Yukie Takimoto

Histopathological analysis of angiogenic factors in renal cell carcinoma

Aim: The present study was carried out to clarify whether a histopathological analysis of vascular endothelial growth factor (VEGF), transforming growth factor‐β1 (TGF‐β1) and matrix metalloproteinase 2 (MMP‐2) can help predict the outcome of renal cell carcinoma (RCC). We examined the expression of VEGF, TGF‐β1 and MMP‐2 in a large series of RCC with a long follow‐up, based on histopathological factors and survival.

Influence of 5-hydroxytryptamine and the effect of a new serotonin receptor antagonist (sarpogrelate) on detrusor smooth muscle of streptozotocin-induced diabetes mellitus in the rat

Background : We evaluated the changes in the response of detrusor muscle to 5‐hydroxytryptamine (5‐HT; serotonin) and its receptor mechanisms in pathologic bladder of diabetes mellitus rats.

Fluorescence in situ hybridization analysis of c-myc amplification in stage T3N0M0 prostate cancer in Japanese patients

Objective:  Genetic aberration such as the amplification of c‐myc has been commonly found in advanced prostate cancer. The aim of this study was to elucidate chromosome 8 alteration, including a gain and amplification of 8q24 (c‐myc gene), related to the progression and survival in advanced (Stage C) prostate cancer.

Prospective Study of Estramustine Phosphate for Hormone Refractory Prostate Cancer Patients following Androgen Deprivation Therapy

Introduction: Estramustine phosphate (EMP) in combination with other cytotoxic agents has been widely used in clinical trials as an anti-tumor agent for the treatment of hormone-refractory prostate cancer (HRPC). However, few prospective studies have considered the efficacy of EMP monotherapy for HRPC patients following androgen-deprivation therapy (ADT), given the availability of methods to measure prostate-specific antigen (PSA) levels in the serum. We therefore initiated a prospective study to determine whether EMP is efficient for HRPC following ADT using changes in PSA levels as the major endpoint. Methods: After a diagnosis of anti-androgen withdrawal syndrome had been excluded, 34 patients with HRPC who showed an elevated serum PSA level in 3 or more sequential tests following ADT were treated orally with 560 mg/day of EMP. The clinical stage and the median PSA value for inclusion in the study were D2 and 25.9 (range 6.5–540.8) ng/ml, respectively. Treatment was continued until evidence of disease progression reappeared or until severe adverse effects appeared. Results: Of the 34 patients enrolled, 29 were evaluated, while the other 5 (15%) patients were discontinued due to severe gastrointestinal side effects. Seven of the 29 patients (24%) showed a decrease of 50% or greater in serum PSA levels from the initially elevated values, with the median duration of PSA response being 8.0 (range 2.2–18.8) months. Baseline PSA, hemoglobin, alkaline phosphatase, lactate dehydrogenase, performance status, and length of time of initial hormonal treatment did not correlate with the PSA response. With a median follow-up time of 20.0 (range 3.2–45.6) months, the cancer-specific survival rate at 2 years was 83% in the PSA responders and 44% in the non-responders. The PSA response was correlated with cancer-specific survival (p = 0.029). Conclusions: Following ADT one quarter of HRPC patients responded to EMP, with more than 50% of patients showing a decrease in PSA levels and an enhanced survival rate.

Gonadotropin and alkaline phosphatase producing occult gastric carcinoma with widespread metastasis of generalized bone

A case is reported of a small primary occult gastric adenocarcinoma occurring in a 57‐year‐old man revealing widespread metastasis to generalized bone, and associated with high serum level of circulating human chorionic gonadotropin (hCG), carcinoembryonic antigen (CEA), and alkaline phosphatase (ALPase). The primary site of metastatic bone tumor was not clear until autopsy. Microscopic examination of the gastric primary revealed moderately differentiated tubular adenocarcinoma admixed with numerous signet‐ring carcinoma cells without conspicuous trophoblastic differentiation. The elaboration of hCG and intestinal and placental isoenzyme of ALPase by carcinoma cells themselves was confirmed by the indirect immunoperoxidase method. The present case may be interesting because of unusual metastasis and simultaneous production of hCG, CEA, and intestinal and placental ALPase isoenzymes.

Immunohistochemical and Ultrastructural Features of Neuroendocrine Differentiated Carcinomas of the Prostate: An Immunoelectron Microscopic Study

The purpose of this study was to further define the immunohistochemical and ultrastructural characteristics of neuroendocrine (NE) differentiated prostatic carcinomas. Seventy-seven specimens were obtained from prostatic carcinoma tumors during prostatectomy, transurethral resection of prostate or biopsy in 77 prostate cancer patients, and analyzed by immunohistochemical staining for chromogranin A (CgA). Nine of these tumors were also studied by elctron microscopy and 4 were examined by pre-embedding immunoelectron microscopy. CgA-stained cells were detected in 36 tumors (47%). Clinically advanced tumors or tumors with higher histological grades were associated with increased NE differentiation. Three of the tumors studied by electron microscopy contained cells showing unequivocal NE differentiation revealed by the presence of neurosecretory granules, while the poorly NE-differentiated malignant cells contained pleomorphic granules, which were lysosomal-like rather than NE-type granules. Immunoelectron microscopy demonstrated the presence of CgA immunoreactivity on the pleomorphic granules in the poorly differentiated malignant glands. This study suggests that NE-differentiated malignant cells in prostate cancer tissues may induce aggressive behavior in adjacent proliferating neoplastic cells via a paracrine mechanism.

ELECTRON MICROSCOPIC STUDY OF THE PENILE PLAQUES AND ADJACENT CORPORA CAVERNOSA IN PEYRONIE'S DISEASE

Background We conducted ultrastructural studies to clarify the fine structure of penile plaques and adjacent corpora cavernosa, and the causative basis for the process, in Peyronies disease.

Cytoreductive surgery with liver-involved renal cell carcinoma

The purpose of this study was to demonstrate the benefits of cytoreductive surgery for renal cell carcinomas that also involve the liver. Between 1994 and 1997, four patients with renal cell carcinoma with liver involvement were surgically treated with nephrectomy and hepatectomy. Two of them underwent a simultaneous hepatectomy and nephrectomy (group 1), and the remaining two patients underwent a hepatectomy after a nephrectomy and had a diagnosis of postoperative recurrence (group 2). Two patients, one from each group, died of multiple bone metastasis and lung metastasis 30 months and 12 months after the hepatectomy; the second patient from group 1 died 40 months after the first operation due to gastrointestinal hemorrhaging. The second patient from group 2 displayed no evidence of recurrence 18 months after the second surgical procedure. The survival rates for these patients were 66% and 33% at 1 and 3 years, respectively. Autopsy studies revealed that one patient from group 2 had a local recurrence in the liver while the other two patients from group 1 did not. Our results suggested that a progressive approach may therefore be useful for patients demonstrating renal cell carcinoma where there is liver involvement.

[The effect of 5-HT 2 antagonist for urinary frequency symptom on diabetes mellitus patients].

17 cases of patients with diabetes mellitus who had urinary frequency symptom for which anti-cholinergic agents proved ineffective were given Sarpogrelate Hydrochloride (Anplag), a selective 5-HT 2 receptor antagonist. Efficacy was judged using IPSS and QOL scores after 2 weeks medications, these showed that all cases had improved their urinary frequency during the days as well as the night. This was especially true for the QOL score. One time urinary volume markedly increased, but there was no statistical significance after medication in maximum flow rate and residual urine. At the same time, a separate group of 14 mainly BPH cases did not improve entirely. It is believed that reaction in the detrusor muscle with hyperreflexia of diabetes mellitus patients can reach 5-HT, and its reaction is believed to reach via the 5-HT 2 receptor. This paper is a first clinical report of making use of 5-HT 2 antagonist as hyperactive detrusor on diabetes mellitus patients.

Histopathologic analysis of angiogenic factors in localized renal cell carcinoma: The influence of neoadjuvant treatment

This study was conducted in order to clarify whether histopathologic analysis of factor thymidine phosphorylase (TP) and Factor VIII could be a useful predictor of postoperative recurrence in localized renal cell carcinoma. Therefore, the relationship between tumor infiltrated lymphocytes (TIL) and both TP and Factor VIII was studied.