Treatment with prednisolone of hormone-refractory prostate cancer.

Fifteen patients 60 to 80 years old (a mean of 72 years) with hormone-refractory prostate cancer were treated with low dose prednisolone. All patients had previously undergone hormone therapy. Prostate specific antigen (PSA) values decreased in 11 cases (73%), of which 4 had PSA decreases of 50% or greater. Serum levels of DHEAS significantly decreased at 4 and 8 weeks after treatment (both intervals were p < 0.05 vs pretreatment). Of 8 patients with bone metastasis evaluation, 2 (25%) showed improvement of the lesion. In 5 patients (33%), relief of pain was observed one month after starting prednisolone. The one-year survival rate was 58%. The side effects were mild and manageable in an outpatient clinic.

Metastatic prostate cancer with normal level of serum prostate-specific antigen.

The clinical and pathological features of metastatic prostate cancer with normal level of serum prostate-specific antigen (PSA) were investigated. Four patients with metastatic prostate cancer had serum PSA within the normal range at the diagnosis. All tumors were poorly-differentiated adenocarcinoma. Endocrine therapy was performed as the initial therapy in all patients. Despite subsequently treatment, all cases died of prostate cancer at 2, 8, 9 and 38 months. During disease progression, 3 of 4 patients had elevated serum markers such as carcinoembryonic antigen (CEA), CA19-9, CA15-3, CA125, neuron-specific enolase and pro-gastrin releasing peptide. Immunohistochemical examination of the initial biopsy specimens revealed that 4 and 3 cases were positive for CEA and chromogranin A, respectively. In advanced prostate cancer patients with low PSA level, those markers may aid in the follow up of disease.

Effect of prostatic neuropeptides on migration of prostate cancer cell lines.

BACKGROUND: A previous study by the same authors demonstrated that among various neuropeptides in the prostate, calcitonin gene-related peptide (CGRP) and gastrin-releasing peptide (GRP) increased the invasive capacity of PC-3 prostate cancer cells through enhancement of cell motility, while substance P (SP) inhibited the invasiveness through suppression of motile response. METHODS: The effect of 10 kinds of neuropeptides were investigated, including CGRP, GRP, SP, neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), calcitonin (CT), leucine-enkephalin (L-ENK), methionine-enkephalin (M-ENK), glucagon and parathyroid hormone-related protein (PTH-rP), on the invasion of DU-145 prostate cancer cells through a reconstituted basement membrane (Matrigel) and the haptotactic migration of DU-145, TSU-pr1 and LNCaP prostate cancer cells using a Transwell cell culture chamber assay. RESULTS: It was found that GRP, CGRP and PTH-rP increased the invasive capacity of tumor cells. In contrast, SP, VIP, CT, L-ENK, M-ENK, NPY and glucagon had no significant effect. These three neuropeptides also increased the haptotactic migration of tumor cells to fibronectin. In addition VIP, CGRP and GRP increased the haptotactic migration of LNCaP prostate cancer cells and GRP and PTH-rP increased the migration of TSU-pr1 cells. CONCLUSION: The results indicated that some prostatic neuropeptides increased the invasive potential of prostate cancer cells partially through enhancement of cell motility.

Expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) on prostate cancer cell lines.

Membrane-type metalloproteinase-1 (MT1-MMP) is a transmembrane metalloproteinase, which activates proMMP-2 and expressed on the cell surface in many invasive cancer cells. We investigated the expression of MT1-MMP in prostate cancer cell lines. MT1-MMP protein and mRNA were expressed in PC-3, DU-145 and TSU-pr1 cells (androgen-independent prostate cancer cell lines), but in LNCaP cells (androgen-dependent prostate cancer cell line). MT1-MMP protein was negative and mRNA was low to detect by RT-PCR. Cell lysate of PC-3 cleaved proMMP-2 to the active form. In addition, both hepatocyte growth factor (HGF) and gastrin-releasing peptide (GRP) increased Matrigel invasion and induced the expression of MT1-MMP protein in DU-145 prostate cancer cells. These results suggest that MT1-MMP is indeed the tumor-specific activator of proMMP-2 in androgen-independent prostate cancer cells and plays an important role in the invasive properties of prostate cancer cells.

Effect of chromogranin A (pancreastatin) fragment on invasion of prostate cancer cells.

We investigated the effect of chromogranin A (pancreastatin) fragment on the invasion of PC-3, DU-145 and LNCaP prostate cancer cells through a reconstituted basement membrane (Matrigel) using a Transwell cell culture chamber assay. Chromogranin A fragment increased the invasive capacity of both PC-3 and DU- 145 cells, whereas it had no significant effect of LNCaP cells. Chromogranin A fragment also increased the haptotactic migration of both PC-3 and DU-145 cells to fibronectin. Furthermore chromogranin A fragment increased the fibrinolytic activities of urokinase-type plasminogen activator (u-PA) in fibrin zymograms of both PC-3 and DU-145 cells and the expression of u-PA mRNA of PC-3 cells. However, the growth of these tumor cells was not affected by chromogranin A fragment at any concentrations used in this study. These results indicate that chromogranin A fragment increased the invasive potential of both PC-3 and DU-145 cells probably through enhancement of cell motility and the production of u-PA.

Effect of prostatic neuropeptides on invasion and migration of PC-3 prostate cancer cells.

We investigated the effect of various neuropeptides present in the prostate, including calcitonin gene-related peptide (CGRP), gastrin-releasing peptide (GRP), substance P (SP), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), calcitonin (CT), leucine-enkephalin (L-ENK), glucagon and parathyroid hormone-related protein (PTH-rP), on the invasion of PC-3 prostate cancer cells through a reconstituted basement membrane (Matrigel) using a Transwell cell culture chamber assay. Both CGRP and GRP increased the invasive capacity of tumor cells, whereas SP inhibited it. On the other hand, VIP, CT, L-ENK, NPY, glucagon and PTH-rP had no significant effect. Both CGRP and GRP also increased the haptotactic migration of tumor cells to fibronectin, but SP inhibited it. These three neuropeptides had no effect on either adhesion to fibronectin and laminin or on the gelatinolytic activities of MMP-9 in gelatin zymography, nor did they affect the growth of tumor cells at concentrations used in this study. These results indicate that both GRP and CGRP increased the invasive potential of PC-3 cells probably through enhancement of cell motility, while SP inhibited the invasiveness through suppression of motile response.

[Clinical study on renal pelvic and ureteral tumors].

Thirty five patients with renal pelvic and ureteral tumors were treated at our hospital between 1979 and December 1992. Thirty patients were male and five were female. They ranged in age from 44 to 80 years old (average 67.4 years). The most frequent symptoms were hematuria that was found in 31 cases (24 gross hematuria and 7 microscopic hematuria). Histopathologically, there were 30 transitional cell carcinomas (TCC), 1 squamous cell carcinoma (SCC), 2 TCC > SCC and 1 papillary adenocarcinoma. As to staging, 1 was pTis, 5pTa, 11pT1, 3pT2, 11pT3 and 4pT4. As to grading, 9 were G1, 16 G2 and 9 G3. The incidence of cancerous vessel invasion was noted in 8 of the 29 patients. The 5-year survival rate (Kaplan-Meier's method) was 44.9% for all of the patients. The 5-year survival rate according to staging and according to grading were as follows: 76.7% for low stage (pTis, pTa, pT1, pT2), 24.9% for high stage (pT3, pT4), and 83.3% for G1, 59.9% for G2 and 0% for G3. The 5-year survival rate was 20.8% and 68.7% in the patients with and without vessel invasion, respectively. Grade, stage and cancerous vessel invasion was suggested to be associated with the prognosis in renal pelvic and ureteral tumors.

[Experience of a double Malecot polyurethane intraurethral catheter in patients with dysuria].

We reviewed our experience of using double Malecot polyurethane intraurethral catheters (IUC). Ten patients with dysuria were treated between April 1991 and April 1993. Seven patients with benign prostatic hypertrophy (BPH) were judged as in a high risk group for operation. The three other patients had neurogenic bladder (two had underactive bladder and 1 had overactive bladder). Under local anesthesia, 150 ml of 0.1% Povidone iodine solution was infused into the bladder through a Nelaton catheter. Under guidance by ultrasonography, an IUC was placed into the bladder neck and posterior urethra using the specially designed introduction set. An long-term follow up of the BPH patients, two IUCs were removed for operation and one was exchanged for an indwelling catheter because of deterioration in general condition. In the neurogenic bladder patients, all IUC were removed because of the increase of residual urine, formation of a pseudourethra, or dislocation into the bladder. Side effects were observed in 6 patients such as, urethral bleeding and stone formation in the stent. Erosion and bleeding tendency in the urethral mucosa were shown in the prolonged duration cases. We conclude that a urethral stent is an effective devise for a high risk patient with benign prostatic hypertrophy but we must keep each patient under strict observation for complications during IUC placement.

[Studies of transrectal prostatic ultrasonography on patients with male infertility].

The diagnostic significance of transrectal prostatic ultrasonography for chronic prostatitis and varicocele was evaluated in 380 male infertility patients. Of 20 patients with pyospermia, thought to be mainly caused by chronic prostatitis, 10.0 percent showed heterogeneous echo pattern of the prostate, while 25.0 percent showed capsular irregularity. Since 285 patients with non-infected semen showed similar sonographic findings, it is concluded that prostatic ultrasonography has little value in the diagnosis of chronic prostatitis in infertile patients. Enlarged periprostatic echo-free zone, thought to coincide with the dilatation of the Santrini's plexus, was found in 42.9 and 42.7 percent of patients with chronic prostatitis and varicocele, respectively, in contrast to 34.0 percent of patients without either diseases. Twelve percent of patients with varicocele showed highly enlarged echo-free zone, which was significantly more frequent compared to 5.0 percent in normal patients. Moreover, follow up of 4 patients with varicocele pre- and post-operatively found 2 of them to show a great improvement in the enlargement of the zone. These results suggest that varicocele may cause the dilation of the Santrini's plexus through a venous anastomosis in some patients and transrectal ultrasonography may be a useful tool in detecting small varicoceles in such patients.

Bone marrow scintigraphy in the diagnosis of bone metastasis in prostate cancer.

We investigated bone marrow scintigraphy in 20 patients with prostate cancer to determine the usefulness of this procedure in the diagnosis of bone metastasis. Thirteen of 17 patients whose bone scans revealed hot spots showed accumulation defects in bone marrow scintigrams. Follow-up study and X-ray, computed tomography and/or magnetic resonance imaging findings confirmed the presence of bone metastases in these patients. On the other hand, 4 patients with abnormal bone scans had normal bone marrow scintigrams, and were subsequently demonstrated to have degenerative changes of the spine. Bone marrow scanning therefore appears to be useful in distinguishing metastatic lesions from degenerative changes in cases with suspected bone lesions.

[Primary testicular carcinoid tumor with teratoma: a case report].

We report a case of primary testicular carcinoid with teratoma and review the literature. A 68-year-old man was hospitalized with an asymptomatic left testicular mass. Left radical orchiectomy was performed under a diagnosis of testicular tumor. Histologically, the tumor showed a typical appearance of teratoma with carcinoid components. Barium studies, computed tomographic scan could not demonstrate any other tumor anywhere else. He is now being followed at our clinic without any evidence of recurrence.

[A case of primary aldosteronism due to unilateral multiple adrenal adenomas].

A 64-year-old female with hypertension, hypokalemia visited our hospital. Endocrinological examinations showed a low level of plasma renin activity and high level of plasma aldosterone. Circadian rhythmicity of plasma aldosterone level was recognized. No change in the plasma level of aldosterone was observed after loading of standing and administration of furosemide. Adrenal scintigraphy, adrenal venous aldosterone assay and CT scan revealed two tumors in the left adrenal. The diagnosis of primary aldosteronism by left adrenal tumors was made from the above findings. A left adrenalectomy was performed and pathological findings showed two adenomas, which had no capsule either and were surrounded by normal adrenocortical tissue. Blood pressure normalized after surgery and the plasma levels of aldosterone and plasma renin activity were normalized.