Guidelines for the medical management of pediatric vesicoureteral reflux.

Urinary tract infection is a bacterial infection that commonly occurs in children. Vesicoureteral reflux is a major underlying precursor condition of urinary tract infection, and an important disorder in the field of pediatric urology. Vesicoureteral reflux is sometimes diagnosed postnatally in infants with fetal hydronephrosis diagnosed antenatally. Opinions vary regarding the diagnosis and treatment of vesicoureteral reflux, and diagnostic procedures remain debatable. In terms of medical interventions, options include either follow-up observation in the hope of possible spontaneous resolution of vesicoureteral reflux with growth/development or provision of continuous antibiotic prophylaxis based on patient characteristics (age, presence/absence of febrile urinary tract infection, lower urinary tract dysfunction and constipation). Furthermore, there are various surgical procedures with different indications and rationales. These guidelines, formulated and issued by the Japanese Society of Pediatric Urology to assist medical management of pediatric vesicoureteral reflux, cover the following: epidemiology, clinical practice algorithm for vesicoureteral reflux, syndromes (dysuria with vesicoureteral reflux, and bladder and rectal dysfunction with vesicoureteral reflux), diagnosis, treatment (medical and surgical), secondary vesicoureteral reflux, long-term prognosis and reflux nephropathy. They also provide the definition of bladder and bowel dysfunction, previously unavailable despite their close association with vesicoureteral reflux, and show the usefulness of diagnostic tests, continuous antibiotic prophylaxis and surgical intervention using site markings.

[A Case of Non-Treated Prostate Cancer with Disseminated Intravascular Coagulopathy].

An 87-year-old man was referred to our hospital with a high suspicion of prostate cancer, because of high prostate-specific antigen (PSA) levels (1,500 ng/ml). The laboratory results showed a PSA level of 1, 411 ng/ml, platelet count of 7.5×104/µl, and fibrinogen level of 68 mg/dl. D-dimer and fibronogen degradation product (FDP) levels were >240 and >480 µg/m respectively. Based on the above results, the patient was diagnosed as having prostate cancer with disseminated intravascular coagulopathy (DIC score=8 points). The patient was immediately hospitalized and heparin was administered to treat the DIC. On the 5th day, a prostate biopsy was performed and treatment was started with combined androgen blockade (CAB) therapy. The pathology report confirmed the diagnosis of prostate cancer with a Gleason Score of 4+3. Multiple bone and lymph node metastases were found on magnetic resonance imaging, computed tomography and, bone scans. Based on the results, the prostate cancer was stage cT3 N1 M1b. The medication was changed from heparin to nafamostat mesylate on the 12th day, due to the presence of DIC with the malignancy. After successful treatment with CAB, denosumab, and thrombomodulin alpha, the DIC levels improved (DIC score=3 points), and the PSA levels decreased to 51.5 ng/ml on the 47th day. DIC has been known to occur during treatment for prostate cancer ; however, cases of DIC with prostate cancer without any treatment are rare.

Effects of eicosapentaenoic acid on biochemical failure after radical prostatectomy for prostate cancer.

AIM: To study the effects of eicosapentaenoic acid (EPA) on prostate-specific antigen (PSA) failure in prostate cancer patients who underwent prostatectomy. PATIENTS AND METHODS: Sixty-two prostate cancer patients whose PSA levels were less than 0.2 ng/ml 3 months after surgery were randomized to either an EPA group (n=32) or a control group (n=30). EPA (2.4 g/day) was administered in the EPA group for 2 years. PSA was measured every two months. RESULTS: The EPA concentration increased but the docosahexaenoic acid concentration decreased significantly (P<0.001) in erythrocytes. The PSA recurrence rates during a mean follow-up of 53.8 months were not different between the two groups (p=0.16). CONCLUSION: A longer and/or larger intervention or docosahexaenoic acid supplementation might be necessary to identify significant preventive effects of mega-3 polyunsaturated fatty acids on PSA recurrence.

Short-term effects of crossover treatment with silodosin and tamsulosin hydrochloride for lower urinary tract symptoms associated with benign prostatic hyperplasia.

OBJECTIVES: To compare the efficacy and safety of silodosin and tamsulosin in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) by a randomized crossover method. METHODS: BPH patients with the complaint of LUTS were included in this study, and were randomly divided into two groups: a silodosin-preceding group (4 weeks of twice-daily administration of silodosin at 4 mg, followed by 4 weeks of once-daily administration of tamsulosin at 0.2 mg) or a tamsulosin-preceding group (4 weeks' administration of tamsulosin, followed by 4 weeks' administration of silodosin). No drug withdrawal period was provided when switching the drug. RESULTS: In the first treatment period, both drugs significantly improved the International Prostate Symptom Score total score, but the improvement by silodosin was significantly superior to that by tamsulosin. After crossover treatment, significant improvement was observed only with silodosin treatment. Moreover, intergroup comparison of changes revealed that silodosin showed significant improvement of straining and nocturia with first and crossover treatments, respectively, compared with tamsulosin. Silodosin also significantly improved quality of life (QOL) score in both treatment periods, while tamsulosin significantly improved QOL score only in the first treatment period. The most frequent adverse drug reaction was ejaculatory disorder with silodosin; however, the incidence of dizziness with silodosin was similar to that with tamsulosin. CONCLUSIONS: In BPH/LUTS patients, silodosin exhibits excellent efficacy in improving subjective symptoms in both initial and crossover treatment, and it appears to improve the QOL of patients.

Castleman's disease in the pararenal retroperitoneal space, which is indistinguishable from renal cell carcinoma: a case report.

A 29-year-old woman was hospitalized in our institute with the diagnosis of a right renal mass by ultrasonography on medical checkup. Computerized tomography showed a lower pole solid mass (9 cm in diameter), which was enhanced homogeneously, as well as the renal cortex in the arterial phase. The tumor was excised using radical nephrectomy based on the preoperative diagnosis of renal cell carcinoma, and thus lymph node dissection was also performed. The excised tumor was isolated from the kidney in a thin capsule, macroscopically. Postoperative pathological diagnosis revealed hyaline vascular type Castleman's disease. There was no recurrence at 1 year after the operation without any adjuvant therapy because of the complete resection.

Variation of alpha-methylacyl-CoA racemase expression in prostate adenocarcinoma cases receiving hormonal therapy.

alpha-methylacyl-CoA racemase (AMACR) is widely used as a diagnostic marker of prostate adenocarcinoma. It is also used to identify residual adenocarcinoma cells in posthormonal therapy cases. However, there have been very few studies on the relationship between hormonal therapy, which is also called androgen withdrawal therapy and AMACR expression. Here, we carried out a study on AMACR expression in paired pre- and posthormonal therapy prostate adenocarcinoma cases using an immunohistochemical method and a digital imaging system to elucidate the relationship between AMACR expression and hormonal therapy. This study showed that AMACR expression was decreased in 65 of 98 paired cases after hormonal therapy (Mann-Whitney U test, P < .05). Wilcoxon analysis also demonstrated a difference in the AMACR digital average expression in all 98 cases (P < .0001). However, this variation in AMACR expression did not seem to have any relevance to the response to hormonal therapy (P = .5386). We propose that AMACR, as a diagnostic marker, should be carefully used in posthormonal therapy cases. Further investigation of the relationship between AMACR expression and androgen or androgen receptors may provide new insight into novel preventive and curative medicine for prostate adenocarcinoma.

The effect of eicosapentaenoic acid on prostate-specific antigen.

The "Study of EPA Effects on Prostate Cancer" (SEEPC) Group has been conducting a clinical trial with patients who underwent radical prostatectomy. The main purpose of the SEEPC is to evaluate whether eicosapentaenoic acid (EPA) prevents prostate cancer (PC) recurrence. As the surrogate marker of recurrence, the prostate-specific antigen (PSA) level was measured. However, if EPA affects the PSA values independently of PC, PSA may not be a good marker of recurrence in the event of EPA treatment. Thus, in the present study, whether EPA affected the PSA values was investigated using non-PC volunteers. Twenty men, of at least 50 years of age, were recruited, mostly from hospital staff The volunteers were randomly allocated either to the EPA group or the control. The subjects in the EPA group were administered EPA-ethyl ester a dose of 2400 mg/day for 12 weeks, whereas the controls were administered none. Fasting blood samples were obtained before the start of EPA administration and 4 and 12 weeks later. The EPA concentrations in erythrocytes increased in all the subjects in the EPA group (174+/-96%) with no significant changes in the control group (8.5+/-14.0%). There were no significant differences between the two groups in the serum PSA levels, allowing the conclusion that the PSA is an appropriate surrogate marker of recurrence in prostate cancer.

Association of neuroendocrine differentiation with neoadjuvant hormone therapy effects in prostatic cancer.

Histological therapeutic effects of neoadjuvant hormone therapy (NHT) in prostatic cancer were examined, focusing on the association with neuroendocrine differentiation (NED), using 69 radical prostatectomy cases. The effects of NHT were classified into 3 grades based on the extent of tumor degeneration as observed with hematoxylin and eosin staining. NED cells in the cancer were semi-quantified into 4 grades (negative, 1+, 2+, and 3+) by immunohistochemical staining of chromogranin A (CgA). According to the therapeutic effects, the cases are divided as follows: good response in 26 patients, intermediate in 20, poor in 23. The histological therapeutic effects were significantly weaker in the CgA-positive group than the CgA-negative group (p=0.02). A close relationship between the extent of CgA expression and the histological response was also demonstrated (p=0.007). In the biopsy specimens before NHT, CgA was positive in 46% (32/69) and there was no significant difference in histological therapeutic effects between the positive and negative groups. However, the therapeutic effects were significantly weaker in 22 CgA-positive cases for both biopsy and prostatectomy specimens than in 18 CgA-negative cases for both specimens (p=0.001). In conclusion, although it seems difficult to predict the therapeutic effects of NHT using the biopsy specimens of prostatic cancer, we believe that NED is negatively associated with histological response of prostatic cancer to NHT.

Successful treatment of renal cell carcinoma with mediastinal lymph node metastasis by interleukin-2: a case report.

A 57-year-old woman presented to our hospital with macrohematuria. Renal cell carcinoma (RCC) of the left kidney with bilateral pulmonary and mediastinal lymph node metastases was diagnosed. Radical nephrectomy was performed. Pathological examination confirmed the diagnosis of RCC (pT2pN0M1), so immunotherapy was performed using interleukin-2 (IL-2). The mediastinal lymph node metastases disappeared completely after 5 months of immunotherapy. Investigation of immunological parameters showed an increase of CD8-positive T cells (CD8) and a decrease of CD14-positive cells (CD14), leading to a marked increase of the CD8/CD14 ratio. Although her pulmonary metastases are unchanged, the mediastinal metastases still show complete remission at 14 months postoperatively. The CD8/CD14 ratio may have potential as a new marker for monitoring the response of RCC to immunotherapy and selecting suitable patients for such therapy.

[Schwannoma of the kidney with severe calcification: a case report].

Schwannoma arising from the kidney is a rare benign tumor, with only 20 cases reported in the English literature. We encountered a histopathologically typical Schwannoma of the kidney in a 39-year-old woman, which was characterized by marked calcification. Radical nephrectomy was performed under the diagnosis of renal cell carcinoma. The 21 reported cases of schwannoma of the kidney, including the present case, are reviewed in detail.

[Metastatic small intestinal tumor associated with transitional cell carcinoma: a report of 2 cases and review of cases in Japan].

Transitional cell carcinoma (TCC) frequently metastasizes to lymph nodes, liver, lungs and bone. However, metastasis to the gastrointestinal tract is rare. We report two cases of bladder tumor which metastasized to the ileum. According to the literature, these are the 7th and 8th cases in Japan. Case 1: A 87-year-old man had a history of bladder tumor (TCC, grade 3, pT2bN0M0) and has transurethral resection of bladder tumor (TUR-BT) three times. Two months after the last TUR-BT, he was admitted with ileus. As computed tomography (CT) showed abdominal free air, our diagnosis was perforation of gastrointestinal tract. The patient received an operation which resected partial ileum. We found the elastic hard tumor in the ileum on the perforated lesion, which showed metastatic TCC in the ileum pathologicaly. Case 2 : A 53-year-old man visited our hospital with gross hematuria. Cystoscopy showed a non-papillary broad based tumor in the right wall of the bladder. CT showed a bladder tumor invaded into the prostate (pT4aN1M0), we performed total cyctectomy and ileal conduit after neo-adjuvant chemotherapy. During the operation, we found the tumor (2 cm in diameter) in the small intestine which was metastasized of bladder tumor.

Screening program of prostate cancer at Tokai University Hospital: characterization of prostate-specific antigen measurement.

A total of 67,214 men participated in screening for prostate cancer (PC) using serum prostate-specific antigen (PSA) from April 1996 to March 2003 at Tokai University Hospital. In 3.5% (2330 / 67,214) of the men, an elevated PSA level (> 4.0 ng/ml) was found and 68.1% (1586/2330) of these subjects were examined at our Urological Outpatient Clinic. Re-testing of PSA showed that 8.4% (133/1586) had a normal level. Needle biopsy of the prostate was performed in 45.2% (633/1453) of the remaining men. As a result, 142 PCs were found and the detection rate was 0.2% (142 / 67,214). The age of the patients with PC was over 50 years. During this period, 135 individuals with voiding dysfunction were also diagnosed as having PC. Comparison of the patients detected by screening with those found at the outpatient clinic revealed significant differences of the age (64.8 vs. 71.9 years, p < 0.0001), serum PSA level (14.6 vs. 154.9 ng/ml, p < 0.0001), and clinical stage (p < 0.0001). In conclusion, a health screening program that includes serum PSA testing is useful for detection of PC at an earlier stage and in younger individuals. We recommend that all men aged 50 years or older undergo testing for PSA to detect PC at an early stage.

Clinical Outcomes of Transurethral Enucleation with Bipolar for Benign Prostatic Hypertrophy.

OBJECTIVE: This study compared outcomes of transurethral enucleation with bipolar (TUEB) with transurethral resection in saline (TURis). METHODS: Thirty patients who underwent TURis were compared with 30 who underwent TUEB. Perioperative treatment outcomes, preoperative and 1-month postoperative International Prostrate Symptom Scores (IPSS), quality of life (QOL) index, maximum flow rate, average urinary flow, post- void residual urinary volume, and complications were compared. RESULTS: There were no significant differences in IPSS, measurements of urinary flow, or duration of catheterization. However, the improvement of QOL index after surgery was significantly greater in the TUEB group than the TURis group. The TUEB group had significantly longer surgical time, but tended to have greater enucleated tissue weight than the TURis group. There was no significant difference in enucleated tissue weight per unit time between the groups. The TUEB group also tended to have less hemoglobin decrease at postoperative day 1; this tendency was more prominent in patients with an estimated prostate volume of ≥ 50 ml. No significant differences in postoperative complications were observed. CONCLUSIONS: This study confirmed that the previously reported safety and efficacy of TUEB are comparable to those of TURis. TUEB appears especially safe for those with a large benign hypertrophic prostate.

[A case of squamous metaplasia of the ureter].

This paper reports a 73-year-old man who developed ureteral squamous metaplasia. Preoperative drip infusion pyelography showed a ureteral tumor with a major axis measuring 2.5 cm, which had a smooth surface and a broad base. Computed tomography findings suggested that the lesion might be a submucous mesodermal tumor or inverted papillary transitional cell carcinoma. Therefore, retroperitoneal laparoscopic left nephroureterectomy was performed.

Usefulness of hypoxia inducible factor-1 alpha in evaluating the prostatic adenocarcinoma viability following neoadjuvant hormone therapy.

BACKGROUND: In prostatic adenocarcinomas (PAs), the androgen up-regulates hypoxia inducible factor-1 alpha (HIF-1 alpha). It has been reported that the regulation of HIF-1 alpha would become a therapeutic strategy for PAs. This study was designed to elucidate whether or not HIF-1 alpha expression would be associated with PA recurrence after neoadjuvant hormone therapy (NHT). METHODS: The 50 radical prostatectomy specimens after NHT were examined as well as needle biopsy specimens before NHT using immunohistochemistry for HIF-1 alpha. RESULTS: The therapeutic effects of 50 cases with NHT were assessed as good (20 cases) or poor (30 cases). The recurrence of PA monitored by the serum prostatic specific antigen (PSA) levels occurred in 21 cases (42%). The hypoxic status was evaluated to be divided into two categories: weak (16 cases) or strong (34 cases). The recurrence ratio was 30% (6/20) of cases with good response and 50% (15/30) of cases with poor response (p<0.05). HIF-1 alpha expression profiles were as follows: recurrent cases, weak, 19% (4/21); strong, 81% (17/21) (p<0.05); and non-recurrent cases, weak, 41% (12/29); strong, 59% (17/29) (NS). Compared to PAs with weak HIF-1 alpha expression, PAs with strong HIF-1 alpha expression showed higher PSA levels (12.1 ng/mL vs. 25.0 ng/mL, p<0.05). CONCLUSION: HIF-1 alpha is expected to be useful for detection of the viability of PAs after NHT and also for prediction of their clinical outcome. In addition, the expression may contribute to histological identification of the carcinoma cells.

Clinicopathological factors predicting recurrence of N0M0 renal cell carcinoma: a case series analysis of one facility.

BACKGROUND: Although many factors have been reported as predictors of the recurrence of renal cell carcinoma (RCC), none of the factors are consistent among different studies. In the study presented here, the potential clinicopathological predictors of the recurrence of N0M0 RCC were examined. METHODS: A total of 201 patients who underwent nephrectomy for N0M0 RCC were examined to determine the pathological tumor stage (pT stage), pathological tumor grade of malignancy (tumor grade), symptoms, and tumor size. RESULTS: RCC recurred in 29 patients (14.4%), 50% of whom developed new tumors within 24 months after nephrectomy. The disease-free 3- and 10-year survival rates declined as the pT stage and tumor grade increased: these rates were, respectively, 98.6% and 86.5% for pT1a; 93.7% and 87.9% for pT1b; 100% and 100% for pT2; 78.6% and 58.0% for pT3a; and 88.9% and 16.7% for pT3b. Significant differences in the recurrence rate were noted between pT3 and pT1 or pT2, as well as between grade 3 disease and grade 1 or grade 2 tumors. Multivariate analysis showed that a combination of the pT stage, grade, and presence of symptoms was useful for predicting the recurrence of RCC. CONCLUSION: The present study showed that patients undergoing nephrectomy for N0M0 RCC should be followed-up carefully for 2 years postoperatively with special attention to high pT stage, high grade, and the development of symptoms.