Endocrine response to a single injection of goserelin 3.6 mg or leuprolide 3.75 mg in men with prostate cancer.

Hormonal responses were assessed in men with prostate cancer (T2-4, Nx, Mx) who were randomized to receive either a single injection of goserelin 3.6 mg or leuprolide 3.75 mg. Testosterone increased over the first week, with a significantly higher mean rate of change of total testosterone (day 3) and free testosterone (days 3 and 7) with leuprolide. Following the initial rise in luteinizing hormone (LH), the rate of decrease in LH levels was significantly greater with goserelin by day 28. There are significant differences in endocrine response to goserelin and leuprolide in the 4 weeks following administration.

Reticulocyte hemoglobin content as a marker of iron status in patients receiving maintenance hemodialysis.

Background. Patients with renal anemia who show a poor response to erythropoietin might have iron insufficiency. Reticulocyte hemoglobin content (CHr) was measured in hemodialysis patients, and its potential as a marker for iron status was assessed by comparing CHr with ordinary markers. Methods. Ninety-one patients receiving maintenance hemodialysis were enrolled. Venous sampling was performed twice, at a 3-month interval. During the interval, none of the patients received any iron agent and there was no alteration in their erythropoietin doses. CHr was measured with an automated blood cell counter. Simultaneously, ordinary markers for iron status, such as hematocrit (Ht), mean hemoglobin content (CH), serum iron (Fe), ferritin (Fr), and transferrin saturation (TSAT), were measured. CHr was compared with these markers. Results. CHr randed from 24.1 to 34.7 pg, with a mean of 31.0 pg. CHr correlated with CH (P < 0.001), Fr (P < 0.01), Fe (P < 0.001), and TSAT (P < 0.001), but not with Ht. When patients were divided into two groups according to the CHr : CH ratio (CHr : CH ≧ 1 and CHr : CH < 1), there was no difference in any parameter between the two groups in the first measurement. In the second measurement, done after a 3-month interval, patients with CHr : CH ≧ 1 showed significantly higher values for CHr (P < 0.001), CH (P < 0.01), Fe (P < 0.05), and TSAT (P < 0.05) than patients with CHr : CH < 1. Conclusions. It was suggested that the CHr : CH ratio would predict changes in the state of iron supply. CHr might be a potential marker for monitoring renal anemia.

Renal arteriovenous fistula developing after tumor enucleation using a microwave tissue coagulator.

With the increase in detection of incidental renal cell carcinoma, nephron-sparing surgery for small renal cell carcinomas is now recognized as one of the surgical options. We report a case of renal arteriovenous fistula developing after non-ischemic tumor enucleation of a small renal cell carcinoma using a microwave tissue coagulator. A 50-year-old Japanese man presented with right flank pain and gross hematuria. The patient had undergone non-ischemic tumor enucleation for right renal cell carcinoma, 2 cm in diameter, 1 month previously. Doppler ultrasound revealed the formation of an arteriovenous fistula at the enucleated portion. Transcatheter super-selective occlusion of the feeding artery was successfully performed with two metallic coils. The patient has been followed up with no sign of recanalization of the fistula. In this case, the tumor was located close to the renal hilus with thick arterial branches around the tumor. Additional microwave coagulations against arterial bleeding from the cutting surface might have been the cause of the fistula formation of this case. Non-ischemic tumor enucleation using a microwave tissue coagulator is a relatively easy and secure nephron-sparing surgical procedure. Excessive coagulation, however, should be avoided, since it might be the cause of unexpected postoperative vascular complications.

[Screening methods in the detection of bladder cancer: comparison of nuclear matrix protein-22, bladder tumor antigen and cytological examinations].

We evaluated the utility of urinary parameters (Nuclear Matrix Protein-22: NMP-22, Bladder Tumor Antigen: BTA, and cytological examinations) for the diagnosis or post-therapeutic monitoring of bladder cancer. Thirty one tumor-bearing cases including 19 fresh cases and 40 tumor-free cases, were subjects of this study. Using identical voided urine samples, NMP-22, BTA and urinary cytology were examined. The mean values of NMP-22 (cut-off value is 12 U/ml) was 100.5 +/- 26.5 U/ml in the tumor-bearing group and 21.9 +/- 7.8 U/ml in the tumor-free group (p < 0.05): Sensitivity was 74.2%, and specificity was 67.5%. Sensitivity of BTA was 58.1%, and specificity was 97.5%. Only five cases were judged positive by urinary cytology: 16.1% in sensitivity and 100% in specificity. Thus, NMP-22 and BTA were more sensitive than urinary cytology. In conclusion, the new urinary parameters, NMP-22 and BTA, would be less invasive and useful as tumor markers of bladder cancer. NMP-22 seems suitable for screening before the diagnosis and BTA for the post-therapeutic follow-up study.

[Prostatic cancer developing after transurethral resection of the prostate for benign prostatic hyperplasia].

From January 1993 to June 1998, 319 cases were histopathologically diagnosed as prostatic cancer. In 7 of the 319 cases (2.2%) transurethral resection of the prostate (TUR-P) had been performed and a diagnosis of benign prostatic hyperplasia had been made with the resected specimens. The interval between TUR-P and the diagnosis of prostatic cancer ranged from 22 months to 15 years. All the cases showed an elevation of the prostate specific antigen (PSA) value (6.4-399 ng/ml, Tandem-R: RIA) at the time of cancer diagnosis. In 2 cases, PSA was measured in cancer screening. The clinical stage was stage B1 in 2 cases, stage B2 in 2 and D2 in 3. Only one case had been regularly followed-up after TUR-P, in which cancer was diagnosed by needle biopsy 22 months after TUR-P, because of the sustained high PSA values. Since most of such patients have an advanced stage of prostate cancer, it is of importance to have periodical follow-up examinations after TUR-P. The measurement of PSA appears the most reliable means in this way.

[Screening for prostatic diseases in one-day total health check-up by using prostate specific antigen, international prostate symptom score and QOL index].

We preliminarily studied screening for prostatic diseases in one-day total health check-up by employing prostate specific antigen (PSA), international prostate symptom score (IPSS) and quality of life (QOL) index. From January 6 to March 31, 1998, a total of 390 men were included in this study, whose age ranged from 50 to 78 years with the mean of 57.5 years. The questionnaires, IPSS and QOL index, were mailed to the participants in advance. PSA (IMx: Dainapack) was measured at the end of the health check-up and the results of tests were explained on the same day. Participants who showed more than 8 points in IPSS, more than 4 points in QOL index and/or more than 4.1 ng/ml in PSA were given a referral to urologists of corresponding hospitals for further examination. A total of 116 men (29.7%) were judged to need thorough examination. Among 106 men who were referred to urologists, only 34 (32.1%) had visited the urologists by the end of July 1998. Two men (0.51% in all participants) were diagnosed with prostate cancer, 10 received some pharmacotherapy, and 2 underwent transurethral resection of prostate. The results indicate that screening for prostatic diseases in total health check-up is useful, even in an institute without staff urologists, in close association with urologists.

A prospective randomized multicenter study of chlormadinone acetate versus flutamide in total androgen blockade for prostate cancer.

BACKGROUND: A randomized multicenter study was conducted to investigate the efficacy of total androgen blockade (TAB) for patients with previously untreated prostate cancer using the steroidal anti-androgen chlormadinone acetate (CMA) and the non-steroidal anti-androgen flutamide. We also compared the liver dysfunction in these two arms. METHODS: From November 1995 to October 1997, 71 patients were registered into this study and 70 of them were eligible. RESULTS: There was no significant difference in the efficacy of TAB between CMA and flutamide at 24 weeks. The testosterone and prostate-specific antigen (PSA) levels in patients administered flutamide (Group II) increased significantly 3 days after the first dose of LH-RH analog, whereas no such increase was observed in patients administered CMA (Group I), indicating that CMA prevented the flare-up. Parameters of liver function, serum GOT and GPT levels, which were normal at the baseline, became abnormal in 30.0% and 35.3%, respectively, of patients in Group II. These figures were significantly higher than the corresponding figures of 6.3% and 12.5%, respectively, in Group I. When the degree of change in each of these parameters was analyzed, both GOT and GPT levels showed a significantly greater increase in Group II than in Group I. CONCLUSION: These results indicate that attention must be paid to changes in liver function during the administration of flutamide in patients with prostate cancer even if their baseline liver function is normal. It is also suggested that CMA may be better tolerated from the viewpoint of the drug effects on liver function.

Urachal tuberculosis.

BACKGROUND: We report on an extremely rare case of urachal tuberculosis that was confirmed using a polymerase chain reaction test of paraffin-embedded material. METHODS/RESULTS: A 62-year-old man presented with pollakiuria. With a diagnosis of urachal abscess, the patient underwent en bloc resection of the cystic mass. A bacterial culture test of the content showed no organism. The histopathologic findings suggested urachal tuberculosis. The AMPLICOR polymerase chain reaction test by using paraffin-embedded sections revealed the existence of Mycobacterium tuberculosis in the resected tissue. The only positive finding in systemic screening examinations for tuberculosis was old tuberculosis scars in the upper right lung. It was supposed that hematogeneous spreading from the lung lesion may result in urachal tuberculosis after a long latent period. CONCLUSIONS: Although urachal tuberculosis is an extremely rare condition, tuberculosis must always be kept in mind when observing any infectious diseases.

Diagnostic usefulness of endorectal magnetic resonance imaging with dynamic contrast-enhancement in patients with localized prostate cancer: mapping studies with biopsy specimens.

BACKGROUND: New diagnostic criteria for dynamic magnetic resonance (MR) imaging in prostate cancer are presented. The diagnostic usefulness of endorectal MR imaging with dynamic contrast-enhancement in localized prostate cancer and the validity of these criteria were evaluated. METHODS: Eighteen untreated patients who were suspected of localized prostate cancer were included in the study. They received endorectal dynamic MR imaging before systematic sextant needle biopsy. First. a mapping study with the findings of MR images and histopathology of biopsy specimens was performed in eight patients out of 18 to compare the difference in T2-weighted images with the endorectal coil and the body coil in the same individuals. Second, another mapping study was performed in all 18 patients by analyzing the findings of endorectal dynamic MR images. For the diagnosis of prostate cancer in MR imaging, we offered diagnostic criteria from our experience in addition to those in plain T2-weighted images from the literature. RESULTS: The overall diagnostic rates of endorectal dynamic MR imaging were 88.9% in accuracy, 100% in sensitivity, and 81.8% in specificity. In the comparison of the endorectal and body coils in T2-weighted images in eight patients, there was no difference in the diagnostic rates except for one more histopathologic false positive portion in endorectal MR imaging. In the second mapping study in 18 patients, the diagnostic rates were 92.6% in accuracy, 88.9% in sensitivity and 93.3% in specificity. Endorectal dynamic imaging raised the diagnostic sensitivity from 77.8 to 88.9%. CONCLUSION: The data demonstrated the validity of this diagnostic criteria and the diagnostic usefulness of endorectal dynamic MR imaging in localized prostate cancer.

[Intra-arterial chemotherapy for invasive bladder cancer].

The present investigation was conducted to examine the effects of intra-arterial chemotherapy (IAC) for patients with invasive bladder cancer. A total of 37 patients were treated with IAC at Nara Medical University and its affiliated hospitals between January, 1993 and August, 1997. There were 27 patients in the poor risk group. The remaining 10 patients underwent anti-tumor IAC. Thirty of the 37 patients received chemotherapeutic agents via a reservoir, and the remaining 7 patients received a one-shot injection of agents followed by transcatheter arterial embolization (TAE). In the reservoir group, there were 18 patients who received IAC in combination with radiation therapy. As a result, reduction of tumor size was noted in 53%, and the 3-year cause-specific survival rate was 54% in all cases. There was a significant difference in the 3-year survival rate between the radiation-treated group and the group without radiation. The adverse events included anemia, leukopenia, thrombocytopenia and gastrointestinal symptoms, but none of them were severe. The results of the present study indicate that IAC is useful in the treatment of invasive bladder cancer for poor risk patients.

Sequential changes of urinary pyridinoline and deoxypyridinoline as markers of metastatic bone tumor in patients with prostate cancer: a preliminary study.

Urinary concentration of pyridinoline and deoxypyridinoline, novel markers of bone resorption, was measured serially in patients with prostate cancer as markers of metastatic bone tumor. In 11 patients, five without bone metastasis and six with bone metastasis, pyridinoline and deoxypyridinoline were serially monitored for between 6 and 24 months. All patients received some hormonal therapy with or without radical prostatectomy. Pyridinoline and deoxypyridinoline were measured by ion-paired high-performance liquid chromatography and were adjusted according to urinary creatinine concentration. The sequential changes of pyridinoline and deoxypyridinoline were compared with those of prostatic specific antigen and alkaline phosphatase as well as with the findings of bone scintigrams. During the observation periods, no metastatic bone lesion developed and no significant changes in pyridinoline and deoxypyridinoline occurred in the five patients without bone metastasis. In the six patients with bone metastasis, the levels of prostatic-specific antigen showed relatively rapid decreases after starting therapy. In contrast, the levels of pyridinoline, deoxypyridinoline and alkaline phosphatase showed transient increases followed by gradual decreases in most cases. Correlations were observed between the changes of pyridinoline and deoxypyridinoline and the findings of bone scintigrams. The data suggest that serial monitoring of pyridinoline and deoxypyridinoline could be clinically useful as markers of metastatic bone tumors and may allow less frequent bone scintigrams during patient followup.

A histopathological mapping study of the urinary bladder tumors induced by N-butyl-N-(4-hydroxybutyl)nitrosamine in dogs.

Bladder tumors were induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in five Beagles and four mongrel dogs. The tumors were observed for long periods and the tumor progression was traced using histopathological mapping. The results indicated (1) that low-dose BBN over a long period induced multiple low-grade (G1-2) and low-stage (pTa-1) papillary tumors, resembling superficial bladder cancer in humans; (2) that high-dose BBN over a short period induced high-grade (G2-3) and high-stage (pT3b) nonpapillary tumors and carcinoma in situ (CIS) resembling invasive cancer and CIS in humans; (3) that beagle dogs required longer periods and higher total doses of BBN as compared with mongrel dogs; (4) that the tumors induced by low-dose BBN in beagles were observed without BBN as long as the animals lived, and neither increasing numbers of tumors nor malignant features such as deep infiltration and metastasis was observed; and (5) that low-dose BBN seems to induce mild dysplasia, which is followed by Brunn's nest-like proliferation in the lamina propria and nodular change, eventually leading to the development of papillary noninvasive transitional cell carcinoma (TCC); and that high-dose BBN seems to induce severe dysplasia which leads to CIS and nonpapillary invasive TCC. These results may contribute to clarifying the natural history of human bladder cancer.

[Clinical study of testicular cancer].

Since April 1986, a prospective clinical trial for testicular cancer has been underway by our Nara Uro-Oncology Research Group. One hundred and forty-eight cases of germ cell tumor were entered into this study between April, 1986 and August, 1995. They included 99 cases (66.9%) of seminoma and 49 cases (33.1%) of non-seminomatous germ cell tumor (NSGCT). The mean age of seminoma cases (39.7 yrs) was higher than that (30.2 yrs) of NSGCT cases. One hundred and twenty-three cases were treated according to our protocol. In the treatment group, one patient with stage I seminoma died of other diseases and one patient each with stage II and stage III seminoma died of cancer. Three patients with stage III NSGCT died of cancer. The 5-year survival rate was 100% for stage I seminoma, and stage I and stage II NSGCT, 75.0% for stage II seminoma, 0% for stage III seminoma and 66.7% for stage III NSGCT. These findings suggest that new treatment modalities should be introduced into our protocol in the future.

[Serum and urinary pyridinium cross-links in patients with predialysis chronic renal failure].

The concentrations of pyridinoline (Pyr), a novel marker of bone resorption, were simultaneously measured in both serum and urine samples by ion-paired high-performance liquid chromatography in 27 patients with predialysis chronic renal failure. The patients consisted of 19 males and 8 females, whose creatinine clearance (Ccr) ranged from 2.5 to 47.6 ml/min. The influence of residual renal function on serum Pyr and the clinical significance of serum and urinary Pyr were analyzed in patients with predialysis chronic renal failure. There were significant correlations between serum Pyr and serum Cr (r = 0.76) and between Pyr clearance and Ccr (r = 0.70). In addition, significant correlations were observed serum and urinary Pyr (r = 0.64) and between both serum and urinary Pyr and HS-PTH (r = 0.96 and r = 0.61, respectively) and osteocalcin (r = 0.80 and r = 0.73, respectively). However, serum bone alkaline phosphatase isoenzyme (ALP3) was correlated with neither serum nor urinary Pyr. There was no correlation between the ratio of serum Pyr/serum Cr and the metabolic bone markers (HS-PTH, osteocalcin and ALP3). There was a correlation between Ccr and urinary Pyr, although it was statistically significant (p < 0.1). These date led to the following conclusions: (1) serum Pyr in patients with oredialysis chronic renal failure is influenced by reduced renal function and (2) urinary pyr shows a state of bone resorption when an adegvafe level of renal function is maintained. This suggests that patients with an advanced stage of renal osteodystrophy are included among cases of predialysis chronic renal failure.

In situ non-ischemic enucleation of multilocular cystic renal cell carcinoma using a microwave coagulator.

A case of multilocular cystic renal cell carcinoma is reported, in which nephron-sparing surgery was done using microwave tissue coagulation. A 37-year-old man was referred to our outpatient clinic for a multilocular cystic tumor, 4.5 cm in diameter, in the middle-lower portion of the right kidney, which was detected by ultrasound during a health checkup. The patient had been found to have the same cystic mass on a CT done during another health checkup 1.5 years before. The tumor showed no growth during the 1.5-year period. With a diagnosis of multilocular cystic renal cell carcinoma, T2N0M0, in situ non-ischemic tumor enucleation was done using a microwave tissue coagulator (Microtaze, Heiwa Electronics Industry Inc., Tokyo). Operation time was 150 minutes and blood loss was 135 cc. The histological diagnosis was renal cell carcinoma, T2N0M0V0, cystic type, clear cell subtype, grade 1. Diagnostic imaging done postoperatively showed no sign of damage to renal function. In this report, the characteristics of multilocular cystic renal carcinoma are reviewed from the literature, and the advantages of nephron-sparing surgery for this type of renal tumor are discussed. In addition, an operative technique of tumor enucleation used in this case and the characteristics of Microtaze are introduced.

[Measurement and clinical significance of serum concentrations of pyridinium cross-links in patients with renal osteodystrophy].

Serum concentration of the pyridinium cross-links, pyridinoline (Pyr) and deoxypyridinoline (Dpyr), which are markers of bone resorption, was measured by high-performance liquid chromatography in 56 patients on maintenance hemodialysis. The following analyses were conducted: 1) correlation with known markers of bone metabolism, 2) correlation with findings on bone changes on plain X-ray film, 3) elimination rates by hemodialysis, and 4) increment per day in pyridinoline after hemodialysis (delta Pyr/day). There was a very close correlation found between serum Pyr and Dpyr (r = 0.861). Both serum Pyr and Dpyr showed correlations with known markers of bone metabolism: C-PTH (r = 0.806 and r = 0.747, respectively), M-PTH (r = 0.766 and r = 0.749), osteocalcin (r = 0.717 and r = 0.693), Alp-3 (r = 0.523 and r = 0.441) and tartrateresistant acid phosphatase (r = 0.549 and r = 0.548). In addition, a correlation between the duration of hemodialysis and serum Pyr and Dpyr was observed (r = 0.426 and r = 0.318, respectively). When comparing the mean values of serum Pyr or Dpyr in three groups of patients divided according to bone changes seen on plain X-ray film, there were statistically significant differences between the group without bone changes and the remaining two groups with some bone changes (p < 0.05). A mean of 45.3% of serum Pyr was removed by hemodialysis. The serum Pyr level returned almost to the original concentration by the following hemodialysis. delta Pyr/day showed a close correlation with C-PTH (r = 0.656).(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of patent urachus].

A case of congenital patent urachus is reported. A 12-month-old boy was referred to our outpatient clinic with the complaint of watery discharge from the navel. A cystography revealed the communication between the dome of the urinary bladder and the umbilicus. Excretion from the umbilicus of indigocarmine solution instilled into the urinary bladder was recognized. There were no complicated abnormalities in other organs. The patient underwent radical operation. Herein, we collected 164 cases of urachal disorders reported in Japan and reviewed the incidence, clinical symptoms, diagnosis and treatment. The classifications of the disease were briefly discussed.

Sequential changes in stem cell markers in peripheral blood and leukapheresis samples after injections of recombinant human granulocyte colony-stimulating factor in patients with urogenital malignant solid tumors: a preliminary study.

In order to evaluate the mobilization effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on peripheral blood stem cells (PBSCs), rhG-CSF was given to patients with urogenital malignancy before chemotherapy. Markers for the stem cells, such as colony forming unit-granulocyte/macrophage (CFU-GM) and burst forming unit-erythrocyte (BFU-E), were sequentially monitored in peripheral blood and leukapheresis samples. Five patients, including a 13-year-old boy, were given 5 micrograms/kg rhG-CSF subcutaneously: the pediatric case for four consecutive days and the adult cases for six consecutive days (53-72 years of age). None of the patients had received chemotherapy within the four weeks prior to the start of the rhG-CSF series. PBSC collections were performed on the fifth day in the pediatric case and on the fifth and seventh days in the adult cases. Progenitor cells were monitored by methyl-cellulose cell culture techniques. CFU-GM on day 5 of the rhG-CSF series in peripheral blood increased 14- to 53-fold compared with samples taken immediately before the series. CFU-GM in the leukapheresis products on day 5 was greatest (70 x 10(3)/kg) in the pediatric case and least (14 x 10(3)/kg) in the oldest patient's case. The totals of the CFU-GM collected by two phereses in the adult cases were 21-73 x 10(3)/kg and the totals of CD34 positive cells were 0.6 to 1.4 x 10(6)/kg. The data suggest rhG-CSF to induce sufficient PBSCs for bone marrow rescue into the peripheral blood without any preceding chemotherapy. The patient's age may, however, be a contributory factor in using this method.

[Quantitative flow-cytometric analysis of CD34-positive stem cells in peripheral blood stem cell harvests].

The percentage of CD34-positive cells (the CD34-positive rate) in peripheral blood stem cell harvests (PBSCH) was determined using two color flow cytometric methods, i.e., representation in a histogram (the histogram method) and the two-dimensional side scatter-fluorescence representation (the SSC-FL method). For all samples examined, the CD34-positive rate obtained using the histogram method was higher than that obtained using the SSC-FL method. This finding was probably due to the fact that some monocytes non-specifically reacted with anti-CD34 monoclonal antibody, and the histogram method could not distinguish these non-specifically stained cells from CD34-positive precursor cells. On the other hand, the SSC-FL method seemed to yield a more accurate measurement of the percentage of CD34-positive cells in PBSCH samples. Based on this finding, it is recommended that the histogram method, which is currently used at most commercial laboratories, be reviewed in favor of the SSC-FL method when the CD34-positive cell rate of PBSCH is to be determined.

[A case of retroperitoneal extramedullary plasmacytoma].

Extramedullary plasmacytoma (EMP) is a very rare disease and mainly arises in the head and neck area. We herein reported a case of EMP arising in the retroperitoneal space. A 46-year-old man was referred to our outpatient clinic in November 1989 with the complaint of flank pain on the left side. Radiological examinations showed a tumor formation in the retroperitoneal space, which involved the left kidney, spleen and pancreas. Immunoelectrophoresis showed an elevation of serum IgG level and a spike of M-protein was detected in the serum protein electrophoresis. No bone lesions were detected, and bone marrow aspiration showed no abnormal cells. US-guided needle biopsy of the tumor led to the histological diagnosis as plasmacytoma of the IgG-kappa type. Following three cycles of preoperative chemotherapy (a THP-COP regimen), which resulted in a size reduction of the tumor by 40%, extensive resection of the tumor including extirpation of the left kidney, spleen, and tail of pancreas was performed. Because of tumor extension into the posterior wall of the stomach, however, the surgery resulted in incomplete resection. A total of 11 cycles of postoperative chemotherapy (THP-COP) was performed periodically for the residual tumor in the stomach. Rapid tumor spreading in addition to re-elevation of the serum IgG level, however, developed after the 11th postoperative chemotherapy, which extensively involved the stomach and intestines. The patient died of the disease 33 months after the initiation of treatment.