Biomedical subjects
Publications and source records attributed to S Kamidono.
We report a patient with squamous cell carcinoma that developed at the ureteroileal anastomosis and extended into the ileal conduit 11 years after a radical cystectomy for transitional cell carcinoma of the bladder. To our knowledge, this is the first report to document the development of a squamous cell carcinoma in an ileal conduit after a radical procedure for bladder cancer.
BACKGROUND: The presence of proliferating cell nuclear antigen (PCNA) has been suggested as a more important prognostic marker than either grade or mitotic index in the prognosis of patients with renal cell carcinoma. We assessed the immunoreactivity of PCNA in primary lesions and pulmonary metastases from patients with renal cell carcinoma and correlated the results with various histopathologic features and prognostic factors. METHODS: We studied the relationship between PCNA expression and clinical prognostic factors from resected primary lesions and pulmonary metastases from 10 patients and primary lesions from 32 patients with renal cell carcinoma without metastases. The cells were immunohistochemically stained with PCNA monoclonal antibody (PC-10) and 1000 nuclei were counted. The results were expressed as a ratio of stained to total cells (PCNA labeling index, LI %). RESULTS: The PCNA LI of pulmonary metastatic nuclei was significantly higher than the PCNA LI of renal lesions either from patients with (P < 0.05) or without (P < 0.01) metastases. Also, the mean PCNA LI of the pulmonary lesions in patients dying within 3 years of diagnosis was higher than the mean PCNA LI of patients surviving greater than 3 years. CONCLUSION: Our findings suggest that the PCNA LI, which was determined by immunohistochemical analysis, is an important marker reflecting the biologic behavior of renal cell carcinomas. The degree of PCNA expression in this study was of prognostic significance.
BACKGROUND: We reviewed the outcomes for patients with penile cancer to determine factors predictive of their survival. METHODS: Between 1966 and 1996, 59 patients with penile cancer were treated at Kobe University Hospital. The median follow-up period was 109 months (range, 4 to 240 months). The prognostic factors were determined by multivariate analysis. Disease progression rates, according to stage and the type of surgery, were studied. RESULTS: The 5- and 10-year, cause-specific survival rates were 75.9% and 73.8%, respectively. Lymph node involvement, tumor stage, and tumor differentiation were the independent risk factors identified by multivariate analysis. Among the patients at stage 1 and 2, none of the 29 patients treated with early lymphadenectomy showed recurrence in the inguinal region, while 4 (27%) of 15 patients without lymphadenectomy showed such recurrence. CONCLUSION: Our results suggest that tumor stage, lymph node involvement, and tumor differentiation are significant prognostic factors for survival, and that early inguinal lymphadenectomy would improve the prognosis of patients with stage 1 or 2 penile cancer.
We investigated the expression of MAGE genes in 10 renal cell carcinoma (RCC) cell lines, 50 RCC tumor samples and 5 normal kidney samples using reverse transcription-polymerase chain reaction (RT-PCR). MAGE-1, -2, -3 and -4 genes were expressed in 4, 1, 10 and 3 of 10 RCC cell lines, respectively, and 11, 8, 38 and 15 of 50 RCC samples. In contrast, there was no expression of MAGE genes detected in any of the normal kidneys. The incidence of the expression of plural MAGE genes in high stage RCC was significantly higher than that in low stage RCC. An analysis based on clinicopathological factors revealed that MAGE-4 gene was more frequently expressed in clear cell subtype than in granular cell subtype RCCs. Our results suggest that owing to the high incidence of MAGE gene expression in RCC, a large proportion of patients could be suitable candidates for novel immune therapies involving tumor-specific antigens encoded by MAGE genes.
The mutant p53 gene was transfected into ACHN, a wild-type p53-containing human renal cell carcinoma (RCC) cell line. The colony forming efficiency in soft agar in the mutant-type p53-transfected cell line (ACHN/MP) was significantly higher than that in the vector-only transfected control cell line (ACHN/C). The anti-Fas monoclonal antibody (CH11) induced apoptosis in the ACHN/C cells in a dose-dependent manner, whereas the effect of CH11 on the ACHN/ MP cells was markedly suppressed. In addition, the cytotoxic effect of CH11 on the ACHN/MP cells was augmented by the pretreatment with interferon- , but the corresponding effect on ACHN/C cells was not. These findings suggest that Fas-mediated therapy could be a novel approach to RCC, if interferon- treatment is added according to the p53 gene status.
The synergistic anti-tumor effect of 13-cis retinoic acid (13-cRA) and interferon-alpha/beta (IFN-alpha/beta) was investigated using a highly metastatic mouse renal cell carcinoma cell subline (RenCa/F). Although 13-cRA inhibited tumor growth in vivo as well as in vitro, IFN-alpha/beta did not. Combined administration of 13-cRA and IFN-alpha/beta significantly enhanced the anti-tumor effect of 13-cRA. The retinoic acid receptor (RAR)-alpha and RAR-gamma were expressed in RenCa/F cells. Treatment with IFN-alpha/beta did not influence the expression level of these receptors at the mRNA level, which suggests that the synergism of 13-cRA and IFN-alpha/beta is not mediated through the RAR.
OBJECTIVE: To analyze the urodynamic characteristics of neobladders, we conducted a pressure-flow study in patients with orthotopic urinary reservoirs. PATIENTS AND METHODS: From 1986 to 1996, 90 patients underwent bladder replacement following cystectomy, using a right colonic, ileocolic, ileal, or sigmoid colonic segment. The subjects were 38 patients (31 men and 7 women) with stable urination and no evidence of cancer recurrence, urethral stricture, urinary tract infection or vesicoureteral reflux. Their mean age was 60.5 years, with a range of 38 to 77 years. Information on neobladder function, such as desire to void, force of micturition, urinary incontinence and other complaints, was obtained by questionnaire. A pressure-flow study was performed in all patients 3 months to 103 months postoperatively to evaluate total reservoir pressure, abdominal pressure and subtracted reservoir pressure during filling and voiding phases. RESULTS: Ten of 38 patients (26.3%) were dissatisfied with their neobladder function, due to weakness of urinary sensation, loss of urinary force and enuresis. In 6 of the 7 patients with enuresis, the urinary reservoir had been created by Heineke-Mikulicz's procedure of detubularization; 4 of these patients had a high degree (over 40 cmH2O) of phasic contraction during the filling phase. In only 2 of the 38 patients, a pressure-flow study showed an almost same pattern as that obtained with a normal urinary bladder. Twelve patients had increased electromyogram of the external urethral sphincter during the voiding phase, while half of the 38 patients showed a flat electromyogram during both the filling and voiding phases. Thus, 31 of 38 patients revealed a sphincter dyssynergia pattern. Mean total reservoir pressure at maximum cystometric capacity was 65.5 +/- 42.1, 48.4 +/- 19.0, 66.0 +/- 61.0 and 107.0 +/- 43.3 cmH2O in ileal, ileocecal, right colonic and sigmoid neobladders, respectively. The value for sigmoid neobladder was statistically different from that for ileocecal neobladder (p < 0.05). Mean total reservoir pressure at maximal flow was 73.1 +/- 42.4, 56.4 +/- 22.6, 88.9 +/- 69.4 and 94.0 +/- 31.8 cmH2O in ileal, ileocecal, right colonic and sigmoid neobladders, respectively. There were no statistically significant differences among these values. The ratio of subtracted reservoir pressure to total reservoir pressure was lower at maximal flow than at onset. Subtracted reservoir pressure may contribute to total reservoir pressure to a greater extent in sigmoid neobladders than in other types of neobladder. CONCLUSIONS: 1. Enuresis may have various causes such as external sphincter dysfunction and involuntary contraction of the reservoir. 2. Urine is evacuated not only by abdominal pressure but also by subtracted reservoir pressure in neobladders. 3. Sphincter dyssynergia due to absence of the detrusor muscle may be one cause of dysuria.
PURPOSE: We determined a rational strategy for treatment of patients with retrograde ejaculation in the era of modern assisted reproduction technology. MATERIALS AND METHODS: In 7 consecutive patients medical treatment or retrieval of spermatozoa from the bladder was performed at a male infertility clinic. RESULTS: Antegrade ejaculation was restored in 3 patients, and spermatozoa were retrieved from the bladder and used for assisted reproduction in 3. Spermatozoa with good oolemma penetrating ability were collected by seminal vesicle massage. CONCLUSIONS: Modern assisted reproduction technology is a powerful treatment option for retrograde ejaculation when combined with a technique to retrieve spermatozoa of good quality from the bladder.
The efficacy and tolerability of propiverine hydrochloride (20 mg/day) were evaluated in the treatment of a total of 49 Japanese patients (35 with urge incontinence and 14 with stress incontinence) in an open multicenter trial lasting 28 days. The effects on the frequency of urination, urinary incontinence, urinary urgency, and daily living activities were evaluated through the voiding diaries filled out by the patients. Moderate or greater degree of improvement was attained in micturition frequency by 52 and 54% of the patients with urge incontinence and with stress incontinence, respectively, in urinary urgency by 91 and 58%, in urinary incontinence by 97 and 71%, and in daily living activities by 94 and 64%. Although minor adverse reactions (5 patients) and abnormal values in blood chemistry (2 patients) were recorded in 7 patients, all of these patients completed the trial. These results suggest that propiverine hydrochloride is a safe and effective drug of choice for the treatment of not only urge incontinence but also stress incontinence in patients diagnosed in a clinical setting.
PURPOSE: We determined the risk of local recurrence in 64 Japanese patients a median of 69 years old with renal cell carcinoma who were possible candidates for nephron sparing surgery and who underwent radical nephrectomy. MATERIALS AND METHODS: A total of 64 kidneys in which tumors 50 mm. or less were resected were prospectively examined pathologically in 3 mm. sections. The incidence of satellite tumors and the relationship between the pathological findings of the primary and satellite tumors were evaluated. RESULTS: Satellite tumors were identified in 10 of the 64 kidneys (15.6%), a rate similar to that reported in the United States. The correlation of histological findings between primary and satellite tumors was 70% for tumor grade. Satellite tumor grade was less than that of the primary lesion in 3 cases. In 60% of the specimens with multifocal renal cancer satellite tumors were within 10 mm. of the margin of the primary tumor. At this distance, if partial nephrectomy had been performed, the satellite lesions would have been missed in 4 of these 10 patients (40%). Of the 10 kidneys with satellite renal tumors 8 (80%) had vascular invasion of the primary tumor. Multiple logistic regression analysis demonstrated that vascular invasion was a significant predictor of multifocality of renal cell carcinoma. CONCLUSIONS: Our results suggest that vascular invasion is a risk factor for multifocality in Japanese patients with renal cell carcinoma. Therefore, careful and long-term followup is necessary in patients with renal cell carcinoma who have undergone nephron sparing surgery, especially those with vascular invasion of the primary tumor.
Despite recent extensive immunohistochemical studies, the expression patterns of CD44 in testicular germ cell tumors are still controversial. In the present study, we investigated the CD44 gene expression in 40 specimens including 18 seminomas, 16 nonseminomatous germ cell tumors (NSGCT), and 6 normal testes by reverse transcriptase-polymerase chain reaction and Western blotting. Reverse transcriptase-polymerase chain reaction analysis revealed that the standard CD44 isoform (CD44s) was expressed in all of the specimens, whereas the variant CD44 isoforms were highly expressed in NSGCTs but barely detectable in seminomas and normal testes. In addition, we confirmed by direct DNA sequence analysis that the predominantly expressed variant isoform in NSGCTs was CD44v8-10. In germ cell tumors, these results were paralleled in Western blot analysis; that is, CD44s protein was expressed in all of the tumor specimens, whereas high molecular weight variant isoforms were expressed only in NSGCTs. However, at the protein level, no detectable CD44 was expressed in normal testes. These findings show that the combined assessment of CD44 expression patterns at both the RNA and protein levels enables us to distinguish among seminoma, NSGCT, and normal testis specimens; hence, it could serve as a useful practical adjunct to conventional diagnostic methods for testicular germ cell tumors.
PURPOSE: It has been suggested that prepubertal obstruction of the seminal tract may result in irreversible damage to spermatogenesis. We examined whether accelerated apoptosis in prepubertal obstruction has a deleterious effect on spermatogenesis in adulthood. MATERIALS AND METHODS: We studied apoptotic changes of both prepubertal and adult obstructive azoospermia rat models by means of an in situ end-labeling technique and electron microscopy, and by examination of the pathological changes. Four groups were designed as follows. Group 1: bilateral vasectomies performed at ten days of age (prepubertal vasectomy model); Group 2: sham operation performed at ten days of age; Group 3: bilateral vasectomies performed at eight weeks of age (adult vasectomy model); Group 4: sham operation performed at eight weeks of age. Three rats in each group were killed weekly, and the testes and epididymides removed and weighed. Germ cell apoptosis was detected by in situ end-labeling, and the apoptotic index (AI) was calculated by dividing the number of in situ labeled cells by the total number of seminiferous tubules. The developmental change of testis and epididymis, the diameter of seminiferous tubules, and the number of spermatogonia were also examined. Histopathological examination of tubular diameter and the number of spermatogonia and Sertoli cells was done by PAS staining. The number of spermatogonia divided by the number of Sertoli cells per tubular cross section was expressed as spermatogonia-Sertoli cell ratio (S-S ratio). RESULTS: At 3 and 4 weeks of age, rats of group 1 demonstrated a significantly higher apoptotic index of germ cells than did the sham-operated rats of group 2 (p <0.05). No significant differences were seen between groups 3 and 4. The increased apoptosis in group 1 seemed to be reduced by the formation of epididymal granulomas. The tubular diameter of group 1 at 16 weeks of age was significantly smaller than that of groups 2, 3, or 4. The S-S ratios were lower at stages IV, V and VI in group 1 at 16 weeks-of-age following vasectomy at 10 days of age compared with that in group 2. CONCLUSIONS: We conclude that an increase of apoptotic degeneration of germ cells in the prepubertal period may cause irreversible changes in germinal stem cells, resulting in hypospermatogenesis in adulthood.
PURPOSE: This study was designed to investigate the significance of the interaction between CD44 and hyaluronic acid in the development of human prostate cancer. MATERIALS AND METHODS: We transfected the standard CD44 isoform (CD44s) cDNA into PC3, a human prostate cancer cell line that barely expresses CD44s protein. The effects of the reintroduction of CD44s into PC3 cells on the ability to bind hyaluronic acid (HA) were analyzed by the cell adhesion assay and by the cell migration assay. The in vitro growth rate of CD44s transfected PC3 was measured by using the MTT assay. We then evaluated the in vivo tumor development of CD44s transfected PC3 cells by subcutaneous, intravenous, and intraperitoneal injection models in athymic nude mice. RESULTS: The introduction of CD44s in PC3 cells markedly enhanced the binding and migration of these cells to HA, but not to other extracellular matrix molecules. In vitro growth of CD44s-transfected PC3 was found to be significantly decreased. In addition, the CD44s-transfected PC3 cells also demonstrated reduced tumorigenicity and metastatic potential in in vivo experimental models. CONCLUSIONS: These findings suggest that the CD44s downregulation plays an important role in the development of human prostate cancer, in part through reduction of the ability to bind HA.
The reported incidence of satellite tumor lesions in kidneys resected by radical nephrectomy for renal cell carcinoma (RCC) is 7-25%; however, genetic analyses of satellite tumors in comparison with those of main tumor lesions have not been performed well. In the present study, we investigated the incidence of loss of heterozygosity (LOH) at chromosome arms 3p, 6q, 8p, 9p, 9q, and 14q using 18 microsatellite markers in 10 nonpapillary RCCs of 50 mm or less in diameter and the accompanying satellite tumor lesions to evaluate the genetic alterations in main and satellite tumors. LOH was detected in 10, 3, 5, 3, 2, and 3 cases at chromosome arms 3p, 6q, 8p, 9p, 9q, and 14q, respectively. In addition, primary and satellite tumor lesions in 8 of 10 cases exhibited identical patterns of LOH on the 18 loci examined. In the remaining two cases, both main and satellite tumors demonstrated LOH on the common seven and three loci, respectively, whereas for another locus, LOH was observed only in the satellite tumor lesions. The similarity of LOH patterns detected in main and satellite tumor lesions indicates that the presence of satellite tumors might be the result of intrarenal metastasis from the main tumor lesion. These findings strongly suggest that even in case of small nonpapillary RCC, nephron-sparing surgery might carry the risk of failing to prevent postoperative local recurrence due to the incomplete resection of unrecognized satellite tumors with genetic alterations similar to those of the main tumor.
Leukocyte functions (superoxide production and phagocytosis) were evaluated in patients with testicular cancer who had undergone super-high-dose chemotherapy (SHDT) with peripheral blood stem cell transplantation (PBSCT). In 5 patients with advanced or relapsed testicular cancer who received 8 cycles of SHDT with PBSCT, we measured superoxide production activity by phorbol myristate acetate (PMA) stimulation, as well as phagocytic activity using latex particles before and after PBSCT. The median time to reach a leukocyte count of > or = 1,000/microl was 9 days after PBSCT. Superoxide production activity was significantly decreased on day 7 compared with the pre-chemotherapy level. However, it recovered by day 12 and sustained such a level thereafter. Phagocytic activity was within the normal range on day 7 but declined slightly on days 12 and 21 compared with the pre-chemotherapy level. Our results indicate that leukocyte function and leukocyte count recover promptly following PBSCT and that PBSCT is a safe and convenient adjunctive therapy after SHDT for patients with advanced testicular cancer.
The aetiology of ACTH-independent macronodular adrenal hyperplasia (AIMAH) is uncertain. We examined a 55 year old man with Cushing's syndrome due to AIMAH, whose cortisol levels increased after stimulation with lysine-8-vasopressin (LVP) in vitro as well as in vivo. Abdominal MRI revealed nodular enlargement of both adrenal glands. No adenoma was evident on pituitary MRI. 131I-adosterol scintigraphy exhibited marked uptake into both adrenal glands. Although baseline plasma cortisol levels were within normal limits, urinary free cortisol excretion was 3-fold higher than the upper limit of the normal range. Plasma ACTH levels were undetectable. Oral dexamethasone failed to suppress plasma cortisol levels irrespective of dose, and administration of corticotrophin releasing hormone failed to increase plasma ACTH and cortisol levels. LVP injection failed to increase plasma ACTH levels, but elicited an increase in plasma cortisol levels. The direct stimulatory effect of LVP on cortisol secretion was confirmed in vitro in cultured adrenocortical cells from macronodules obtained at surgery. Food intake, gastric inhibitory polypeptide (GIP), or octreotide administration, which were reported to regulate cortisol release in patients with AIMAH, failed to affect plasma cortisol levels. In conclusion, plasma cortisol responsiveness to LVP, GIP, and octreotide is heterogeneous in patients with AIMAH.
OBJECTIVE: To investigate the pitfalls of measuring postvoid residual urine volume (PVR) in patients with orthotopic neobladders, in an out-patient clinic. PATIENTS AND METHODS: Fifteen patients with orthotopic neobladders were enrolled in the study; five patients had a colonic neobladder, five an ileocolic neobladder and five a sigmoid neobladder. The PVR was compared after measuring by catheterization under fluoroscopic monitoring after normal or forced voiding. RESULTS: The PVR after forced voiding was always less than that after natural voiding, regardless of the type of neobladder. CONCLUSIONS: Patients with orthotopic neobladders may have a higher PVR after voiding naturally at home than when the PVR measured in hospital.
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