Covering of the terminal ureter with de-serosalized muscle layer of the ileum for antireflux ureteroileostomy: an experimental study in dogs and a preliminary clinical trial.

We demonstrated a new operative technique for antireflux ureteroileostomy in dogs. The severed ureter was reimplanted into the isolated ileum. Ten terminal ureters were covered with a 2 x 2 cm2 section of de-serosalized ileal wall after direct ureteroileostomy, and another six terminal ureters were covered with a 2 x 2 cm2 section of non-de-serosalized full-thickness ileal wall. Thirteen ureters were directly anastomosed to the ileum without any additional procedures. The bladder was augmented by the detubularized ileum with the ureter. Postoperative evaluations on ureteral stenosis and reflux were performed monthly for 3 months. The ureters covered with the de-serosalized ileal wall prevented ureteral reflux even when the intravesical pressure climbed as high as 100 cm H2O. Although two of these ten ureters demonstrated strictures at the precise site of direct ureteroileostomy, the sections of the ureters covered with the de-serosalized ileal wall were opened and did not collapse. In the resected specimens, the terminal ureters were found in the intramural part of the ileum. The ureters covered with the full-thickness of ileal wall did not prevent reflux. Our method of covering the terminal ureter with the de-serosalized ileal wall worked well as an antireflux mechanism, and the intramural ureter did not cause ureteral stricture. After this animal experiment, we introduced this antireflux mechanism clinically.

Primary signet ring cell carcinoma of female urethra.

A 69-year-old woman presented with difficulty in urination and bloody fluid discharge from the urethra. Based upon a diagnosis of primary urethral carcinoma, she underwent total cysto-urethrectomy and hysterectomy with pelvic lymph node dissection and urinary diversion of ileal conduit. Microscopically, the tumor was composed of mucinous adenocarcinoma and signet ring cell carcinoma. There was no recurrence 17 months after the surgery.

A technique for resection of small bladder tumors using a flexible cystoscope on an outpatient basis: bladder tumor resection with newly designed hot cup forceps.

PURPOSE: We describe a technique for resecting small papillary superficial bladder tumors using a new device and flexible cystoscope. MATERIALS AND METHODS: In a 79-year-old man 3 small recurrent papillary bladder tumors were resected transurethrally on an outpatient basis. The procedure was performed using a flexible cystoscope and a newly designed type of cup forceps with the patient under topical anesthesia. No urethral catheter remained indwelling after surgery and the patient was discharged home the same day. RESULTS: Bladder tumor resection using this technique was tolerable to the patient and postoperative bladder hemorrhage was not noted. Resected specimens were adequate for pathological tumor evaluation, which revealed grade 1 stage Ta superficial transitional cell carcinoma of the bladder. CONCLUSIONS: This easy technique seems to be tolerated well by the patient. Resected specimens should be adequate for evaluating the pathological grade and depth of stage Ta or T1 superficial bladder cancer. This technique may be an alternative to standard transurethral resection for removing small recurrent bladder lesions in select patients who prefer outpatient management of bladder tumors.

Role of thymidine phosphorylase in biomodulation of fluoropyrimidines.

Thymidine phosphorylase (TP) is a key enzyme in the activating pathway of 5'DFUR and capecitabine. On the other hand, TP is identical to platelet-derived endothelial cell growth factor (PD-ECGF) which is known to be an angiogenic factor. Recent studies show TP expression is increased in various malignancies compared with the surrounding normal tissues. These reports demonstrate that elevated TP expression indicates a predisposition for aggressive disease and/or poor prognosis. Therefore, it is a reasonable strategy to target TP in cancer treatment by using fluoropyrimidines including 5-fluorouracil (5FU), 5'DFUR and capecitabine. TP-mediated biomodulation of fluoropyrimidines to enhance their anti-tumor effects has been investigated. TP up-regulators including cytokines, anti-tumor drugs and X-ray irradiation significantly increase cytotoxicity of fluoropyrimidines. Also, transfection of TP cDNA significantly enhances cytotoxicity of fluoropyrimidines. Biomodulation of fluoropyrimidines is clinically successful in treating some malignancies. We report a review on roles of TP in biomodulation of fluoropyrimidines.

[Serum CA19-9 levels in testicular germ cell tumor patients].

This study was designed to examine whether measurement of serum CA19-9 was useful in testicular germ cell tumor patients. We analyzed the clinical courses of 55 testicular germ cell tumor cases diagnosed after high orchiectomy. The patients in this study consisted of 33 seminomas and 22 non-seminomatous germ cell tumors (NSGCT), and their mean age was 32.7 +/- 12.7 years (mean +/- SD). The mean follow-up period after the operation was 33.7 months. The positive rate of the pre-treatment serum CA19-9 level was 16.4% (3.0% in seminomas versus 36.4% in NSGCT, p = 0.0017). The pre-treatment serum CA19-9 levels in NSGCT patients were significantly higher than those in seminoma patients (46.6 +/- 50.0 U/ml versus 10.6 +/- 9.6 U/ml, p = 0.0008). We divided the patients into two groups according to the detailed histological types, and found that the serum CA19-9 levels in the patients with embryonal carcinoma (EC) were significantly higher than in those without EC (p = 0.0160), and the levels in those with yolk sac tumor (YS) were higher than in those without YS (p = 0.0099). Moreover, the levels in those with either EC or YS were significantly higher than in those with neither EC nor YS (p = 0.0004). In 9 patients with a high serum pre-treatment CA19-9 level, the serum CA19-9 level was useful as a monitoring marker through the treatment or tumor progression. On the other hand, the pre-treatment serum CA19-9 level did not correlate with the clinical stage or prognosis. In conclusion, the phenomenon that the serum levels of CA19-9 increase in testicular germ cell tumor patients is not extremely rare, and in NSGCT, especially in EC or YS, the serum CA19-9 can be a useful tumor marker.

[Clinical evaluation of urinary nuclear matrix protein 22 as a marker for bladder cancer].

The purpose of this study is to evaluate the clinical usefulness of urinary nuclear matrix protein 22 (NMP22) as a marker for bladder cancer. We examined the positive rates of NMP22 test, urinary cytology and bladder tumor antigen (BTA) test, and compared the positive rate of NMP22 test with that in urinary cytology and BTA test. Urine samples were obtained from 50 patients with histologically confirmed bladder cancer before the treatment. The samples were examined by NMP22 test, urinary cytology and BTA test. In 50 patients with bladder cancer, the overall positive rate was 40% for NMP22 test, 40% for urinary cytology, and 16% for BTA test. A combination of NMP22 test and urinary cytology showed a significantly higher positive rate (54%) as compared to NMP22 test or urinary cytology alone. When NMP22 test and urinary cytology were compared for tumor size, number, shape, stage and grade, NMP22 test showed a significant higher positive rate than urinary cytology in grade 1 bladder cancer. In conclusion, although NMP22 test and urinary cytology gave a similar positive rate, a combination of NMP22 test and urinary cytology is more useful than the NMP22 test or urinary cytology alone for monitoring of bladder cancer.

Isolation of an androgen-inducible novel lipocalin gene, Arg1, from androgen-dependent mouse mammary Shionogi carcinoma cells.

Here we report isolation of an androgen-regulated novel gene from an androgen-dependent mouse mammary Shionogi carcinoma SC-3 cell line. Using a polymerase chain reaction-based subtraction method and Northern blotting analysis, we isolated four androgen-inducible genes from SC-3 cells. Nucleotide sequencings identified three of the genes as cyclin D1, beta-catenin, and fatty acid synthase, respectively, but the fourth, a gene tentatively named as Arg1 (androgen-regulated gene 1), remained undefined. The cloned 2.0-kb sized Arg1 cDNA encoded 414 amino acid sequences. The deduced amino acid sequences, sharing about 30% homology with cathepsin family members at a protein level, had relatively conserved residues around the three proteinase active sites reported earlier. In Northern blotting, Arg1 mRNA was found in kidney, heart, lung, and to a lesser degree, in spleen and liver. Its transcripts were also detected in male reproductive organs on RT-PCR. In addition, its expression levels in prostate were markedly reduced after castration. Unexpectedly, Arg1-expressing COS1 cells showed no significant proteinase activity to various synthesized substrates under neutral or acidic conditions in this study. This might have been due to the replacement of the cysteinyl active site for proteinase to serine residue in the Arg1 amino acid sequences. Given that Arg1 also contains a lipocaline signature known as a binding motif for small hydrophobic molecules at the center of its amino acid sequences, Arg1 is a lipocalin family gene regulated by androgens in prostate and Shionogi carcinoma cells.

Lower ureteral replacement using a tubularized gastric segment.

OBJECTIVES: To review our early experience with the use of a gastric segment for lower ureteral replacement in patients with bilateral ureteral stenosis after pelvic radiotherapy. METHODS: Four adult patients (three women and one man) underwent bilateral ureteral substitution using stomach. All patients received whole pelvic irradiation for malignant disease and had undergone bilateral nephrostomy because of severe bilateral ureteral stenosis. The postoperative follow-up period was 11 to 50 months. RESULTS: No major complication was recognized, and the bilateral nephrostomy tubes were removed in all patients. Three female patients could void urethrally without incontinence, and the male patient needed regular self-catheterization. The three women were alive with normal renal function at a follow-up of 11 to 50 months. The man had a vesicorectal fistula 8 months postoperatively, and colostomy was performed. He died of a cause unrelated to the operation 11 months after surgery. CONCLUSIONS: Stomach has not been used commonly for ureteral replacement. In patients with bilateral severe ureteral stenosis after pelvic radiotherapy, ureteral substitution with a gastric segment can be safely performed and will increase the patient's quality of life.

Thymidine phosphorylase/platelet-derived endothelial cell growth factor (PD-ECGF) associated with prognosis in renal cell carcinoma.

We investigated the correlation between thymidine phosphorylase (TP)/platelet-derived endothelial cell growth factor (PD-ECGF) expression, angiogenesis, and prognosis in renal cell carcinoma (RCC) patients. We prepared paraffin block specimens from 56 postradical nephrectomy RCC patients. The preparations were immunohistochemically stained using anti-CD34 antibody and anti-TP antibody. Angiogenic findings were evaluated based on both microvessel density (MVD) and renal arteriography findings as classified by Roosen et al. TP expression showed heterogeneity in 56 patients: 11 (19.6%) were negative, 28 (50.0%) weak, and 17 (30.4%) positive. There was no correlation between TP expression, MVD, and renal arteriography. There was no TP expression in chromophobe types. Univariate analysis showed a significant correlation between survival and TP expression, patient age, tumor infiltration type, pathologic T- and N-stages, venous involvement, distant metastasis, and tumor grade. There was no correlation between survival and MVD or renal arteriography. Multivariate analysis showed a significant correlation between survival and pathologic T-stage, distant metastasis, tumor infiltration type, and TP expression. TP expression in RCC may be an independent prognostic factor rather than just an index for angiogenesis.

Enhancement of sensitivity to capecitabine in human renal carcinoma cells transfected with thymidine phosphorylase cDNA.

The purpose of the present study was to examine directly the role of thymidine phosphorylase (TP) in the sensitivity of renal cell carcinoma (RCC) to a novel fluoropyrimidine carbamate, capecitabine. TP cDNA-transfected RCC are used in these experiments to provide a basis for improved therapeutic benefit in chemoimmunotherapy. Human RCC line KU2 cells were transfected with pcDNA3.1/zeo(+) with or without human TP cDNA by the lipofectin method. We established a clone transfected with pcDNA3.1/zeo(+)/TP (KU2-TP15) and a clone transfected with pcDNA3.1/zeo(+) as a control (KU2-C1). TP expression levels (mean +/- SD) examined by enzyme-linked immunosorbent assay (ELISA) were 1.3 +/- 0.14 U/mg protein in KU2, 1.6 +/- 0.57 U/mg protein in KU2-C1 and 216 +/- 25.6 U/mg protein in KU2-TP15. Immunohistochemical staining of subcutaneous tumors established in Balb/c nu/nu mice showed that KU2-TP15 was strongly positive for TP expression, whereas KU2 and KU2-C1 were negative. Sensitivities in vitro to 5-fluorouracil (5FU), 5'-deoxy-5-fluorouridine (5'DFUR) and capecitabine in KU2-TP15 were significantly enhanced compared with those in KU2 or KU2-C1. A moderate but statistically significant bystander effect was observed in vitro. KU2-TP15 tumors showed significant increase in the in vivo sensitivities to 5'DFUR and capecitabine as compared with the vehicle alone while KU2-C1 tumors did not. The difference in tumor-free rate in mice bearing KU2-TP15 at 2 months after the cessation of treatment was statistically significant between the capecitabine treatment group and the controls, the 5FU treatment group and the 5'DFUR treatment group. The present study clearly provides direct evidence for the role of TP in mediating the sensitivity of RCC to capecitabine.

[A case of giant small cell carcinoma of the prostate].

A 64-year-old man having backbone pain was referred to our institute, and laboratory examinations revealed that he was suffering from severe renal failure. Abdomino-pelvic CT revealed bilateral hydronephrosis, a giant prostate over 500 g in weight, and multiple para-aortic lymph node metastasis. Histological diagnosis of the prostate was small cell neuroendocrine carcinoma. Serum neuron-specific enolase (NSE) level was slightly high reflecting the positive immunohistochemical staining, but serum PSA remained within normal limits. The patient was treated with hormone-chemotherapy after successful treatment of the renal failure, but he died on the 74th hospital day. Small cell carcinoma is known to have a high rate of malignancy and metastasis from an early stage. Several giant prostatic tumors have been reported previously, but this case is considered to be the second gigantic small cell carcinoma in the Japanese literature.

Primary testicular plasmacytoma with hydrocele of the testis.

A case of primary testicular plasmacytoma complicated with hydrocele of the testis is reported. An 86-year-old man presented with hydrocele of the right testis. High inguinal orchiectomy was performed as the preoperative aspiration cytology of the hydrocele fluid showed atypical cells. Immunohistochemical study of the right testis revealed testicular plasmacytoma positive for IgG. He remained well 9 months after the orchiectomy. This is the second reported case where the preoperative diagnosis of testicular plasmacytoma was made based on the hydrocele fluid cytology.

Improvement of ureteroileal anastomosis in orthotopic ileal neobladder with modified le duc procedure: short submucosal tunnel technique.

PURPOSE: A modified Le Duc procedure with a short submucosal tunnel was applied for ureteroileal implantation in ileal orthotopic neobladder and bladder augmentation with the ileum. We assessed the rate of stenosis and ureteral reflux at the ureteroileal anastomosis after this procedure. MATERIALS AND METHODS: Two women and 22 men underwent radical cystectomy and creation of a Hautmann ileal neobladder for invasive bladder cancer. Another woman underwent ileal bladder augmentation with bilateral ureteral reimplantation into the ileal segment. Ureteroileal anastomosis was performed using the modified Le Duc technique in 48 renoureteral units. Followup in all patients included retrograde cystography done before discharge home and excretory urography, renal ultrasonography or abdominal computerized tomography every 4 to 6 months. Followup was 11 to 39 months in 23 of the 25 cases. RESULTS: Retrograde cystography before discharge home revealed no urinary reflux in any reimplanted ureter. There was no ureteral stenosis or reflux in 20 male and 3 female patients (44 renoureteral units) who voided successfully without catheterization. A unilateral ureteral stricture at the ureteroileal anastomotic site in 1 man who voided successfully was treated with endoscopic surgery. Bilateral slight upper urinary tract dilatation caused by ureteral reflux was present in another man who did not void successfully. CONCLUSIONS: The modified Le Duc technique is simple and safe for forming an ureteroileal anastomosis in ileal orthotopic neobladder creation. It appears to have a low ureteral stenosis and reflux complication rate in patients who successfully void postoperatively.

Segmental multicystic dysplastic kidney in an adult woman.

We report a case of unilateral segmental multicystic dysplastic kidney (SMCDK) in an adult woman. A 42-year-old woman presented with abdominal distension and gross hematuria. The preoperative diagnosis was cystic renal cell carcinoma, and a radical nephrectomy was performed. Histopathologically, the resected kidney was SMCDK with severe hydronephrosis.

Post-traumatic high flow priapism: demonstrable findings of penile enhanced computed tomography.

Post-traumatic high flow priapism is a rare disease. A review of English published reports revealed 63 cases. Enhanced computed tomography (CT) of the penis has not previously been used as a diagnostic method for post-traumatic high flow priapism. We present a case of post-traumatic high flow priapism diagnosed with enhanced CT of the penis. Additionally, diagnostic modalities for post-traumatic high flow priapism are discussed with review of published work.

Cisplatin-induced vomiting depends on circadian timing.

We examined whether the clock time of cisplatin plus antiemetic and diuretic administration affects the amount of cisplatin-associated emesis and severity of renal toxicity. We treated 22 patients with urogenital cancer with two courses of chemotherapy containing 70 mg/m2 of cisplatin. Cisplatin together with furosemide was administered in the morning (05:00) or evening (17:00) during two courses 1 month apart in a crossover fashion. Ondansetron was given either before or after cisplatin to control nausea and vomiting. The number of vomiting episodes, serum creatinine, serum urea nitrogen (BUN), creatinine clearance, and urinary beta-N-acetyl glucosamidase (NAG) concentration were evaluated before and after each treatment course. Regardless of the timing of ondansetron, morning compared to evening cisplatin was always associated with greater vomiting in the first treatment course. However, prophylactic administration of ondansetron markedly diminished the impact of the clock time of cisplatin administration. Serum creatinine transiently decreased rather than increased 14 days after cisplatin and furosemide administration, while NAG excretion increased 3 days after cisplatin and furosemide administration. In the first course, serum creatinine levels were similar regardless of the clock time of cisplatin and furosemide administration. However, in the second course, serum creatinine rose in patients given evening cisplatin and furosemide, while it remained unchanged in those given morning cisplatin and furosemide. Moreover, the first course morning cisplatin and furosemide treatment was associated with less change in NAG excretion (less kidney toxicity) than the first course of evening cisplatin and furosemide treatment. The second course evening cisplatin and furosemide treatment was associated with an increase in NAG excretion compared to the first course of treatment, while morning cisplatin and furosemide treatment in the second course showed less change in NAG excretion compared to the first course. The clock time of cisplatin administration had an impact on the frequency of emesis. Prophylactic ondansetron, however, diminished the time-of-day dependency of cisplatin-induced vomiting. Administration of cisplatin and furosemide in the morning rather than evening appears to cause less renal damage, and this damage may be further reduced with aggressive hydration and routine administration of furosemide.

Transitional cell carcinoma in the ileal conduit following radical cystectomy and nephroureterectomy.

We report a case of transitional cell carcinomas (TCCs) at the terminal of ileal conduit and right ureteroileal junction after cystectomy and left nephroureterectomy. When upper urinary tract tumor occurs after cystectomy with ileal conduit, it is necessary to beware of the recurrence of TCC in the ileal conduit.

Predominant expression of fibroblast growth factor (FGF) 8, FGF4, and FGF receptor 1 in nonseminomatous and highly proliferative components of testicular germ cell tumors.

Nonseminomatous components within testicular germ cell tumors affect patient prognosis to varying degrees. These components are well known to mimic early embryonic totipotential tissues. Prompted by the recent observation that fibroblast growth factor (FGF) 8, FGF4, and FGF receptor (FGFR) 1 are required for the growth of early postimplantational embryonic tissues, we investigated the expressions of FGF8, FGF4, and FGFRI in surgically resected specimens of primary testicular germ cell tumors using an immunohistochemical method. All cases of embryonal carcinoma (14 cases), yolk sac tumor (3 cases), and choriocarcinoma (3 cases) showed positive immunostaining for FGF8, FGF4, and FGFR1. In contrast, out of 13 cases of seminoma, immunostaining was negative for FGF8, FGF4, and FGFR1 in 8 cases (61.5%), 6 cases (46.1%), and 7 cases (53.8%), respectively. In 7 cases of mature and immature teratoma, most areas showed negative immunostaining. In addition, the Ki-67 labeling index showed extremely high mitogenic activity in embryonal carcinoma, yolk sac tumor, and choriocarcinoma, which are precisely the carcinomas with the highest expressions of FGF8, FGF4, and FGFR1. It is in keeping with the immunohistochemical result that murine teratocarcinoma P19 cells were shown to express FGF8, FGF4, and FGFRI only under undifferentiated growth conditions. Taken together, these findings confirm the involvement of FGF8, FGF4, and FGFR1 in highly proliferative conditions of nonseminomatous germ cell tumors.