Usefulness of diffusion-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging in the diagnosis of prostate transition-zone cancer.

BACKGROUND: Conventional T2-weighted (T2-WI) magnetic resonance imaging (MRI) has poor sensitivity for prostate transition-zone (TZ) cancer detection. PURPOSE: To retrospectively evaluate the clinical value of diffusion-weighted MRI (DW-MRI) and dynamic contrast-enhanced MRI (DCE-MRI) in combination with T2-WI for the diagnosis of TZ cancer. MATERIAL AND METHODS: Twenty-six TZ cancers in 23 patients with at least one tumor (tumor size >10 mm) located predominantly in the TZ were included in the study. Sixteen peripheral-zone (PZ) cancers in 12 patients with PZ cancer but without TZ cancer (control group) were selected by step-section pathologic maps. All patients underwent MRI and radical prostatectomy. MRI was obtained by a 1.5T superconducting system with a phased-array coil. Imaging sequences were T2-WI with fat saturation (FST2-WI), DW-MRI (single-shot echoplanar image, b=0 and 1000 s/mm(2), apparent diffusion coefficient [ADC] map findings), and DCE-MRI (3D fast spoiled gradient recalled [SPGR], contrast medium [0.2 mmol/kg], total injection time 5 s, image acquisition 30, 60, and 90 s). Sensitivity, specificity, accuracy, and positive predictive value (PPV) for the diagnosis of TZ cancer were evaluated in four protocols: A) FST2-WI alone, B) FST2-WI plus DW-MRI, C) FST2-WI plus DCE-MRI, D) FST2-WI plus DW-MRI plus DCE-MRI. RESULTS: Sensitivity, specificity, accuracy, and PPV in protocol A (FST2-WI alone) were 61.5%, 68.8%, 64.3%, and 76.2%, respectively. FST2-WI plus DW-MRI (protocol B) improved the sensitivity, specificity, accuracy, and PPV. In FST2-WI plus DW-MRI plus DCE-MRI (protocol D), the number of true-negative lesions increased and false-positive lesions decreased, and the sensitivity, specificity, accuracy, and PPV were 69.2%, 93.8%, 78.6%, and 94.7%, respectively. There was a significant difference between protocols A and D (P<0.05). CONCLUSION: Adding DW-MRI to FST2-WI in the diagnosis of prostate TZ cancer increased the diagnostic accuracy. The addition of DCE-MRI may be an option to improve the specificity and PPV of diagnosing TZ cancer with FST2-WI and DW-MRI.

High levels of nm23 expression are related to cell proliferation in human prostate cancer.

Reduced expression of the nm23 gene has been correlated with high metastatic potential in rodent mammary tumors and human breast cancer. The expression of this gene was studied in human prostate cancer tissue from 43 patients by immunohistochemistry using anti-nm23-H1 antibodies. Intense immunostaining was observed in 71.4% of the patients with clinical stage D disease as compared to 23.1% in clinical stage B and 18.7% in stage C disease (P < 0.05). Similarly intense immunostaining was present in 75% of poorly differentiated cancers versus only 28.6% in men with moderately differentiated cancer. nm23-H1 mRNA expression was measured by Northern blot analysis during phases of the cell cycle in DU 145, PC-3, LNCaP, and TSU-Prl human prostate cancer cell lines. Cells were synchronized in G0-G1 phases by serum deprivation and at the G1-S boundary by aphidicolin. nm23-H1 mRNA levels declined during serum deprivation and increased rapidly following serum addition. Although nm23-H1 was expressed continuously throughout the cell cycle, higher expression was observed in late G1, early S, and G2-M phases. These results indicate that nm23-H1 gene expression is related to the proliferative phase of cell growth.

Alterations of beta- and gamma-catenin in N-butyl-N-(-4-hydroxybutyl)nitrosamine-induced murine bladder cancer.

Abnormal degradation of beta-catenin caused by alteration of the glycogen synthase kinase-3beta (GSK-3beta) consensus motif is an important step for carcinogenesis. We hypothesize that beta- and gamma-catenin may play an important role in the pathogenesis of bladder cancer. We tested this hypothesis through analysis of beta- and gamma-catenin in both murine and human bladder cancers. A murine bladder cancer model was prepared by use of N-butyl-N-(-4-hydroxybutyl)nitrosamine (BBN) in 6-week-old male B6D2F1 mice. After 4, 8, 12, 16, 20, 24, and 28 weeks of BBN treatment, bladder specimens were harvested and analyzed for both protein and gene expression for beta- and gamma-catenin. Mutational analysis of the NH(2)-terminal regulatory domains of beta- and gamma-catenin was performed in each specimen by PCR-single-strand conformational polymorphism (SSCP) analysis. Mutations were further confirmed by direct DNA sequencing with a dye terminator method. Human bladder cancer specimens with normal tissues, dysplasia, carcinoma in situ, and carcinoma of grades, 1, 2, and 3 were also analyzed for beta- and gamma-catenin expression. beta- and gamma-catenin were analyzed for mutations by SSCP and direct DNA sequencing. Intracellular accumulation of beta- and gamma-catenin was observed in 6 of 20 invasive carcinoma specimens. There was no intracellular accumulation of beta- and gamma-catenin in mucosal dysplasia, papillary or nodular dysplasia, and carcinoma in situ specimens. On an SSCP analysis for beta-catenin, abnormal bandshifts were detected in two invasive carcinomas with intracellular beta-catenin accumulation. Further sequencing revealed two mutations [AGT(S) to ATT(I) and TCT(S) to CCT(P)] within the consensus motif for GSK-3beta phosphorylation. On the other hand, SSCP analysis for gamma-catenin followed by sequencing revealed three mutations in two invasive carcinomas with intracellular accumulation of gamma-catenin. These three alterations affected the 3' downstream region outside the GSK-3beta phosphorylation site [ACC(T) to GCC(A), CTC(L) to ATC(I), and CTC(L) to ATG(M)]. In human bladder cancer, beta- and gamma-catenin expression was significantly weaker than in normal bladder. On SSCP analysis one abnormal bandshift was observed in high-grade human bladder cancer with intracellular beta-catenin accumulation. DNA sequencing revealed mutation TCT(S) to TGT(C). In summary, alterations in beta- and gamma-catenin are late events favoring tumor progression in mouse BBN-induced bladder cancer. Changes affecting the GSK-3beta phosphorylation site appear to be associated with activation of beta-catenin, but not with activation of gamma-catenin. In human blabber cancer, beta- and gamma-catenin expression is similar to the expression in the mouse model. The present study demonstrates that beta- and gamma-catenin may play an important role in bladder cancer progression.

Immunohistochemical analysis of bcl-2 expression in transitional cell carcinoma of the bladder.

AIMS: To evaluate the expression of bcl-2 in transitional cell carcinoma (TCC) of the bladder; to compare bcl-2 expression with clinicopathological findings, p53 immunoreactivity, proliferating cell nuclear antigen (PCNA) expression, 2c deviation index (2cDI), 5c exceeding rate (5cER), and the mean nuclear area (MNA). METHODS: Cystectomy specimens from 77 patients with untreated, non-metastatic TCC of the bladder were studied. Expression of bcl-2, p53 and PCNA was detected immunohistochemically using the following monoclonal antibodies: bcl-2/124, DO-7 and PC10, respectively. Nuclear DNA content was analysed using static cytometry. RESULTS: Bcl-2 was expressed in 19 (24.7%) of 77 TCCs and in 74 (96.1%) of 77 normal samples of transitional epithelium (taken from normal tissue adjacent to the tumour in each case). In all cases, bcl-2 immunoreactivity was more intense in normal transitional epithelium than in TCC. In normal transitional epitehlium and superficial TCC bcl-2 immunoreactivity was observed at the basal layer, and not at the invasive front. Bcl-2 immunoreactivity was invesely correlated with histological grade and p53 immunoreactivity, and was not correlated with the pT category, disease progression, PCNA expression, 2cDI, 5cER, and the MNA. No significant correlation was found between bcl-2 expression and overall survival. CONCLUSIONS: Bcl-2 expression in TCC of the bladder seems to be associated with a less aggressive phenotype and does not play an important role in tumour progression.

Chromosome aberrations in renal tumors detected by fluorescence in situ hybridization.

The aim of this study was to investigate the relationship between chromosome aberrations detected by fluorescence in situ hybridization (FISH) and tumor grade, stage, venous involvement, and DNA ploidy status in 18 renal tumors. Using FISH with chromosome-specific DNA probes, the copy number of pericentromeric sequences on chromosomes 3, 7, 9, and 17 was detected within interphase nuclei in touch preparations from tumor specimens. Monosomy for chromosome 3 was detected in seven of 9 DNA diploid tumors, whereas all DNA aneuploid tumors demonstrated trisomy or tetrasomy for chromosome 7. Moreover, monosomy for chromosome 3 was more frequently shown in the diploid and low-stage tumors than in the aneuploid and high-stage tumors. The percentage of hyperdiploid cells significantly correlated with DNA ploidy status in the case of chromosomes 3 and 7 (p = 0.030, p = 0.007, respectively). The percentage of hyperdiploid cells for chromosome 3 had borderline significance with tumor stage. On the other hand, the percentage of diploid cells for chromosome 17 was significantly correlated with DNA ploidy status and tumor stage (p = 0.030, p = 0.027, respectively). Moreover, the percentage of diploid cells for chromosome 7 in renal cell carcinoma (RCC) with venous involvement was significantly lower than those without venous involvement (p = 0.023). These results suggest that the incidence of chromosomal aberrations detected by FISH is more frequent than the chromosomal aneuploidy reported previously by conventional cytogenetics. Therefore, loss of chromosome 3 may be associated with an early event in RCC carcinogenesis. Gain of chromosomes 3 and 7 is correlated with tumor progression as well as gain and loss of chromosome 17. Study of the chromosomal aberrations may provide a greater understanding of tumor carcinogenesis and progression in RCC.

Condyloma acuminatum in three-year-old girl.

Condyloma acuminatum has been thought to be rare in the pediatric age group because the mode of transmission is venereal. We report a case of a three-year-old girl with condyloma acuminatum. Mode of transmission of a viral agent and factors predisposing to infection are presented.

M-VEC (methotrexate, vinblastine, epirubicin, and cisplatin) with granulocyte colony-stimulating factor for the treatment of urothelial cancer: an effective and safe chemotherapy regimen.

The toxicity of combination chemotherapy is significant, with the most prominent side effect being myelosuppression. To reduce the toxicity, we used a recombinant human granulocyte colony-stimulating factor (rhG-CSF). A total of 52 patients were enrolled in this study. The sites of tumor involvement included the urinary bladder in 24 patients, the renal pelvis in 5, the ureter in 4, lymph nodes in 11, bone in 4, the lung in 1, and miscellaneous sites in 4 patients. The chemotherapy was given in 21-day cycles as follows: 30 mg/m2 methotrexate was given intravenously on day 1, and approximately 24 h later, 3 mg/m2 vinblastine, 30 mg/m2 epirubicin, and 70 mg/m2 cisplatin were given intravenously. The rhG-CSF (2 micrograms/kg per day) was injected subcutaneously on days 3-16 of each cycle. All patients received full doses of the antineoplastic agents on time according to the protocol design. The response rates were 61% for primary sites, 55% for lymph nodes, 0 for bone, and 67% for miscellaneous sites. Of 42 patients evaluated, 5 (12%) achieved a complete response and 20 (48%) achieved a partial response, for an overall response rate of 60%. Of the 42 patients, 27 (64%) are alive, and the median duration of survival is 14 months. The mean nadir white blood count was more than 5,600 cells/mm3. The incidence of mucositis in the total toxic symptoms was low. There was no cardiac toxicity or drug-related death. These results indicate that the present combination chemotherapy with coadministration of rhG-CSF is an effective and safe regimen for the treatment of urothelial cancer.

Factors affecting the outcome of patients with advanced urothelial cancer following chemotherapy with methotrexate, vinblastine, adriamycin, and cisplatin.

Attempts were made to identify factors related to the response of patients treated with intravenous methotrexate, vinblastine, Adriamycin, and cisplatin (M-VAC). The subjects consisted of 54 patients with advanced urothelial cancer whose histological type was transitional-cell carcinoma. The effects of various factors on the response were studied using univariate analysis and a multiple logistic regression model. The following factors were included in the analyses: (1) age, (2) sex, (3) performance status (PS), (4) primary site, (5) histological grade, (6) T category, (7) N category, (8) M category, (9) tumor status, and (10) dose of drugs. In all, 9 patients achieved a complete response and 23 showed a partial response, for an overall response rate of 59% (95% confidence limits, 46%-72%). Univariate analysis revealed that the PS, M category, and dose of drugs were related to the response, and there was a significant correlation among these three factors. In the multiple logistic regression model, the absolute value of t was high for the M category. The presence of distant metastases is an important factor in predicting poor efficacy for the present regimen. The management of metastatic disease will be the subject of further study in the treatment of advanced urothelial cancer.

Downregulation of androgen, estrogen and progesterone receptor genes and protein is involved in aging-related erectile dysfunction.

We hypothesize that downregulation of sex hormone receptors (androgen, estrogen and progesterone receptors) is involved in aging-related erectile dysfunction. To test this hypothesis, we investigated the expression of sex hormone receptors in penile crura of aging rats. A total of 40 rats were divided into four groups based on age (6, 12, 18 and 24 months), and the erectile function was analyzed by the measurement of intracavernous pressure. Gene and protein expressions of sex hormone receptors were analyzed by RT-PCR and immunostaining, respectively. The mean intracavernous pressures of 6-, 12-, 18- and 24-month-old rats were 110.1, 89.6, 73.5 and 42.7 cm H(2)O, respectively. Gene and protein expressions for androgen receptor, estrogen receptor-beta and progesterone receptor were present in similar levels in 6-, 12- and 18-month-old rat crura, but significantly lower or absent in 24-month-old crura. This is the first study to demonstrate that downregulation of sex hormone receptors in aging rat crura is associated with erectile dysfunction.

Activation of the visual cortex imaged by 24-channel near-infrared spectroscopy.

Near-infrared spectroscopy (NIRS) is a noninvasive technique for continuous monitoring of the amounts of total hemoglobin (total-Hb), oxygenated hemoglobin, (oxy-Hb) and deoxygenated hemoglobin (deoxy-Hb). The purpose of the present study was to demonstrate the utility of NIRS in functional imaging of the human visual cortex. A new NIRS imaging system enabled measurements from 24 scalp locations covering a 9 cm sq area. Topographic images were obtained from interpolations of the concentration changes between measurement points. Five healthy subjects between 25 and 49 years of age were investigated. After a resting baseline period of 50 s, the subjects were exposed to a visual stimulus for 20 s, followed by a 50 s resting period in a dimly lit, sound attenuating room. The visual stimulus was a circular, black and white, alternating checkerboard. In four of five subjects the visual cortex was the most activated area during visual stimulation. This is the first reported use of a NIRS-imaging system for assessing hemodynamic changes in the human visual cortex. The typical hemodynamic changes expected were observed; the total-Hb and oxy-Hb increased just after the start of stimulation and plateaued after 10 s of the stimulation period.

Long-term results of endourologic treatment of urinary calculi: investigation of risk factors for recurrence or regrowth.

To evaluate the risk factors related to the long-term outcome of endourologic treatment of urinary calculi, we examined rates of recurrence and regrowth in 167 renal units. The following risk factors were examined: age; previous stone; location, number, size, and composition of stone; and procedures. In our study sample, the overall recurrence and regrowth rates were 17% and 10%, respectively. The earliest recurrence and regrowth appeared at 3 months after treatment, and 71% occurred within 2 years. In 22% of renal units that were estimated to be stone-free, stones appeared later, and 45% of inadequately fragmented stones enlarged. Stones located in a renal calix and pelvis, multiple stones, large stones (more than 20 mm), stones composed of calcium oxalate or calcium phosphate or both, and struvite stones were likely to be risk factors, but there were no significant differences statistically. Although the possibility of several risk factors was suggested in our study, thorough fragmentation of stones and complete removal of fragments, combined with extracorporeal shock wave lithotripsy or chemolysis if needed, is ultimately responsible for successful treatment of urinary calculi.

Comparison of MR imaging and urodynamic findings in benign prostatic hyperplasia.

OBJECTIVE: In benign prostatic hyperplasia (BPH), it is uncertain whether the size of the prostate is related to the degree of urodynamically demonstrated bladder outlet obstruction. We compared MR imaging findings and urodynamic data in patients with surgically confirmed BPH. MATERIALS AND METHODS: We prospectively studied 43 benign prostatic hyperplasia (BPH) patients in whom transurethral resection of the prostate (TURP) was planned. We obtained T1- and T2-weighted images in the transverse and sagittal planes with a 1.5 Tesla superconducting unit. The predicted volume of the inner gland and the peripheral zone were obtained on T2-weighted transverse images. Prostatic protrusion into the urinary bladder (IB protrusion) and the inner gland ratio (IG ratio: inner gland volume/total prostatic volume) were determined. RESULTS: IB protrusion and inner IG ratio were significantly greater in patients with severe stenosis than in those without. A surgical capsule (SC) was seen in 20 of 25 patients (80%) with severe stenosis and 8 of 18 (44%) of those without it. The accuracy of IB protrusion + IG ratio, IB protrusion + surgical capsule, and IB protrusion + IG ratio + surgical capsule was 89%, and that of IG ratio + surgical capsule was 86%. CONCLUSION: The inner gland ratio, protrusion into the bladder, and presence of surgical capsule were the most important factors in bladder outlet obstruction. The probability of outlet stenosis increases in patients with more than two of these criteria.

Urethral caruncle with coexistence of intestinal heterotopia. A case report.

Urethral caruncle is one of the benign disorders which occurs frequently after the menopause. We describe a case of urethral caruncle with intestinal heterotopia, in which infiltration by lymphocytes, invagination of the urethral transitional epithelium causing nest formation, lumen formation, hypervascularity as well as teleangiectasia were observed, suggesting the occurrence of metaplasia in the transitional epithelium preceding the intestinal heterotopia. The aetiology and clinical significance of urethral caruncle exhibiting intestinal heterotopia are discussed.

Concomitant presence of bladder cancer and neurogenic bladder in a patient with HTLV-1 carrier: a case report.

We describe a case of an HTLV-1 carrier who developed bladder cancer and neurogenic bladder. HTLV-1 is thought to alter host immune function and to contribute to the development of other malignancies. It is also sometimes reported that urinary symptoms precede pyramidal symptoms in patients with HAM. To our knowledge, concomitant presence of bladder cancer and neurogenic bladder in an HTLV-1 carrier has not been previously reported.

Secondary plasmacytoma of the testis: report of a case.

We report a case of secondary plasmacytoma of the testis. The patient previously had had plasmacytoma of the nasal cavity, and then recurrences occurred in the right ethmoid sinus, sphenoid sinus, nasopharynx and clavicle before testicular plasmacytoma has developed. This is the 49th case of testicular plasmacytoma reported in the world literature.

Inverted papilloma of the urinary bladder: a case evaluated for malignant potential.

We report a case of inverted papilloma in the urinary bladder with special reference to its malignant potential. A 77-year-old male patient complaining of microhaematuria was subjected to cystoscopic examination, which showed a non-papillary pedunculated tumour at the postero-lateral wall, and was treated with transurethral resection. The histological findings of the specimen were compatible with inverted papilloma of the urinary bladder, except for the presence of low grade dysplastic changes in the tumour nuclei. We revealed the malignant potential of this tumour, analyzing and evaluating nuclear DNA content, proliferating cell nuclear antigen (PCNA) as well as p53 expression.

Multilocular spermatocele: a case report.

We describe a case of a multilocular spermatocele. Ultrasound examination revealed several cystic spaces at the head of the left epididymis. Epididymal tumor could not be excluded, and therefore surgical exploration was performed. Histopathological examination of the specimen revealed a multilocular spermatocele arising from the rete testis. Most spermatoceles remain small and rarely present marked clinical problems. but they are occasionally large, and may simulate a solid tumor.

Preliminary results of concurrent methotrexate, cisplatin and radiation treatment for locally advanced urothelial cancers.

Ten patients with invasive bladder cancer and one with locally advanced renal pelvic cancer were treated with concurrent methotrexate, cisplatin and radiotherapy. Methotrexate 30 mg/m2 was administered intravenously on the day of the initiation of radiotherapy and cisplatin 70 mg/m2 on the second day. The number of chemotherapy cycles delivered was 1 in 7 patients and 2 in 4. The median dose of radiation was 50 Gy. Of 11 patients, 7 (64%) achieved a partial response and 4 had no change in disease. The median duration of response was 16 months for patients with a partial response. Six patients with a partial response (55%) are alive for a median of 22.5 months and 2 of 4 with no change are alive for 4 and 15 months, respectively. Leukopenia less than 3000 cell/mm3 was observed in 4 (36%) and thrombocytopenia less than 100,000 cells/mm3 in 3 (27%). Local control could be achieved safely with concurrent methotrexate, cisplatin and radiation therapy in patients with locally advanced urothelial cancer who were unsuitable for surgery.

Condyloma acuminatum in a 3-year old girl.

We report the case of 3-year-old girl with condyloma acuminatum. She was brought to our clinic with pruritus, painful urination and four discharge and treated with electrocautery. Histological examination revealed acanthosis, nuclear basophilic inclusions and vacuolar degeneration. In this case, transmission of the human papilloma virus might have occurred during close, non-sexual contact with the infected mother, and the depressed immune response associated with atopic dermatitis appears to have played an important role in the development of the condyloma acuminatum infection.