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Biomedical subjects

Kiyoshi Fujinami

Publications and source records attributed to Kiyoshi Fujinami.

At least 19 recordsLinked to original sources

[Questionnaire on suitableness and acceptableness of cancer notification in aged Japanese prostate cancer patients].

PURPOSE: In Japan, sometimes a patient with malignant fatal disease is not informed the diagnosis. We tried to investigate if the informed consent of cancer notification is acceptable and suitable for aged Japanese prostate cancer patients. MATERIALS AND METHODS: From January to June 2003, we distributed a questionnaire to outpatients who had been followed up for more than 6 months after the diagnosis of prostate cancer. These patients declared a wish to be notified the true diagnosis in their first visit to our department and were informed that they had prostate cancer just after the diagnosis. Ninety-one per cent of patients (54 patients, mean age was 74.8 +/- 6.1 years old) answered to our questionnaire. Clinical stage consisted of 14 cases of B1, 13 cases of B2, 15 cases of C, 3 cases of D1, and 9 cases of D2. The histopathological grade consisted of 6 cases of well differentiated carcinoma, 32 cases of moderately differentiated carcinoma, and 16 cases of poorly differentiated carcinoma. Eleven cases underwent total prostatectomy (B1 and B2) and 44 cases had androgen deprivation therapy. RESULTS: Seventy-six per cent of patients understood and accepted their illness within a few days. However, 11% of patients took more than 3 months to accept their malignant disease. They answered that they could accept their illness given with a relationship of mutual trust between themselves as patients and the medical staff, effective medical treatment, and with the help of their family. They also answered that the most important emotional support was given by their wives (46.3%) and doctors (27.8%). In the early days following the diagnosis, they worried about their remaining days, the risks or side effects of the treatment, their family, and their job. Several months following the diagnosis, they were concerned about recurrence of the disease, their family, medical expenses, and their old age. Those who did not worry at all doubled from 11.1% immediately after the diagnosis to 22.2% several months later. More than 90% of the patients were satisfied with our medical care. And none answered that they might have been happier without cancer notification. CONCLUSIONS: Cancer notification is acceptable and suitable in aged Japanese prostate cancer patients who declare a wish to know their malignant illness. A good relationship between the patients and the medical staff, and emotional support from the wife are important.

Aged↗

Neuroserpin (PI-12) is upregulated in high-grade prostate cancer and is associated with survival.

We carried out Genechip analysis using prostate cancer and non-malignant tissue to identify specific genes related to prostate cancer. We focused on neuroserpin (PI-12), which has been identified as one of the genes with high expression in prostate cancer. We analyzed the relationship between its expression pattern and clinical characteristics. Prostate cancer and normal prostate tissue were analyzed by Affymetrix GeneChip technology. We carried out real-time quantitative PCR on a total of 102 specimens: 45 of normal prostate, 45 of previously untreated prostate cancer (constituting 45 pairs of samples obtained at radical prostatectomy, with each pair dissected from the same prostate specimen) and 12 of recurrent hormone refractory prostate cancer (HRPC). Results showed that the neuroserpin gene was more highly expressed in prostate cancer than in normal prostate tissue. Neuroserpin expression in untreated prostate cancer was significantly higher than that in normal prostate. In HRPC it was significantly higher than that in untreated prostate cancer and normal prostate. In untreated prostate cancer, neuroserpin expression was significantly higher in high grade tumors such as poorly differentiated adenocarcinoma than in lower grade tumors such as well or moderately differentiated adenocarcinoma. Higher neuroserpin expression was associated with shorter recurrence-free survival after radical prostatectomy, shorter recurrence-free survival in HRPC patients and shorter overall survival in HRPC patients. The neuroserpin gene may be associated with the development, progression and aggressiveness of prostate cancer. Our present data suggests that higher neuroserpin expression may predict an unfavorable outcome after radical prostatectomy or hormone therapy.

Disease Progression↗

Receptor for advanced glycation end products (RAGE) and its ligand, amphoterin are overexpressed and associated with prostate cancer development.

BACKGROUND: Advanced glycation end products (AGE) are produced with normal aging. Recently, some reports indicated that the interaction between AGE and the cognate receptor (RAGE) has a role in cancer dependent. METHODS: We investigated RAGE and amphoterin mRNA expression in prostate cancer cell lines (DU145, PC-3, and LNCaP cells), hormone-refractory prostate cancer tissues, and paired untreated primary prostate cancer and normal prostate (including benign prostatic hypertrophy (BPH)) tissues using real-time quantitative PCR. Moreover, to confirm the AGE-RAGE interaction in prostate cancer, DU145 cells stimulated with AGE-bovine serum albumin (AGE-BSA) were examined by in vitro matrigel assay, cell viability assay, MTT assay, reverse transcription-polymerase chain reaction (RT-PCR), and Western blot. RESULTS: DU145 cells, a hormone-independent prostate cancer cell line, showed the highest RAGE mRNA expression. Amphoterin mRNA was expressed in all three cell lines. In prostate tissues, untreated prostate cancer tissue and hormone-refractory prostate cancer tissue showed higher RAGE and amphoterin mRNA expression than normal prostate tissue. The AGE-RAGE interaction induced the invasion and growth in DU145 cells stimulated with AGE-BSA. CONCLUSIONS: The AGE-RAGE interaction is important in prostate cancer development, and inhibition of this interaction has potential as a new molecular target for cancer therapy or prevention.

Blotting, Western↗

Primary testicular leiomyosarcoma.

We report a case of primary testicular leiomyosarcoma. A 76-year-old man, who complained of left scrotal swelling for 6 months, underwent radical orchiectomy. Microscopic examination revealed intratesticular leiomyosarcoma. The patient received no adjuvant therapy and at 12 months after surgery, there had been no recurrence. Primary leiomyosarcoma of the testis is extremely rare; this is the 9th case recorded worldwide.

Aged↗

Usefulness of ultrasensitive prostate-specific antigen assay for early detection of biochemical failure after radical prostatectomy.

BACKGROUND: In order to assess whether the prostate-specific antigen (PSA) nadir obtained with an ultrasensitive PSA assay can be used as a prognostic indicator for patients undergoing radical prostatectomy, we investigated it retrospectively. METHODS: Between October 1997 and July 2003, 46 patients underwent radical prostatectomy for prostate cancer at our institution. None of them received preoperative treatment. Levels of PSA were measured with an ultrasensitive PSA assay every 1-3 months after prostatectomy. Biochemical recurrence was defined as a PSA level of 0.2 ng/mL or higher. RESULTS: There was a significant difference in PSA nadir between the biochemical recurrence group and the no recurrence group (P < 0.001). The receiver operating characteristics (ROC) curve gave an optimal cut-off value for PSA nadir of 0.01 ng/mL, demonstrating a significant difference in biochemical recurrence after radical prostatectomy. No patient with a PSA nadir level <0.01 ng/mL showed biochemical failure, while 15 out of 22 patients with PSA nadir levels >or=0.01 ng/mL showed biochemical failure. CONCLUSION: The PSA nadir level obtained using an ultrasensitive PSA assay is an excellent predictor of biochemical recurrence after radical prostatectomy. Early detection of recurrence offers the possibility of early salvage therapy.

Aged↗

[Usefulness of extension of disease as a prognostic factor in relapsed prostate cancer patients of stage D].

OBJECTIVE: The prognosis of prostate cancer has been evaluated by clinical stage or pathological grade. PSA parameters including PSA density and PSA doubling time have not always precisely reflected the prognosis of prostate cancer. The aim of this study was to evaluate PSA parameters and extension of disease (EOD) grade as prognostic factors for relapsed prostate cancer. METHODS: The relationship between PSA parameters or EOD grade, and survival of 29 stage D patients with relapsed prostate cancer after initial hormone therapy was examined. RESULTS: Only EOD grade was an independent prognostic factor, even for cause-specific survival period and survival period after relapse. CONCLUSION: EOD grade was a significant prognostic factor, and in particular, very useful as a prognostic factor for patients with bone metastasis. PSA value was not always associated with tumor volume, and therefore it is not an independent prognostic factor.

Aged↗

[Comparison of value of free-to total prostate specific antigen, prostate specific antigen density and prostate specific antigen density of transition zone for diagnosis of prostate cancer in patients with a PSA level of 4.1-10 ng/ml].

PURPOSE: We evaluated the utility of free-to total PSA (F/T PSA) ratio, PSA density (PSAD) and PSA density of the transition zone (PSATZ) in diagnosis of prostate cancer with intermediate PSA level (4.1-10 ng/ml). PATIENTS AND METHODS: Between January 2000 and December 2003, systematic prostate biopsies were performed on 178 patients with intermediate PSA level. The clinical values of F/T PSA ratio, PSAD and PSATZ for the detection of prostate cancer were compared by using receiver operating characteristic (ROC) curves. RESULTS: Overall, 57 of the 178 (32%) patients had prostate carcinoma. The ROC curve analysis showed PSAD and PSATZ were superior to F/T PSA ratio in patients with intermediate PSA level. In patients with total prostate volume greater than 30 cm3, the area under the ROC curve for F/T PSA ratio was greater than that for PSAD and PSATZ. CONCLUSIONS: PSAD and PSATZ were more powerful predictors of prostate cancer than F/T PSA ratio in patients with intermediate PSA level. While F/T PSA ratio was effective for diagnosis of prostate cancer in prostate volume greater than 30 cm3.

Aged↗

[A case of therapy-related leukemia/myelodysplastic syndrome following treatment of refractory testicular germ cell tumor].

We report a patient with a refractory testicular non-seminomatous germ cell tumor (NSGCT) who developed therapy-related leukemia (TRL) after undergoing salvage chemotherapy and multiple operations for repeat recurrences. Fifty months after the initial therapy, pancytopenia and myeloblasts were observed in the patient's peripheral blood while the patient was undergoing salvage chemotherapy for a fifth recurrence. A bone marrow examination showed evidence of myelodysplastic syndrome (MDS) and refractory anemia with excess of blasts in transformation (RAEB in T) under French-America-British (FAB) classification. Cytogenetic 5q-/7q- abnormalities were also observed. The patient had received a total dose of 189g/m2 of Ifosfamide, 8,250mg/m2 of Etoposide and 1,450 mg/m2 of Cisplatin; therefore, he was diagnosed as having TRL/MDS. The patient has received induction chemotherapy for TRL with Cytarabine, Daunorubicin and Fludarabine while a bone marrow transplantation has been scheduled. Recently, TRL associated with chemotherapy are being reported with increasing frequency in the literature. Since early detection and treatment are necessary for the management of TRL, peripheral blood examinations should be performed after a diagnosis of refractory germ cell tumor has been made. If pancytopenia is detected, bone marrow and cytogenetic examinations should be immediately performed to rule out TRL.

Adult↗

[Combination chemotherapy with docetaxel and cisplatin in patients with hormone-refractory prostate cancer].

We investigated the efficacy of docetaxel and cisplatin for hormone-refractory prostate cancer (HRPC). Thirteen patients with HRPC were treated with 30 mg/m2 docetaxel weekly for 3 weeks and 70 mg/m2 cisplatin on day 1. Treatment was repeated every 21 days. They received 2 cycles and were evaluated for the responses to serum prostate-specific antigen (PSA) and tumor size. Ten (77%) of the 13 patients showed a 50% or greater decrease in PSA with a median time to progression of 3 months. One of the 2 patients with measurable soft tissue disease showed a reduction in disease. No severe toxicity of this regimen was observed. Combination chemotherapy with docetaxel and cisplatin in patients with HRPC was well tolerated and efficatious with a significant decrease in serum PSA and measurable disease.

Aged↗

[Observation policy for residual masses after chemotherapy for gonadal and extra-gonadal germ cell tumors].

Twenty-five patients with germ cell tumors who had marker-free residual masses after undergoing chemotherapy were followed for up to 10 years (median, 21 months). The primary tumor sites were the gonads in 20 patients (6 seminomas [SGCTs] and 14 non-seminomatous germ cell tumors [NSGCTs]) and extra-gonadal regions in 5 patients (5 NSGCTs). All residual masses were observed in patients with SGCT. Residual masses that were 2 cm or less in size were left unresected, while masses that were 5 cm or more in size were resected in patients with NSGCT lesions. The management of other residual masses was decided based on the size, shrinkage, and pathological findings of the tumors. Residual masses were resected in six of the patients with gonadal NSGCTs. Recurrence occurred in one of the six patients with gonadal SGCTs (chemotherapy shrinkage; 11 cm to 3.5 cm) and three of the four cases with extra-gonadal NSGCTs (embryonal cell carcinoma: 3 cm to 1 cm, embryonal cell carcinoma+york sac tumor: 5 cm to 4 cm, embryonal cell carcinoma+chorio carcinoma; 4 cm to 1.2 cm). None of the patients with gonadal NSGCTs experienced a recurrence. Considering the pathologic diagnosis, shrinkage, and international germ cell consensus classification, unnecessary resections of residual masses that were less than 5 cm in size after chemotherapy for gonadal NSGCT should be avoided. However, residual masses in extra-gonadal NSGCTs should be resected.

Adult↗

[Two cases of testicular cancer with low human chorionic gonadotropin (hCG) levels after treatment].

Some patients with testicular cancer exhibit low human chorionic gonadotropin (hCG) levels even after successful treatment. We report 2 patients with testicular cancer (2 non-seminomatous germ cell tumors [NSGCTs]) and low betahhCG levels with no recurrence after successful treatment. The first patient is a 45-year-old man with pulmonary and retroperitoneal lymph node metastases. During the first chemotherapy the hCG level decreased but remained at a low level. Salvage chemotherapy had no effect on the hCG level, but a low betahCG level persisted for 16 months. The second case is a 19-year-old man with testicular cancer with retroperitoneal lymph node metastases. The patient underwent an operation for residual masses after chemotherapy. Pathological findings showed necrotic tissue, and a low betahCG level persist for 160 months. A low hCG level does not necessarily meen residual malignancy. Patients with a low hCG level should be monaged carefully avoiding needless treatment.

Adult↗

Effectiveness of percent free prostate specific antigen as a predictor of prostate cancer detection on repeat biopsy.

BACKGROUND: The aim of this study was to identify predictors that can increase the accuracy of detecting prostate cancer on subsequent biopsies. METHODS: Between 1998 and 2003, a total of 235 men with prostate specific antigen (PSA) levels between 4.0 and 20 ng/mL underwent one or more systematic needle biopsies of the prostate. Of these men, 73 (31.1%) underwent one repeat biopsy and 26 (11.1%) underwent two or more repeat biopsies. We evaluated the results of prostate biopsies in relation to the morbidity of prostate cancer detected on repeat biopsies. RESULTS: Of the 73 men who underwent repeat biopsy, 16 (21.9%) had prostate cancer. Twenty-six men with one negative re-biopsy underwent two or more repeat biopsies, and five of these patients were found to have early stage prostate cancer. On repeat biopsy, there was a significant difference in percent free PSA between the cancer-detected group and the no-cancer-detected group (P < 0.01). A receiver operating characteristics (ROC) curve gave an optimal cut-off value for percent free PSA of 11%, demonstrating a significant difference in the cancer detection rate on repeat biopsy (P = 0.0009). Analysis of the data for re-biopsies showed that cancer-detected cases showed a raised PSA value and a simultaneously reduced percent free PSA (these differences were statistically significant). CONCLUSIONS: A low percent free PSA level increased the probability of a positive result in repeat biopsy. An increase in the accuracy of detecting cancer, especially on repeat biopsy, will promote the detection of more early stage prostate cancer.

Aged↗

[Safe retroperitoneoscopic radical nephrectomy with small incision for renal cell carcinoma].

PURPOSE: Retroperitoneoscopic radical nephrectomy (RRN) has been performed at Yokohama City University Medical Center since May 2002. Three surgeons have become skilled in performing RRN without major complications. We investigated the outcomes of the surgery and attempt to clarify whether the technique we adopted is suitable to perform this procedure safely. PATIENTS AND METHODS: Between May 2002 and June 2003, 14 patients suspected of renal cell carcinoma underwent retroperitoneoscopic radical nephrectomy at Yokohama City University Medical Center. The surgical procedure is shown below. In a lateral position, a lumbar oblique incision 6 cm long is made to approach the retroperitoneal space. Under direct vision, the ureter is dissected and Gerota's fascia is dissected from the peritoneum and the psoas muscle to signalize the subsequent dissection line. After the dissection, hand port device was attached to the skin and three 12 mm trocars were placed. The subsequent procedures are performed by retroperitoneoscopic surgery with carbon dioxide insufflation. The isolated kidney was removed through the incision that was made initially. We investigated the outcomes of this procedure. RESULTS: The mean surgical duration was 244.4 minutes and mean blood loss was 217.9 ml. Conversion to open surgery was required in one case due to bleeding and in one case due to incomplete management of a small artery. Blood transfusion was not required in any case. There were no major complications during the perioperative period. CONCLUSIONS: The three operators have become skilled in performing RRN safely with this technique.

Aged↗

[A case of well controlled renal small cell carcinoma with metastasis treated by intensive therapy].

A 18-year-old male visited hospital with macroscopic hematuria. Computed tomography showed slightly enhanced left renal tumor that was uncharacteristic for clear cell carcinoma, and radical nephrectomy was performed. Operative specimen revealed primary small cell carcinoma of the kidney. 18 months after operation, bone metastases were diagnosed. Chemotherapy including cisplatinum, etoposide and bleomycin and external irradiation was performed. This intensive therapy was effective for metastatic lesion. He is still alive for 55 months after diagnosis, and is the best controlled case around the world. To our knowledge, this is the 14th case as primary renal small cell carcinoma in the world literature.

Adolescent↗

[Retroperitoneal liposarcoma with reactive pleural effusion: a case report].

A case of retroperitoneal liposarcoma with reactive pleural effusion is reported. A 58-year-old male who complained of weight gain and edema had visited another clinic in May, 2002. Computed tomography revealed a retroperitoneal tumor, 11 x 9 x 9.5 cm in size, surrounding his right kidney and bilateral pleural effusion. Complete resection of the tumor and right kidney was performed with a transperitoneal approach. Though the tumor was limited within Gerota's fascia, we noted two liters of abdominal ascites. Surgical specimen was histologically diagnosed as well differentiated liposarcoma. The post operative course was uneventful. The pleural effusion disappeared, and serum total protein level was normalized. He has remained free of disease for one year.

Humans↗

[A case of primary choriocarcinoma of the bladder].

A 75-year-old man visited our hospital presenting with gross hematuria. Cystoscopy revealed a bladder tumor with coagulated blood and necrotic tissue at the dome. We resected the bladder tumor transurethrally. Pathologically, the tumor was shown to be a transitional cell carcinoma with choriocarcinomatous differentiation, G3, > or = pT2. Immunohistochemical staining showed human chorionic gonadotropin (HCG)-positive tumor cells. Just after surgery, the serum HCG-beta concentration was less than 0.1 ng/ml. Total cystectomy and an ileal conduit operation were performed. The histological classification was TCC, G3, pTis. In later blood chemistry tests, HCG-beta elevation was observed. Pulmonary metastases appeared on a chest X-ray, and combination chemotherapy with cisplatin and etoposide was administered. Although the serum HCG-beta decreased with one course of chemotherapy, it increased immediately thereafter. The patient died of the disease about 8 months after the total cystectomy. Autopsy revealed multiple metastases in the lungs, liver, kidneys, stomach, pancreas, thyroid gland, adrenal glands, heart, jejunum, and vertebral body (Th10). Lymph node metastases in the pulmonary hilum, mediastinum, and right submaxillary gland were also found.

Aged↗

Expression of AR associated protein 55 (ARA55) and androgen receptor in prostate cancer.

BACKGROUND: Androgen receptor (AR) transcription is modulated by several cofactors such as AR associated proteins (ARA) including ARA70, ARA54, and ARA55. ARA55 increases AR transcription and alters ligand specificity. We hypothesized that ARA55 might play an important role in prostate cancer development or progression. We evaluated the messenger RNA (mRNA) expression of ARA55 in prostate cancer tissues, and analyzed the relation between ARA55 expression and clinical characteristics. METHODS: A total of 30 prostate cancer specimens (20 previously untreated prostate cancers and 10 recurrent, hormone-refractory prostate cancers (HRPC)) and 5 benign prostatic hypertrophy (BPH) tissue samples were examined. mRNA expression of ARA55 and AR were analyzed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) using real time PCR. RESULTS: ARA55 expression was identified in all tissue samples of previously untreated prostate cancer, HRPC and BPH. ARA55 expression level in HRPC specimens was significantly lower than that in previously untreated prostate cancer (P = 0.02) or BPH (P = 0.005) samples using quantitative PCR. On the other hand, higher ARA55 expression was associated with shorter recurrence-free survival (P = 0.02) and overall survival (P = 0.01) in HRPC patients. AR expression was also revealed in all specimens of both prostate cancer and BPH. AR expression level in HRPC samples was significantly higher than that in previously untreated prostate cancer (P = 0.001) and BPH (P = 0.01) samples. CONCLUSIONS: ARA55 may be associated with prostate cancer development and progression. ARA55 expression level in HRPC specimens was significantly lower than that in previously untreated prostate cancer or BPH specimens. On the contrary, our results suggested that a higher ARA55 expression level may result in unfavorable recurrence-free survival and overall survival in HRPC patients. The role of ARA55 may differ between prostate cancer development and the process of progression to a hormone-refractory state. These data not only help to understand the molecular mechanism of prostate cancer development or recurrence, but may also lead to a therapeutic strategy for recurrent prostate cancer that is refractory to hormonal treatment.

Antineoplastic Agents, Hormonal↗

55 kDa nuclear matrix protein (nmt55) mRNA is expressed in human prostate cancer tissue and is associated with the androgen receptor.

Most prostate cancer grows in a hormone-dependent manner. Most patients, however, show hormone-independent growth after several years of hormone therapy. The mechanism of hormone-refractory prostate cancer remains unknown. It is important, therefore, to identify gene(s) related to prostate cancer that are up- or downregulated. We studied differences in gene expression in pairs of prostate cancer and normal prostate tissue utilizing the differential display method. Expression of the identified gene was examined by RT-PCR and real time quantitative PCR (TaqMan-PCR) using 26 pairs of human prostate cancer and normal tissues. We identified a specific upregulated gene encoding a 55 kDa nuclear matrix protein (nmt55) in human prostate cancer. nmt55 gene expression in human prostate cancer tissue was higher (20/26 cases) than that in normal prostate tissue. Moreover, the relationship between nmt55 and androgen receptor (AR) expression showed a positive correlation. In another experiment, transcriptional activity of the prostate specific antigen (PSA) promoter was upregulated by nmt55 in 293 cells. nmt55 showed high expression in prostate cancer compared to normal tissue and its expression showed a positive correlation with AR expression. The PSA promoter was activated by nmt55 expression. These results suggest the possibility that nmt55 expression is related to hormone-dependency or -independence associated with the AR.

Cell Nucleus↗