Bicalutamide 80 mg combined with a luteinizing hormone-releasing hormone agonist (LHRH-A) versus LHRH-A monotherapy in advanced prostate cancer: findings from a phase III randomized, double-blind, multicenter trial in Japanese patients.

To compare combination therapy with bicalutamide 80 mg and a luteinizing hormone-releasing hormone agonist (LHRH-A) versus LHRH-A alone in Japanese men with untreated advanced prostate cancer. A total of 205 patients with stage C/D prostate cancer were randomized to either LHRH-A+once-daily oral bicalutamide 80 mg or placebo. Primary study variables have been reported previously. Secondary variables included: time to achieve prostate-specific antigen < or = 4 ng/ml, time-to-treatment failure (TTTF), time-to-disease progression (TTP), overall survival (OS), adverse events and adverse drug reactions. Following combination therapy with bicalutamide 80 mg, there were significant (P<0.001) advantages over LHRH-A alone in terms of TTTF and TTP, but the difference in the interim OS was not statistically significant. First-line combination therapy with bicalutamide 80 mg in Japanese patients with advanced prostate cancer offers significant benefits over LHRH-A alone, with respect to TTTF and TTP. Follow-up for OS continues.

Nucleotide sequence of the thermostable direct hemolysin gene (tdh gene) of Vibrio mimicus and its evolutionary relationship with the tdh genes of Vibrio parahaemolyticus.

The gene encoding a hemolysin similar to the thermostable direct hemolysin (TDH) of Vibrio parahaemolyticus was previously cloned from the chromosome of Vibrio mimicus. The nucleotide sequence of the hemolysin gene was determined in this study. The gene proved to be a variant of the thermostable direct hemolysin gene (tdh gene) and was designated as Vm-tdh because the sequence divergences between the Vm-tdh gene and four tdh genes of V. parahaemolyticus were 2.1-3.0%, while the sequence divergences among the four tdh genes of V. parahaemolyticus ranged between 1.4 and 3.3%. Analysis of these five tdh genes revealed that they evolved from a common ancestor in discrete and understandable order by sporadic base substitutions.

Structural and sequence diversity of the pathogenicity island of uropathogenic Escherichia coli which encodes the USP protein.

A total of 321 uropathogenic Escherichia coli (UPEC) strains and 12 strains of E. coli isolated from stool samples of healthy individuals, which were previously shown to be positive in colony hybridization test using the usp (encoding for the uropathogenic-specific protein) DNA probe, were examined by PCR amplification to determine the size of the usp gene and the pathogenicity island (PI). Three types of size variation were observed for the usp gene and four types for the PI. Sequencing analysis of the PIs from seven representative strains (six UPEC and one from a normal healthy individual) revealed that the usp genes can be classified into two groups, each having different sequences in the 3'-terminal region. The peptides encoded by the three open reading frames (ORFs) downstream of usp had identical 23 amino acid residues in the C-terminal region. The subregion encoding these small ORFs has a mosaic structure constituted of six segments. The positions of these segments vary from strain to strain, and in some strains, two to four segments are deleted. This indicates that rearrangements occur frequently in this region and the mosaic arrangement apparently contributes to the size variation observed in the PCR examination of the usp genes and PIs.

Identification of S, F1C and three PapG fimbrial adhesins in uropathogenic Escherichia coli by polymerase chain reaction.

S and F1C fimbrial adhesins often expressed by uropathogenic Escherichia coli are genetically homologous. A multiply primed polymerase chain reaction (PCR) was developed for discriminating the S (sfa) and F1C (foc) fimbrial operons. A total of 270 uropathogenic E coli strains and 80 fecal isolates were examined. PCR specifically detected the sfa and foc alleles in 105 (93%) of 113 sfa/foc+ strains by DNA hybridization. Furthermore, 87% of sfa+ uropathogenic E. coli simultaneously possessed the genes encoding the class III P fimbrial adhesin (prsG(J96)), alpha-hemolysin and cytotoxic necrotizing factor 1. Statistical analysis showed the class II P fimbrial adhesin (papG(IA2)) and F1C fimbria to be associated with high relative virulence in pyelonephritis and cystitis, respectively. The multiply primed PCR developed should be useful for assessing the contribution of the S and F1C fimbriae in the pathogenesis of urinary tract infections.

Detection of urovirulence factors in Escherichia coli by multiplex polymerase chain reaction.

Primers to amplify the genes encoding the virulence factors of uropathogenic Escherichia coli, such as pilus associated with pyelonephritis (pap), haemolysin (hly), aerobactin (aer) and cytotoxic necrotizing factor 1 (cnf1) genes, were designed. The above primers along with previously reported primers for S fimbriae (sfa) and afimbrial adhesin I (afaI) genes were combined to develop a multiplex polymerase chain reaction (PCR) for detection of the respective virulence factors and for the identification of uropathogenic E. coli. The multiplex PCR to detect pap, sfa, afaI, hly, aer and cnf1 genes was highly specific and the sensitivity was found to be about 5 x 10(3) colony forming units of E. coli per ml. A total of 194 E. coli strains isolated from patients with simple acute cystitis were examined by the multiplex PCR and the results were in complete agreement with that obtained by DNA colony hybridization test. The multiplex PCR developed was, therefore, concluded to be a useful, sensitive and rapid assay system to identify uropathogenic E. coli.

A 3-y prospective study of health-related and disease-specific quality of life in patients with nonmetastatic prostate cancer treated with radical prostatectomy or external beam radiotherapy.

We assessed the longitudinal alteration of the quality of life (QOL) of patients with localized prostate cancer after radical prostatectomy or hormonoradiotherapy during 3-y follow-up. In addition, we examined the impact on QOL of initiation of second treatment after failure of primary treatment. In all, 135 patients with localized prostate cancer who underwent radical retropubic prostatectomy (RP) (N=84) or external beam radiotherapy with neoadjuvant hormone (XRT) (N=51) at our institute and who had a minimum follow-up of 3 y were included in this study. Data were collected prospectively, at baseline, at 3 months after treatment, at 1 y, and annually thereafter. QOL, generic and disease-targeted was evaluated using the European Organization for Research and Treatment of Cancer Prostate Cancer QOL Questionnaire, the Sapporo Medical University Sexual Function Questionnaire, the International Prostate Symptom Index Quality of Life Score and similar questions regarding bowel function. Repeated-measures ANOVA revealed significantly different patterns of alteration in the domains of QOL, with the exception of several domains, between the RP and XRT groups. Rapid decline of sexual function and increase in sexual bothersomeness were followed by slight amelioration throughout follow-up in the RP group, and did not change thereafter in the XRT group. Overall satisfaction with urinary condition significantly improved after treatment and that with bowel condition was stable during follow-up in both of the groups. Failure of primary treatment and initiation of salvage treatment had no impact on QOL. This prospective study revealed longitudinal alteration of QOL status of patients undergoing treatment for localized prostate cancer, but did not yield any conclusions regarding effect of treatment failure and second treatment on QOL due to small sample size. It should be noted that different instruments for assessment of QOL can generate different outcomes.

Transperitoneal laparoscopic adrenalectomy: experience in 100 patients.

Between July 1992 and October 1996, 100 transperitoneal laparoscopic adrenalectomies were performed on 99 patients at our hospital and affiliated hospitals. The clinical diagnoses were primary aldosteronism (41 patients), Cushing's syndrome (15), pre-Cushing's syndrome (6), pheochromocytoma (7; 8 adrenal glands), adrenal cancer (2), nonfunctioning adenoma (22), myelolipoma (3), and complicated adrenal cyst (3). Ninety-seven glands were removed laparoscopically. The mean operative time was 240 +/- 76 (SD) minutes and the mean blood loss 68 +/- 80 mL for the series. The mean blood was 77 +/- 113 mL when the three operations that were converted to open surgery are included. The mean times for the return to a normal diet and unassisted ambulation were 1.3 +/- 0.6 and 1.4 +/- 0.8 days, respectively. The mean duration of the use of analgesics was 1.5 +/- 1.3 days, including the day of surgery. In contrast, in the latest 10 open adrenalectomies done at Kyoto University Hospital, the mean operative time was 186 +/- 53 minutes and the mean blood loss 220 +/- 170 mL. The mean times for return to a normal diet and for unassisted ambulation and the mean duration of the use of analgesics were 1.9 +/- 0.3, 2.9 +/- 1.1, and 2.9 +/- 1.7 days, respectively. Thirty-six operations, excluding one converted to open surgery, performed at Kyoto University Hospital were selected to look at the learning curve for transperitoneal laparoscopic adrenalectomy and evaluated for operative time and blood loss. The mean operative time and mean blood loss in the first 10 procedures performed at Kyoto University Hospital were 256 +/- 63 minutes and 89 +/- 57 mL; however, these values were reduced to 177 +/- 39 minutes and 48 +/- 32 mL in the next 10 procedures at the same hospital. Laparoscopic adrenalectomy via the transperitoneal anterior approach can be equivalent to open adrenalectomy in efficiency with a shorter convalescence.

[Incidentally detected renal cell carcinoma: report of two early small cases].

We report two cases of small renal cell carcinoma, which were incidentally detected by abdominal computed tomography (CT) and ultrasound. Both tumors were less than 15 mm in diameter and low grade, stage I lesions. Incidentally found renal cancer does not always indicate better prognosis. However, in selected patients with small tumors, surgical enucleation may be an acceptable method of treatment even if the contralateral kidney is normal. Renal screening should be a routine part of abdominal ultrasound. In our institution, ultrasound revealed incidental renal cancer in 0.035% of non-urologic patients.

[Spinal anesthesia with isobaric bupivacaine for percutaneous nephro-ureterolithotomy].

The duration of analgesia and the cardiovascular changes during anesthesia of spinal blockade with isobaric bupivacaine were examined in 36 patients between 21 and 75 years old undergoing percutaneous nephro-ureterolithotomy. Injection of 0.25% or 0.5% bupivacaine 3.0-4.0 ml through the L3-4 or L2-3 intervertebral space in the horizontal posture resulted in spread of hypalgesia to T6 in 30 patients and of analgesia to T6 in about a half of the patients. In six patients, another intrathecal injection of 2 ml of bupivacaine was performed because their analgesia level had been under T8. Although the operation took 32-141 min. (mean 77.7 +/- 27.5 min.), there was no case requiring exigent exchanging anesthesia for general anesthesia. The frequencies of the hypotension, bradycardia and nausea in spinal blockade with isobaric bupivacaine were not so different from those of the previous epidural anesthesia in 29 patients undergoing the same operation. Most of the cardiovascular changes in the spinal blockade with isobaric bupivacaine happened within 20-30 min. after intrathecal injection of bupivacaine. Spinal anesthesia with isobaric bupivacaine proved satisfactory for percutaneous nephro-ureterolithotomy.

Prolapsed benign polyp of ureter associated with giant ureteral calculus.

We report a case of a benign fibroepithelial polyp of the lowermost ureter, which prolapsed into the bladder and was associated with a huge, impacted ureteral stone. The polyp was considered to have resulted from chronic irritation of the ureteral mucosa caused by the stone. Review of the literature showed that six out of 74 reported cases had concomitant stones but the polyp was apparently caused by the calculi in only one case.

[A case of adult renal hamartoma resembling congenital mesoblastic nephroma].

A 35-year old man was hospitalized for left flank pain. IVP showed left non-visualizing kidney with multiple renal calculi. Selective renal arteriogram revealed avascular mass in the left upper pole. The upper calyx was irregularly distorted. Left nephrectomy was carried out. Grossly, the upper pole was replaced by whitish, firm and homogeneous tumor, which was 7 X 7 cm in diameter and protruded into the upper calyx. Histologically, the tumor was composed of both epithelial and mesenchymal components. The epithelial elements consisted of cysts and tubules, and the mesenchymal elements of loosely textured fibroblasts and smooth muscle cells. Other elements could not be identified. This case was diagnosed as renal hamartoma histologically resembling congenital mesoblastic nephroma of infancy. Congenital mesoblastic nephroma is rare in adults. Continued maturation may finally transform it either to benign mixed tumor as in our case or fibromatous tumor if stroma matures dominantly.

[Primary localized amyloidosis of the urinary bladder: a case report].

A case of primary localized amyloidosis of the bladder during a twelve-year period is described. The initial symptom was miction pain when she was 43 years old. Cystoscopic examination revealed yellowish elevated lesion with hemorrhage at the right side of the bladder neck. Transurethral resection was performed, but two years later recurrence was found at the trigonum as well as the original site. The two lesions were apart. She remained asymptomatic for the following ten years until she returned to us with bladder symptoms. Cystoscopy showed the lesion was more diffuse and the posterior wall was involved in continuity with the trigonum. Complete transurethral resection was not possible because of generalized bladder involvement. Our case illustrates the clinically benign but slowly progressive nature of amyloidosis of the bladder. Multifocal recurrence is also to be noted. Our current treatment policy is conservative treatment with careful follow-up. She is asymptomatic three months postoperatively.

[National trend of management of benign prostatic hyperplasia in Japan during 1990s: analysis of national health statistics].

To review the contemporary management of benign prostatic hyperplasia (BPH) in Japan during 1990s, we analyzed several nationwide health statistics by the Ministry of Health and Welfare of Japan. The cross-sectional surveys revealed that the estimated total number of patients receiving treatment increased from 202,000 in 1987, to 335,000 and 590,000, respectively, in 1995 and 1998. Approximately 73-80% of patients were men aged 65 years or over and 94-98% 55 years or older. Urologists treated two thirds of the BPH patients. The incidence of prostatectomies remained relatively stable at 50,000/year (3.0-3.8 prostatectomies/1,000 men aged 55 or over). The average hospital stay in 1996 was 24.7 days. The total cost of BPH therapy nearly doubled between 1988 and 1998. The ratio of outpatient to inpatient costs ranged from 1.5 to 2.2 and 60% of the outpatient cost was spent for medical therapy. The total value of the market for medical therapy increased from 30-40 billion yen in 1989 to more than 80 billion yen in 1998. The application of alpha-blockers increased from 243,000 men (70% of all patients) in 1995 to 452,000 (77%) in 1998, whereas the number of patients taking antiandrogens, plant extracts and antispasmodic agents/Ca antagonists (for pollakisuria), respectively, remained relatively stable at 60,000-70,000, 180,000 and 300,000. Because Japan is a rapidly aging society and men aged 55 or older are expected to increase from 15 million in 1995 to 21 million in 2010, cost-effective treatment guidelines for the Japanese BPH patients are needed.

[Two cases of adrenal cysts].

Two cases of adrenal cysts are described. The first case is of bilateral adrenal cysts in a 44-year-old woman. It seems to be the first case of bilateral adrenal cysts in the Japanese literature. The second case is of a left adrenal cyst with sandy calcification in a 71-year-old woman presenting with asymptomatic gross hematuria. Several hormone levels in the cyst fluid were higher than in those in the plasma; cortisol and aldosterone in the first case, and cortisol in the latter. This finding suggests that the hormonal study of cyst fluid obtained by percutaneous needle aspiration under ultrasonic guidance is useful in the differential diagnosis of adrenal cyst from those arising from other organs.

[Ureteral injury in endourological treatment of renal and ureteral calculi].

Percutaneous and transurethral removal of renal and ureteral calculi was performed in 109 cases. Targeted calculi were successfully removed in 105 cases (96.3 per cent), but in five cases combined percutaneous and transurethral procedures were required. Although endourological stone removal resulted in low morbidity rates in many other series, some major complications have also been reported. They include arteriovenous fistula, colo-cutaneous fistula, nephro-duodenal fistula and ureteral avulsion. There were two severe complications in our early experience as well. In one case, a ureteral stenosis was found seven months after two sessions of percutaneous ultrasonic lithotripsy for an upper ureteral stone, and in the other case, a mid-ureteral avulsion was caused by ureteroscopic manipulation. Besides these, we experienced several minor pelvic and ureteral perforations which were easily controlled only by ureteral stent placement. Causes and management of ureteral complications in endourological treatment of renal and ureteral calculi are discussed.

[Endoscopic stone disintegration using the Lithoclast].

We present our experience with a new and unique device for performing intracorporeal lithotripsy known as the Swiss Lithoclast. This simple device uses compressed air to activate a solid probe in a manner of a jackhammer. This device was used to treat 20 patients with stones in the ureter (11), bladder (5) or a Kock pouch (4). The Lithoclast successfully fragmented 90% of the calculi independent of the composition and salvaged 2 failed ESWL treatments. At one month after the procedure, either alone or in combination of with ESWL, 17 of 20 patients became free of stones. There were no complications related to use of the device. We have found the Swiss Lithoclast to be a safe and effective means of performing intracorporeal lithotripsy for urinary calculi.

Transitional cell carcinoma in a pelvic kidney associated with recurrent lung cancer.

We report a case of transitional cell carcinoma of the renal pelvis arising in a pelvic kidney two years after resection of bronchogenic carcinoma. Primary cancer in a pelvic kidney has been rarely described and this is the second reported case of transitional cell carcinoma originating in a pelvic kidney and the first associated with recurrent lung cancer.

[Four cases of urinary lithiasis associated with chronic inflammatory bowel disease].

We report 4 cases of urinary lithiasis associated with chronic inflammatory bowel disease. All cases were surgically treated and the mode of operation was total colectomy in two cases, ileal resection (1 m) in 1 case and total colectomy and ileal resection (1 m) in 1 case. The composition of the stone was uric acid in 2 cases treated with total colectomy and calcium oxalate in the other 2 cases treated with ileal resection. Low urine volume was observed in 3 cases and acid urine in all cases. Hypocitruria was observed in 3 cases. Two cases with ileal resection showed enteric hyperoxaruia and increased urinary excretion of oxalate was observed on the oxalate loading test.

[Postoperative complications of self-catheterizable continent urinary diversions (Kock, Indiana, and appendiceal Mainz pouch) and patient care].

A self-catheterizable continent urinary reservoir has become one of the major options for urinary diversion in patients with invasive bladder cancer or other pelvic malignancies. We performed the Kock pouch, the Indiana pouch and the appendiceal Mainz pouch in 124, 51 and 4 patients with the mean followup periods of 50, 33, and 10 months, respectively. In the Kock pouch, the efferent and afferent nipple valve malfunction was seen in 16.7 and 21.3 percent each, requiring repair surgery, such as fixation of the efferent nipple to the pouch wall, reconstruction of an isoperistaltic nipple valve in the former, and removal of the Dacron fabric collar or re-anastomosis of the ureter to the pouch using LeDuc technique in the latter. In the Indiana pouch, stomal stenosis, an hourglass-like pouch deformity, difficult catheterization occurred in 3, 2 and 2 patients, respectively. Among the 4 patients with the appendiceal Mainz pouch, there were no major late postoperative complications except for mild stenosis of the conduit, handled with bougienage. As a whole, surgical revisions, related to urinary diversion, was done in 20.3, 10.6, 0 percent in the Kock, Indiana, Mainz pouch patients, respectively. Stone formation, mostly multiple and recurrent, occurred in 27.8, 6.4, 0 percent in the Kock, Indiana, Mainz pouch, respectively. Most of the stones were removed endoscopically via a stoma or by percutaneous approach. Acidosis was seen in 3 patients in both the Kock and Indiana pouch, and 3 patients with the Kock pouch suffered from symptomatic choleithiasis. At the time of the latest observation, continence was achieved in 90.2, 93.0, and 100 percent, whereas excretory urograms showed normal collecting systems in 64.5, 90.4, and 100 percent in the Kock, Indiana, and Mainz pouch, respectively. In conclusion, the Kock pouch, performed by an original method using unabsorbable polyester fabric collars and metallic staples, has an intolerably high rate of late complications, and either the modified Indiana pouch with ileal patch or the appendiceal Mainz pouch using the umbilicus as a stoma is recommended for a self-catheterization continent urinary diversion.

[A case of incidental renal leiomyosarcoma].

A 68-year-old man visited his home doctor with the chief complaint of left flank pain. Abdominal ultrasonography revealed left hydronephrosis and space occupying lesion in the right kidney. He was referred to our hospital because of suspected left ureteral stone and for further examination. Drip infusion pyelography revealed a left ureteral stone and retrograde pyelography showed extrinsic compression and deformation of the right pyelogram. A computed tomography showed a heterogeneous solid mass, 7 x 4 cm in size, compressing the pelvicocalyceal system and growing out of the kidney. Right radical nephrectomy was performed under the diagnosis of renal cell carcinoma. The pathological diagnosis was leiomyosarcoma. Seventy-five cases of renal leiomyosarcoma have been reported in the Japanese literature and this is the third case as an incidental tumor. Because of the absence of the characteristic diagnostic signs, this malignant tumor can present diagnostic difficulty. The diagnostic problems and clinical features of renal leiomyosarcoma are discussed.