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Biomedical subjects

T Ochiai

Publications and source records attributed to T Ochiai.

At least 109 records · Page 6Linked to original sources

[Two cases of methicillin-resistant Staphylococcus aureus (MRSA) sepsis following craniotomy].

We report here two cases of MRSA sepsis following craniotomy. In case 1, a petroclival meningioma was subtotally removed and lumbar drainage was inserted postoperatively to prevent cerebrospinal fluid leakage. Ventriculo-peritoneal shunt was performed after meningitis was treated with vancomycin and panipenem/betamipron. Two weeks after the procedure, the patient revealed continuous spiking fevers related to MRSA sepsis, which did not improve with vancomycin and arbekacin administration. The focus of infection was found by scintigraphy and CT by 67Ga to be spondylo-diskitis at the level of L2-L3. The lesion was removed and bone from the iliac crest grafted. In case 2, seven days after surgery for multiple meningioma, the patient exhibited spiking fevers and swelling in the left leg. The central venous catheter was removed from the left femoral vein and MRSA was found from blood culture. The patient was treated with arbekacin (200 mg/day). Venous thrombosis diagnosed by CT was treated with heparin. Symptoms related to the infection and laboratory data did not improve because the concentration of arbekacin in the blood did not reach an effective level. The symptoms markedly improved when the dose of arbekacin was doubled (400 mg/day).

Adult↗

[X-ray and endoscopic diagnosis of esophageal achalasia].

We evaluated diagnostic X-ray and endoscopic examination findings in 486 patients with esophageal achalasia. Concerning the association between the duration of disease and the X-ray dilatation type, the duration was 1-4 years in more than 50% of patients with the Sp type, a mean of 8.5 years in those with the F type, and frequently more than 10 years in those with the S type. Endoscopy is generally used to determine the presence or absence of abnormal movement. In achalasia, the endoscope can be inserted into the stomach despite resistance at the stenotic site, and the mucosal surface is normal. Squamous cell carcinoma as a complication was observed in 21 patients (4.3%). The carcinoma complication rate was higher with a longer duration of disease and a longer observation period. The mean total course including the postoperative course was 27 years. Long-term and periodic X-ray and endoscopic observation of the disease course is important, and iodine staining is indispensable for early detection of esophageal cancer.

Adolescent↗

[Clinical significance of serum p53 antibody detection in a chemosensitivity assay in cases of human colorectal cancer].

Alteration of the p53 gene product occurs frequently during the progression of colorectal cancer. Recently, mutated p53 protein was found to induce the production of anti-p53 antibodies in the serum of patients. The purpose of this study was to evaluate the relationship between p53 status in serum and chemosensitivity in resectable colorectal cancer patients. A total of 35 patients with primary colorectal cancer who underwent surgical treatment were examined by chemosensitivity test with the viable tumor samples using Histoculture Drug Response Assay (HDRA). Serum samples of these patients to test for p53 antibodies were obtained before tumor resection, and assayed in duplicate by using an enzyme-linked immunosorbent assay (ELISA) kit. The inhibition index of 5-FU and CDDP, determined by the HDRA method, in the sero-positive group was significantly lower than that of the sero-negative group (p < 0.01). Furthermore, significant statistical differences in chemosensitivity to 5-FU and CDDP were revealed depending on the presence of serum p53 antibodies. There was no relationship between chemosensitivity assay and tumor marker positivity or clinicopathological features in these patients. Detection of serum p53 antibodies, which reflects p53 mutations in tumor tissue, is a simple method which correlates with chemosensitivity, and may contribute to the selection of favorable chemotherapeutic strategies of colorectal cancer.

Antineoplastic Agents↗

[The protocol of clinical trial and basic experiments for esophageal cancer using gene transduction].

We examined whether antitumor effect could be produced by retrovirally expressed interleukin-2(IL-2) gene, glanulocyte macrophage-colony stimulating factor(GM-CSF) gene, herpes simplex virus-thymidine kinase(HSV-tk) gene and p53 gene in human esophageal cancer cells using nude mice. Loss of tumorigenicity of IL-2 or GM-CSF producing cancer cells were observed. The antitumor effect was also evidenced by the injection of these cells into established tumors of wild-type cells. In suicide gene therapy on esophageal cancer, the growth suppression of esophageal cancer cells transducing HSV-tk gene tumors in nude mice induced by ganciclovir treatment and all the tumors disappeared. The wild-type p53 transduced tumor cells became markedly susceptible to irradiation and anticancer agents. Administration of cisplatine noticeably suppressed the growth of p53 transduced tumors inoculated in nude mice. We established the clinical protocol of gene therapy for esophageal cancer using wild-type p53 gene with adenovirus vector. In this autumn we are going to start this clinical trial.

Animals↗

[Intra-arterial infusion chemotherapy with docetaxel for locally advanced breast cancer and inflammatory breast cancer].

From 1998 to 2000, we performed neoadjuvant intra-arterial infusion chemotherapy using docetaxel (60 mg/m2) a few times with 5 patients with local advanced breast cancer and inflammatory breast cancer. Therapeutic effects included 3 cases of PR among the breast tumor patients and downstaging was obtained 2 cases. No critical side effects were found due to this chemotherapy. We could perform mastectomy in all the cases. We consider intra-arterial infusion using docetaxel to be highly effective with few side effects in cases of advanced breast cancer.

Adenocarcinoma↗

[Analysis of cases of complete response (CR) in esophageal and gastric cancer].

We investigated 117 patients with advanced esophageal cancer who had undergone radio-chemotherapy from 1990 to 2000 in our department. Concurrent radiotherapy with chemotherapy improved the response rate, and adjuvant surgery improved the prognosis. Future problems are the establishment of a method to estimate the sensitivity of tumors to chemotherapy or radiotherapy, the improvement of diagnostic methods for evaluation of the effect and the development of new therapies and regimens for non-responders in the present radio-chemotherapy group. The CR cases of inoperable, noncurative and recurrent patients with gastric cancer in the past decade were examined. A CR of the lymph nodes was obtained in 5 cases, and that of the hepatic metastasis and peritoneal recurrence was observed in one case each. However, a CR of the primary lesion has not been attained. Though re-swelling of the lymph nodes was not observed in 4 out of 5 CR cases, a maintenance treatment after CR should be established. Topical treatment is promising for the hepatic metastasis and peritoneal seeding. Since it is difficult to attain a CR of the primary lesion, surgical resection is required to prolong the survival time.

Antineoplastic Combined Chemotherapy Protocols↗

Cutting edge: inhibition of experimental tumor metastasis by dendritic cells pulsed with alpha-galactosylceramide.

A unique lymphoid lineage, Valpha14 NKT cells, bearing an invariant Ag receptor encoded by Valpha14 and Jalpha281 gene segments, play crucial roles in various immune responses, including protective immunity against malignant tumors. A specific ligand of Valpha14 NKT cells is determined to be alpha-galactosylceramide (alpha-GalCer) which is presented by the CD1d molecule. Here, we report that dendritic cells (DCs) pulsed with alpha-GalCer effectively induce potent antitumor cytotoxic activity by specific activation of Valpha14 NKT cells, resulting in the inhibition of tumor metastasis in vivo. Moreover, a complete inhibition of B16 melanoma metastasis in the liver was observed when alpha-GalCer-pulsed DCs were injected even 7 days after transfer of tumor cells to syngeneic mice where small but multiple metastatic nodules were already formed. The potential utility of DCs pulsed with alpha-GalCer for tumor immunotherapy is discussed.

Animals↗

Clinical significance of serum p53 antibody detection on chemosensitivity assay in human colorectal cancer.

BACKGROUND AND OBJECTIVES: Alteration of the p53 gene product occurs frequently during progression of colorectal cancer. Recently, mutated p53 protein was found to induce the production of anti-p53 antibodies in the serum of patients. The purpose of this study was to evaluate the relationship between p53 status in serum and chemosensitivity in resectable colorectal cancer patients. METHODS: A total of 22 patients with primary colorectal cancer who underwent surgical treatment were examined for chemosensitivity with iable tumor samples using the Histoculture Drug Response Assay (HDRA). Serum samples of these patients for p53 antibodies were obtained before tumor resection and assayed in duplicate using an enzyme-linked immunosorbent assay kit. RESULTS: The inhibition index of 5-fluorouracil and cis-diamminedichloroplatinum (CDDP), determined by the HDRA method, in the seropositive group was significantly lower than that in the seronegative group (P < 0.01). Furthermore, significant statistical differences in chemosensitivity to 5-fluorouracil and CDDP were revealed depending on the presence of serum p53 antibodies. CONCLUSIONS: Detection of serum p53 antibodies, which reflects p53 mutations in tumor tissue, is a simpler method which correlates with chemosensitivity and may contribute to the selection of favorable chemotherapeutic strategies for colorectal cancer.

Adenocarcinoma↗

Peritoneal lavage cytology findings as prognostic factor for gastric cancer.

The validity of lavage cytology for accurate gastric cancer staging is demonstrated in this study. Between 1988 and 1996, 29 cases (8. 4%) were revealed as positive among 347 patients with resectable gastric cancer in whom peritoneal lavage cytology was performed. The survival rate of cytology-positive patients in each stage was found to be worse than that of all other patients in the same stage. The prognostic factors selected by the univariate analysis were enrolled for multivariate analysis using Cox's proportional hazards model with the backward stepwise procedure. As a result, although cytology finding was selected as an independent prognostic factor, macroscopic finding of dissemination was not selected. Our data indicate that positive cytology findings indicated a poor prognosis, and therefore the results of peritoneal lavage cytology should be included as a factor in gastric cancer staging.

Analysis of Variance↗

Importance of positive peritoneal lavage cytology findings in the stage grouping of gastric cancer.

Although peritoneal lavage cytology is widely performed during surgery for gastric cancer and the results have been reported to be one of the accurate prognostic factors, the cancer stage is determined independent of the results of lavage cytology according to the First English Edition of Japanese Classification of Gastric Carcinoma. In this study we demonstrated the validity of lavage cytology for accurately staging gastric cancer. Between 1988 and 1996, peritoneal lavage cytology was performed in 347 patients with resectable gastric cancer. Among them, cytology was positive in 29 cases (8.4%). The survival rate of the cytology-positive patients in each stage was worse than that of all patients in the same stage. The prognosis of patients with positive cytology findings and serosa-exposed gastric cancer was significantly worse than that of negative cytology findings and serosa-exposed gastric cancer, and similar to that of negative cytology findings and serosa-infiltrating gastric cancer. Our data indicated that positive cytology findings thus indicated a poor prognosis, and the prognostic difference between positive and negative cytology findings was approximately a one-stage difference in the Japanese stage grouping. Based on our findings, the results of peritoneal lavage cytology should thus be included in the factors for staging gastric cancer.

Ascitic Fluid↗

The p53 gene mutation is of prognostic value in esophageal squamous cell carcinoma patients in unified stages of curability.

BACKGROUND: The p53 gene alteration is identified in approximately half of all human tumors, and is now thought to be a key gene for regulating the cell cycle through the induction of p21(WAF1/CIP1) and inducing apoptosis through some genes such as BAX. In this study, we investigated the prognostic value of p53 mutation for postoperative esophageal squamous cell carcinoma patients. METHODS: The subjects studied were 42 esophageal squamous cell carcinoma patients who underwent esophagectomy with complete curability in our department. The cases were limited to stage II and III. DNA was extracted from paraffin-embedded tissues. A p53 gene mutation was detected by polymerase chain reaction-single strand conformation polymorphism and subsequent direct sequencing method for exons 5 to 9. The 5-year survival rate was calculated and statistically compared between the p53 mutation(+) and (-) groups by the log rank test. RESULTS: The p53 gene mutation was identified in 14 cases (33.3%). The 5-year survival rate of the p53 mutation(-) group (n = 28) was significantly higher than the (+) group (n = 14; 51.0% versus 35.7%, P <0.05 by the log rank test). Recurrence could be identified in 10 of 14 p53 mutation(+) cases (71.4%), whereas it was found in 12 of 28 (-) cases (42.8%). CONCLUSION: The current study indicated that p53 mutation of tumor tissues might be a prognostic factor for esophageal squamous cell carcinoma cases and one of the risk factors for its recurrence.

Carcinoma, Squamous Cell↗

The role of Bcl6 in mature cardiac myocytes.

OBJECTIVE: The Bcl6 gene encodes a sequence-specific transcriptional repressor and is ubiquitously expressed in adult murine tissues including heart muscle. The objective of this study was to examine the role of Bcl6 in cardiac myocytes. METHOD: We developed Bcl6-deficient (Bcl6-/-) mice and histologically examined hearts from these mice. RESULTS: Massive myocarditis with eosinophilic infiltration occurred in Bcl6-/- mice after 4-6 weeks of age. Since expression of the Bcl6 gene was induced in normal cardiac myocytes after 2 weeks of age and thereafter detected through adulthood, loss of Bcl6 in mature cardiac myocytes may be related to the induction of eosinophilic myocarditis. To examine the effects of eosinophils from Bcl6-/- mice on normal hearts, bone marrow cells from Bcl6-/- mice were adoptively transferred into sublethally irradiated RAG1-deficient mice. Although massive eosinophilic infiltration was detected in conjunctivas and spleens from the chimeric mice, myocarditis was never observed. Electron microscopic analysis of cardiac myocytes from Bcl6-/- mice revealed a spectrum of degenerative changes prior to eosinophilic infiltration. CONCLUSION: Bcl6 maynot be essential for the maturation of cardiac myocytes but may play a role in protecting mature cardiac myocytes from eosinophilic inflammation.

Adoptive Transfer↗

Risk of bile duct carcinogenesis after excision of extrahepatic bile ducts in pancreaticobiliary maljunction.

BACKGROUND: A reflux of pancreatic juice into the biliary tract caused by pancreaticobiliary maljunction (PBM) has been considered important in the development of biliary tract carcinogenesis in choledochal cysts. We excised extrahepatic bile ducts in patients with choledochal cysts to terminate the reflux of pancreatic juice. We investigated whether this surgery could stop the development of the residual bile duct carcinoma. METHODS: Fifty-six patients with a diagnosis of PBM with choledochal dilatation underwent surgical excision of extrahepatic bile ducts. We applied a person-year method to compare the relative risks (observed number/expected number) of biliary tract carcinoma before and after surgery. RESULTS: In 3 patients, bile duct carcinoma developed in residual dilated segments 19 years 6 months, 8 years 8 months, and 2 years 5 months, respectively, after surgery. Although the relative risk in the post-surgery group was slightly decreased by surgery, it was still high compared with that of the general population. CONCLUSIONS: The incidence of bile duct carcinoma is still high, even after excision of extrahepatic bile ducts in PBM patients with choledochal dilatation. For these patients, careful long-term follow-up is necessary, especially after operations that leave the dilated bile ducts, such as cases of Todani's type IV-A.

Adolescent↗

Human papillomavirus types 16 and 39 in a vulval carcinoma occurring in a woman with Hailey-Hailey disease.

A woman with Hailey-Hailey disease, suffering from carcinoma of the vulva, was examined by histology and for the presence of human papillomavirus (HPV) DNA by polymerase chain reaction (PCR) and in situ hybridization. Our diagnosis by histological examination revealed the vulval carcinoma to be a squamous cell carcinoma (SCC), adjacent to lesions of Hailey-Hailey disease and severe dysplasia/carcinoma in situ [vulval intraepithelial neoplasia (VIN) III]. The PCR with consensus primers for the L1 region (L1-PCR) successfully amplified HPV DNA using total DNA extracted from formalin-fixed and paraffin-embedded tissue specimens. Restriction fragment length polymorphism analysis and sequencing of L1-PCR products revealed HPV types 16 and 39. HPV 16-specific primers for the E6 region identified HPV 16 DNA. In situ hybridization analysis with biotinylated HPV 16 and 39 DNA probes revealed the presence of the HPV 39 genome in the nuclei of the tumour cells in the SCC. These results indicate that HPV 16 and 39 are associated with lesions in vulval carcinoma. Regarding the patient's susceptibility to infection in the case of Hailey-Hailey disease, there is a possibility that HPV was inoculated into the lesions of Hailey-Hailey disease and induced those of VIN III and SCC.

Aged↗