinated prosthetic heme (CO-hRBC), and alpha-NO-deoxyHb stabilized under T-state (alpha-NO-hRBC). To prepare alpha-NO-RBC, deoxygenated RBC was treated with FK409, a thiol-free NO donor, at its half molar concentration to that of Hb; this procedure resulted in the 5-coordinated NO binding on the alpha-subunit heme, as judged by electron spin resonance spectrometry. Rats were subject to 20 min systemic hemorrhage to maintain mean arterial pressure at 40 mm Hg, and reperfused with one of hRBCs. This protocol for ischemia, followed by 60 min reperfusion with physiological saline, caused modest metabolic acidosis and cholestasis. Administration of hRBC or COhRBC significantly attenuated cholestasis and improved acidosis. Rats treated with alpha-NO-hRBC exhibited greater recovery of metabolic acidosis and bile excretion than those treated with hRBC or CO-hRBC, displaying the best outcome of local oxygen utilization in hepatic lobules. Half-life time of alpha-NO-RBC administered in vivo was approximately 60 min. These results suggest that T-state Hb stabilization by NO serves as a stratagem to treat postischemic organ dysfunction.

Acidosis↗