Biomedical subjects
Publications and source records attributed to H Fujii.
Fourteen year old female visited our hospital suffering from anterior chest pain. Chest CT revealed anterior mediastinal mass which had multiple cystic lesions, 8.5 x 7.0 x 5.5 cm in size. Tumor extirpation had performed by median sternotomy and pathological diagnosis was mature teratoma. CA 19-9 and CEA in the cystic fluid had elevated 32,790 U/ml and 768 ng/ml, respectively.
Transbronchial needle aspiration (TBNA) is a bronchoscopic technique to obtain cytologic and histologic specimen from deep site of bronchial wall. We investigated the utility and safety of TBNA in 200 patients who had mass lesions in the lung or in the mediastinum. 101 patients had submucosal or peribronchial malignant lesions (central malignancy) and TBNA was the only diagnostic method in 28 patients (28%). 39 patients had peripheral malignant lesions (peripheral malignancy) and TBNA was the only diagnostic method in 12 patients (31%). The other 60 patients had benign lesions and TBNA was diagnostic in only 5 patients (8%); bronchogenic cyst in 2, tuberculous lymph adenitis in 1, parathyroid adenoma in 1 and lung abscess in 1. In central malignancy, the yield of TBNA as exclusive means of diagnosis was higher for mediastinal tumor than for lung cancer. In peripheral malignancy it was higher for metastatic lung tumor than for primary lung tumor. In order to stage patients of lung cancer, we sampled 39 lymph nodes and 21 of them were proved to be positive. TBNA was thought to be of greatest value in the diagnosis of peritracheal mediastinal tumor and peribronchial metastatic lung tumor and in the staging of lung cancer. We used 19-gauge transbronchial histology needle in 8 patients and 2 cases were diagnostic. Low diagnostic yields were probably due to the lack of our experience and it was expected that training on this technique would increase diagnostic utility of the histology needle. No significant complications occurred and all patients tolerated TBNA well.
This report describes a successful operative case of tricuspid infective endocarditis in a drug addict. A 24-year-old man with a history of drug addiction (6 months) complained of general fatigue and high fever. Echocardiography showed a large vegetation attached to the tricuspid valve and severe tricuspid regurgitation. Blood cultures revealed septicemia due to methicillin sensitive Staphylococcus aureus. He was treated for about 1 week with intravenous antibiotics. However, subsequent severe heart failure necessitated emergency operation. The tricuspid valve was replaced with Carpentier-Edwards bioprosthesis because of severe destruction of the tricuspid valve. The postoperative course was uneventful and he has remained free from endocarditis for 15 months after surgery.
We report two cases of prosthetic valve endocarditis which were successfully treated with aortic root replacement using the freestyle stentless bioprosthesis. Prosthetic valve endocarditis occurred in two patients after aortic valve replacement and modified Bentall operation, respectively. The aortic annulus was severely damaged and left ventriculo-aortic discontinuity was found in both cases. We used the freestyle stentless bioprosthesis, which fits well to the destroyed aortic annulus with left ventriculo-aortic discontinuity, because of its flexibility. Postoperative echocardiography revealed excellent hemodynamic results in both cases. Although the long-term results obtained with the freestyle stentless bioprosthesis, such as resistance to bacterial infection, have not been reported, this prosthesis appears to be very useful for treatment of prosthetic valve endocarditis. We expect that this prosthesis might be a option for PVE as an alternative to a homograft.
Although the sentinel node concept has been validated and clinically applied to breast cancer and malignant melanoma, its clinical significance in other solid tumors has not been thoroughly investigated. With regard to gastrointestinal (GI) cancers in particular, our surgeons have been cautious because of the high frequency of skip metastasis and the complicated lymphatic system in the GI tract. We would like to emphasize that so-called skip metastasis has been defined according to anatomic classification of regional lymph nodes and that the lymphatic drainage route must be patient or lesion specific. To test the validity and feasibility of this concept in GI cancers, we have established a radio-guided intraoperative sentinel node navigation system using preoperative endoscopic submucosal injection of radioactive tracer followed by intra-operative gamma-probing. In 131 patients with GI cancers (esophagus: 22, stomach: 71, colorectum: 38), the detection rate of sentinel nades was 91% and overall diagnostic accuracy of lymph node metastasis by sentinel node status was 97%. Initial results suggest further investigation of this procedure as an accurate staging and a minimally invasive approach to early GI cancers.
Escherichia coli cytosine deaminase (CD), which is a prokaryotic enzyme, converts nontoxic prodrug 5-fluorocytosine (5-FC) into the toxic chemotherapeutic agent 5-fluorouracil (5-FU). To investigate an enzyme/prodrug gene therapy for colorectal cancer, using adenoviral gene transfer of the E. coli CD gene associated with administration of 5-FC, we constructed replication-defective adenovirus vectors expressing the E. coli CD gene or lacZ gene driven by a CAG promoter (composed of a cytomegalovirus immediate early enhancer and a chicken beta-actin promotor). The present study demonstrated that an adenoviral gene transfer system using a CAG promoter induced sufficient gene expression of CD to confer the cytotoxicity of 5-FC to HT29 human colon cancer cells by converting it into 5-FU even at an moi of one. Furthermore, experimental gene therapy using intratumoral injection of the CD-expressing adenovirus with systemical administration of 5'-FC successfully suppressed the growth of established HT29 subcutaneous tumors in nude mice. These results suggest that enzyme/prodrug gene therapy using the adenoviral gene transfer of the E. coli CD gene with concomitant administration of 5-FC may be an effective strategy in the local control of colorectal cancer.
Chemotherapy plus granulocyte colony-stimulating factor (G-CSF) induced mobilization of peripheral blood stem cells (PBSC) was performed in patients with limited stage small-cell lung cancer. Chemotherapy consisted of cisplatin/etoposide or cisplatin/adriamycin/etoposide. The amounts of CD34 positive cells and granulocyte-macrophage colony forming units (CFU-GM) collected during 2-3 courses of apheresis were 3.1 +/- 2.9 x 10(6)/kg (n = 10) and 3.1 +/- 1.5 x 10(5)/kg (n = 8), respectively. Adequate amounts of PBSC were also harvested even in patients treated with concurrent chemoradiotherapy. Eight patients were successfully treated with high-dose chemotherapy consisting of ifosfamide, carboplatin and etoposide with PBSC transfusion. The patients'-bone marrow reconstruction was rapid and no treatment-related death was observed.
A 68-year-old female underwent radical mastectomy for left breast cancer in April, 1995. She was treated with conventional combination chemotherapy (CEF) before and after surgery as an adjuvant therapy. She was treated with oral tamoxifen (TAM) and/or medroxyprogesterone (MPA) and doxifluridine daily after surgery. In May, 1998, she was found to have developed a subcutaneous tumor of the head and skull-bone, and a meningeal metastasis. We treated her with 80 mg docetaxel (TXT) one time with radiation (total dose 50 Gy), and with 70 mg two times. After the combination therapy, she achieved partial remissions of the metastases and a decrease in serum CEA. Adverse reactions to TXT were grade 3 alopecia, grade 3 to 4 neutropenia, grade 2 to 3 stomatitis, and grade 2 diarrhea. All were tolerable and reversible. The combination therapy of radiation and TXT may be a good strategy for recurrent breast cancer.
We report here the first case of localized amyloidosis of the ureter and bladder to be treated effectively by occlusive dressing technique therapy using dimethyl sulfoxide. The patient was a 48-year-old woman whose chief complaint was macrohematuria and right back pain. Ultrasound sonography demonstrated right hydronephrosis and an intravesical mass in the region of the right ureteral orifice. Retrograde pyelography revealed severe stricture of the right lower ureter. Cystoscopy demonstrated a yellow submucosal tumor around the right ureteral orifice. We suspected urinary tract amyloidosis, and transurethral biopsy and resection of the intravesical mass were performed under right ureteral stenting. Histopathological diagnosis was amyloidosis. There was no evidence of systemic amyloidosis. To treat residual amyloidosis of the ureter and bladder, we performed occlusive dressing technique therapy using dimethyl sulfoxide every day. After 6 months of therapy, the right hydronephrosis disappeared, and there was no evidence of a recurrence of amyloidosis. We concluded that this therapy was very effective and safe for urinary tract amyloidosis.
Evidence based medicine is essential to further develop the state of the art for cancer treatments. We introduce the levels of evidence for Taxotere treatment against various solid tumors. Most evidence for Taxotere therapy was produced in other countries. However, in Japan we have some data from phase II clinical trials for the approval of Taxotere. We review these domestic results, which reveal its usefulness and toxicity in Japanese patients. In addition, we analyze the evidence from the data of clinical trials of Taxotere conducted by investigators in the USA/Europe. Japanese physicians or academies must build a consensus for the application of Taxotere to Japanese patients with solid tumors.
Medroxyprogesterone acetate (MPA) is a drug commonly used in endocrine therapy for advanced or recurrent breast cancer and endometrial cancer. The drug is extensively metabolized in the intestinal mucosa and in the liver. Cytochrome P450s (CYPs) involved in the metabolism of MPA were identified by using human liver microsomes and recombinant human CYPs. In this study, the overall metabolism of MPA was determined as the disappearance of the parent drug from an incubation mixture. The disappearance of MPA in human liver microsomes varied 2.6-fold among the 18 samples studied. The disappearance of MPA in the same panel of 18 human liver microsomes was significantly correlated with triazolam alpha-hydroxylase activity, a marker activity of CYP3A (r = 0.764; P < 0.001). Ketoconazole, an inhibitor of CYP3A4, potently inhibited the disappearance of MPA in 18 human liver microsomes. Anti-CYP3A antibody also inhibited 86% of the disappearance of MPA in human liver microsomes. Although sulfaphenazole (an inhibitor of CYP2C9) and S-mephenytoin (an inhibitor of CYP2C19) partially inhibited the disappearance of MPA, no effect of the anti-CYP2C antibody was observed. The disappearance of MPA did not correlate with either the activity metabolized via CYP2C9 (diclofenac 4'-hydroxylase activity) or the activity metabolized via CYP2C19 (S-mephenytoin 4'-hydroxylase activity). Among the 12 recombinant human CYPs (CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP3A4, and CYP3A5) studied, only CYP3A4 showed metabolic activity of MPA. These results suggest that CYP3A4 is mainly involved in the overall metabolism of MPA in human liver microsomes.
BACKGROUND: The purpose of this study was to evaluate the performance of two homogeneous assays for LDL-cholesterol (LDL-C), a polyethylene/cyclodextrin (PC) assay and a detergent (D) assay, which are based on different principles, in cholestatic serum. METHODS: We compared serum LDL-C concentrations determined by the two assays for healthy normolipidemic subjects (n = 42) and cholestatic patients (n = 51). LDL-C concentrations obtained with the homogeneous assays were also compared with those obtained by HPLC for patients' sera. In the interference study, conjugated bile acids were added to normal serum, and their effects on the two assays were examined. The effects of lipoprotein-X (LP-X), intermediate-density lipoprotein (IDL), and apolipoprotein (apo) E-rich HDL on the LDL-C assays were also investigated by adding these lipoproteins to normal serum. RESULTS: The LDL-C concentrations obtained with the D assay were higher than those obtained with the PC assay in the serum with high LP-X. The bias for LDL-C vs LP-X in cholestatic serum correlated with LP-X concentration (r = 0.582; P: <0.0001; n = 51). In the interference study, no effect of bile acids on the LDL-C assays was observed. However, the D assay measured 51.0% of the cholesterol in LP-X, whereas no reactivity was observed for LP-X in the PC assay. In addition, the D assay and the PC assay measured IDL-cholesterol at 31.2% and 52.4%, respectively, and measured apo E-rich HDL-C at 7.6% and 17.8%, respectively. CONCLUSIONS: Although both homogeneous LDL-C assays are suitable for most cases, the present study showed that each homogeneous assay has a different limitation for cholestatic serum with gross alterations in lipoproteins.
We investigated the incidence of post-transplant solid tumors in a cohort of 109 patients who had undergone auto-peripheral blood stem cell transplantation (PBSCT) for acute myelogenous leukemia (n = 18), acute lymphoblastic leukemia (n = 7), non-Hodgkin's lymphoma (n = 52), Hodgkin's disease (n = 5), multiple myeloma (n = 16), chronic myelogenous leukemia (n = 1), myelodysplastic syndrome (n = 3) and solid tumors (n = 7). The patients were followed up for a median of 32 months after PBSCT. Five second solid malignancies developed in 4 patients within 14 to 43 months after PBSCT: large cell carcinoma of the lung, adenocarcinoma of the rectum, cholangiocellular carcinoma of the liver, squamous cell carcinoma of the mouth, and adenocarcinoma of the gallbladder. The affected patients were 3 of 52 with non-Hodgkin's lymphoma and one of 16 with multiple myeloma. One of the patients was in the 5th decade of life (n = 31) and 3 were in the 6th decade (n = 31). The cumulative actuarial risk for developing post-transplant solid tumors was 8% at 8 years. Elderly patients (> or = 60 year old) who have undergone PBSCT need to be observed carefully for second neoplasms because of their increased risk of post-transplant solid tumors.
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The objectives of the present study were to evaluate whether a schedule-dependent pharmacokinetic and/or pharmacodynamic interaction exists between two sequences of docetaxel and doxorubicin administration and to determine the maximal tolerated dose (MTD) of this combination. Patients with chemotherapy-naïve metastatic or recurrent advanced breast cancer were enrolled. In the crossover design, tandem dose escalation of docetaxel and doxorubicin was performed. Docetaxel, in doses ranging from 50-70 mg/m2, was administered for 1 h by drip infusion either just before or after a 5-min bolus i.v. injection of doxorubicin at dosages from 40-50 mg/ m2. The sequence of drug administration was switched after the first course in each patient, and the sequence of drug administration thereafter depended on the patient's choice. Twenty-five patients were initially assessable for toxicity. The MTD in the sequence of doxorubicin after docetaxel was 40 and 50 mg/m2, respectively, with the dose-limiting toxicity of neutropenia. On the other hand, the MTD of the sequence of docetaxel after doxorubicin was 70 and 50 mg/m2, respectively. The dose-limiting toxicities in this sequence were neutropenia and diarrhea. Duration of grade 4 neutropenia in the sequence of docetaxel followed by doxorubicin was significantly longer than that in the alternate sequence (P = 0.0062). However, there was no difference in pharmacokinetic parameters of docetaxel, doxorubicin, and doxorubicinol between the two sequences. The sequence of 50 mg/m2 doxorubicin followed by 60 mg/m2 docetaxel is recommended for subsequent clinical trials for practical reasons.
BACKGROUND: In this study, radiofrequency (RF) induction heating therapy using a self-expanding Gianturco metallic stent (G-EMS) to treat acute aortic dissection was evaluated. METHODS: We evaluated convergent RF induction heating of G-EMS in pigs. In group A (n=3), an aortic dissection was created to determine the natural course of this lesion. In group B (n=4), 0.40 mm stainless steel bare G-EMSs (2.5 cm, 10 bends) were placed in the aorta 5 to 7 days after dissection, and RF induction heating was performed for 30 (n=2) or 45 (n=2) minutes. In group C (n=6), G-EMSs with 0.10 mm ferro-chrome wire mounted on alternating stent legs were placed in the aorta 1 to 7 days after dissection, and RF induction heating was performed for 10 minutes. RESULTS: In group A, 2 pigs died from rupture of the false lumen. In group B, fusion of the dissection flap was confirmed histologically. However, all of the pigs died. In group C, all of the pigs tolerated the procedure, and fusion of the dissection flap was confirmed in all of the pigs. CONCLUSIONS: This experimental animal study suggested that RF induction heating combined with G-EMS, if properly applied, has a potential to treat acute aortic dissection.
We report a case of Hodgkin's disease that developed 4 years after autologous peripheral blood stem cell transplantation (PBSCT). The patient, a 67-year-old Japanese male, underwent PBSCT for multiple myeloma (IgA-lambda type) under a conditioning regimen of carboplatin, etoposide and cyclophosphamide in June 1994 and obtained partial remission. In January 1995, he underwent a second PBSCT under a conditioning regimen of high-dose melphalan and obtained complete remission. In December 1998, he noticed swelling of the left cervical lymph nodes, and Hodgkin's disease of the mixed cellularity subtype was diagnosed from a lymph node biopsy sample. Immunohistochemistry studies showed that the Hodgkin's and Reed-Sternberg cells were CD30-positive. In situ hybridization using EBER probes showed that these cells expressed EBER RNA transcripts, indicating that the tumor was associated with Epstein-Barr virus. One noteworthy feature was the absence of both M-component in the serum and urine, as revealed by immunoelectrofixation, and plasmacytosis in the bone marrow, which would have indicated relapse of the multiple myeloma. After chemotherapy with MOPP and ABVD, the Hodgkin's disease was eradicated and the patient obtained complete remission in May 1999.
Because fluorine-18 fluorodeoxyglucose (18F-FDG) is an excellent tumor-localizing radio-pharmaceutical, a hand-held radiation detection probe capable of localizing an area with high 18F-FDG uptake would make radioguided surgery possible. In this laboratory study, we investigated the capability of a widely used intraoperative gamma probe with a cadmium zinc telluride (CdZnTe) detector for detection of 18F-FDG. For sensitivity tests, an 0.1- ml 18F-FDG preparation was made to act as a point source with radioactivities of 1.0, 2.0, and 3.0micro Ci (37 kBq, 74 kBq, 111 kBq). Relative transmission across the side wall of the probe and sensitivity at each source-to-probe distance were measured. For simulation studies, 2 l of 18F-FDG solution (0.02micro Ci, 0.74 kBq/ml) served as normal background. One ml of 18F-FDG was prepared to simulate tumors with radioactivities of 0.05, 0.1, 0.2, and 0.4micro Ci (1.85 kBq, 3.7 kBq, 17.4 kBq, and 14.8 kBq). The ratios of the radioactive concentration of tumor to that of the background were 2.5, 5, 10, and 20:1, respectively. The tested gamma probe was shown to be sensitive to 18F. The high-energy annihilation radiation was detected from the side wall of the probe despite application of a supplementary collimator. The count rate decreased markedly as the source-to-probe distance increased, owing to the effects of the inverse-square law. In the simulation studies, the probe detected a considerable amount of background activity. However, the measured count rate increased with the increasing source-to-background ratio. In our setting, the probe was capable of distinguishing the 18F-FDG source from the background when the source-to-background ratio was no less than 5:1. To make a surgical application feasible, however, collimation or shielding against high background radiation is necessary.