[A Case of Proliferative Cystitis Discovered as Protruding Lesion during Inspection of Secondary Infertility].

A 42-year-old man visited our hospital complaining of secondary infertility. An abdominal ultrasonography screening incidentally revealed a protruding lesion in the bladder. As the lesion extended from the prostatic urethra and bladder neck, there was a possibility of ejaculation dysfunction after resection of the lesion. Therefore, with the patient's informed consent, sperm cryopreservation was conducted for fertility preservation, and subsequently histological examination was performed by partial transurethral resection of bladder tumor. The pathological findings were proliferative cystitis including all three subtypes (glandularis, cystica, and papillary). Cyclooxygenase-2 immunostaining was positive in cytoplasm; weakly positive in cystic and papillary lesions, and strongly positive in glandular lesions. According to a literature review of massive proliferative cystitis, the patient was the 77th case in Japan. Novel postoperative immunological pharmacotherapies with cyclooxygenase-2 inhibitors have been introduced in recent years.

Risk factors for loss to follow-up during active surveillance of patients with Stage I seminoma.

OBJECTIVE: To elucidate the patterns and risk factors for loss to follow-up during active surveillance for Stage I seminoma. METHODS: A total of 425 cases with Stage I seminoma underwent radical orchiectomy from 1985 to 2006 at 25 Japanese institutions, including 22 community hospitals and 3 university hospitals. The post-orchiectomy management selected was active surveillance for 186 patients, adjuvant radiotherapy for 182 patients and chemotherapy for 57 patients. The Kaplan-Meier method was used to estimate the recurrence-free survival and loss to follow-up rate. The risk factors for loss to follow-up were examined using Cox's proportional hazards model with multiple variables. RESULTS: The 2-, 5- and 10-year loss to follow-up rates in the active surveillance group were 14.2, 37.8 and 71.3%, respectively, which were not significantly different in comparison with those in the active surveillance and adjuvant radiotherapy or chemotherapy groups. With regard to the active surveillance group, the multivariate analysis demonstrated that patients younger than 36 years at diagnosis, patients diagnosed since 2000 and patients treated at hospitals that enrolled more than 10 cases had a significant risk for loss to follow-up. No significant correlation between the loss to follow-up rate and pathological risk factors such as tumor size (≤4 versus >4 cm) and rete testis invasion (presence versus absence) was shown. CONCLUSIONS: The loss to follow-up rates beyond 5 years were unsatisfactorily high during active surveillance. Further approaches to improve the quality of active surveillance are needed, especially for high-risk patients such as those of younger age.

Assessment and management of renal impairment in chemotherapy for urogenital cancer.

The method of diagnosing chronic kidney disease by simple estimated glomerular filtration rate equations has demonstrated a high prevalence of chronic kidney disease among the genitourinary cancer patients. Approximately 30-50% of urothelial cancer patients have Grade 3 chronic kidney disease before chemotherapy, and the rate increases to around 80% in upper urinary tract cancer patients who have undergone radical surgery. Several gold-standard treatments, including cisplatin for urothelial/testicular tumors and anti-vascular endothelial growth factor therapy for kidney cancers, are known to be associated with the development of renal impairment. However, which renal function assessments are best to select a chemotherapy regimen remain unknown. Most testicular tumor patients are cured by intensive combined chemotherapy with cisplatin, but chemotherapy can induce chronic kidney disease in testicular cancer survivors. The prevalence of Stage 3 chronic kidney disease among the testicular cancer survivors is between 10 and 20%. Thus, the estimated glomerular filtration rate assessment is a useful tool for monitoring the development of chronic kidney disease among the cancer survivors, and assessment of renal function is mandatory before the treatment of these genitourinary cancer patients.

Oncological outcomes of metastatic testicular cancers under centralized management through regional medical network.

OBJECTIVE: To investigate the dose intensity of induction chemotherapy and oncological outcomes of metastatic testicular cancer under centralized management through a regional medical network. MATERIALS AND METHODS: We retrospectively analyzed the outcomes of 86 metastatic testicular cancer patients who were given induction chemotherapy at Tsukuba University Hospital and four branch hospitals between January 2000 and November 2010. Principally, management of patients with poor-prognosis disease and patients having risk factors for bleomycin, etoposide and cisplatin were referred to Tsukuba University Hospital before chemotherapy. For high-risk groups, etoposide and cisplatin or etoposide, ifosfamide and cisplatin was used as an alternative to bleomycin, etoposide and cisplatin. RESULTS: Overall, 56 and 30 patients were treated at Tsukuba University Hospital and branch hospitals, respectively. Forty-seven, 18 and 21 patients were classified with good-, intermediate- and poor-prognosis disease, respectively, according to the International Germ Cell Cancer Collaborative Group criteria. Eighteen of the 21 patients (86%) with poor-prognosis disease were treated at Tsukuba University Hospital from the beginning of induction chemotherapy. Induction chemotherapy with a high relative dose intensity was possible in most patients. The average relative dose intensity of each drug was >0.96. Treatment procedures other than induction chemotherapy were efficiently centralized; 74% of post-chemotherapy surgery and all second-line or subsequent chemotherapies were performed at Tsukuba University Hospital. The 5-year overall survival rates of the good-, intermediate- and poor-prognosis groups were 97, 93 and 84%, respectively. CONCLUSIONS: Induction chemotherapy with high relative dose intensity, post-chemotherapy surgery and salvage chemotherapy was accomplished efficiently through centralization of management. Oncological outcomes were excellent, especially in patients with poor-prognosis disease, whose 5-year OS reached 84%.

Risk factors for chronic kidney disease after chemotherapy for testicular cancer.

OBJECTIVE: To elucidate the patterns of and risk factors for deterioration of renal function after chemotherapy in metastatic testicular cancer survivors using the estimated glomerular filtration rate. METHODS: A total of 96 patients who were treated with cisplatin-based chemotherapy for metastatic testicular cancer between January 1981 and December 2010 were enrolled in this study. The estimated glomerular filtration rate was based on the serum creatinine concentration using the formula of the Japanese Society of Nephrology. Risk factors for chronic kidney disease were examined by multivariate logistic-regression analysis. RESULTS: The median follow-up period was 70 months (range 15-342). The median pretreatment estimated glomerular filtration rate was 98 mL/min/1.73 m(2) (range 44-216), and it gradually decreased for 1 year after the end of chemotherapy, although there was no significant change in estimated glomerular filtration rate beyond 1 year. One year after chemotherapy, 22 of 96 patients (23%) showed chronic kidney disease (less than 60 mL/min/1.73 m(2) estimated glomerular filtration rate). The multivariate analysis showed that the patients with mild renal damage (estimated glomerular filtration rate 60-89 mL/min/1.73 m(2) ) and elevated blood pressure (higher than 130/80 mmHg) before treatment had a significant risk with odds ratios of 2.63 (95% confidence interval 1.09-6.73) and 4.22 (95% confidence interval 1.45-12.6), respectively. CONCLUSIONS: Close monitoring of renal function is important for at least 1 year after chemotherapy for testicular cancer, especially in patients having elevated blood pressure and/or mild renal damage before chemotherapy.

Management of ureteral obstruction in advanced testicular tumor with lymph node metastasis.

OBJECTIVE: Ureteral obstruction is one of the complications of testicular tumor with retroperitoneal lymph node metastasis that requires ureteral stenting for management. We elucidated the clinical courses of ureteral obstructions and changes in renal functions in patients with indwelling ureteral stenting. METHODS: The medical records of 56 patients who were treated for metastatic testicular tumors by chemotherapy at a single institute between 2002 and 2010 were retrospectively reviewed. RESULTS: Among 56 patients, 12 patients needed ureteral stenting before chemotherapy. The proportion of patients requiring ureteral stenting was significantly higher in seminoma than non-seminoma (47 and 12%, respectively, P < 0.05). The ureteral stent was removed after chemotherapy or retroperitoneal lymph node dissection in all patients, except for one patient who died of cancer during chemotherapy. At retroperitoneal lymph node dissection, ureters were spared in three patients, a partial ureterectomy was needed in one patient, and no case underwent adjunctive nephrectomy. These 11 patients presented no local and distant recurrence at median follow-up of 44 months. Ureteral stenting increased the estimated glomerular filtration rate to more than 60 ml/min before chemotherapy in all patients, but it decreased to <60 ml/min in 6 of 11 patients after chemotherapy. CONCLUSIONS: Ureteral obstruction due to testicular tumor was relieved after chemotherapy or retroperitoneal lymph node dissection. Ureteral stenting was effective to improve renal function before chemotherapy, although we should pay special attention to deterioration of renal function during or after chemotherapy.

[A case of Kallmann syndrome: usefulness of the aging male's symptoms rating scale for assessment of subjective symptoms].

We report a case of Kallmann syndrome in which the aging male's symptoms rating scale (AMS) was useful for assessment of subjective symptoms. A 30-year-old male was admitted to Tsukuba University Hospital with a complaint of delayed puberty in May 2003. He presented with hypogonadism, gynecomastia and anosmia. The plasma levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone were very low. However, the LH-releasing hormone test and human chorionic gonadotropin (hCG) loading test identified normal function of pituitary and Leydig cell. After 12 months of treatment with hCG and human menopausal gonadotropin (hMG), the amount of pubic hair and the volume of testes had increased as well as the level of serum testosterone. The total score of AMS after treatment has been improved from 39 to 20 as compared with that before treatment.

[Bilateral uretero-common iliac arterial fistula with long term uretelal stent: a case report].

A 37-year-old man underwent Miles' operation and adjuvant irradiation therapy for rectum cancer in 1999. The patient suffered from bilateral ureteral stricture after the previous therapies. Bilateral double-J ureteral stents were inserted and exchanged at regular intervals. Four years after the start of ureteral stenting, he complicated with gross hematuria and dysuria. When the right double-J stent was exchanged, massive bleeding from external opening of urethra was observed. Retrograde pyelography showed right uretero-iliac arterial fistula. Since endovascular treatment with covered stents had failed, we performed right common iliac artery embolization and femoral-femoral artery bypass. Two days after the operation, gross hematuria developed again. When the left ureteral stent was exchanged, active bleeding from the external meatus of urethra was revealed. Angiography showed extravasation from left common iliac artery. We diagnosed left uretero-iliac arterial fistula. Although we tried endovascular treatment with covered stent that was made of artificial vessel graft and metallic stent, thromboembolism was occurred in the covered stent. Finally, right axillo-femoral artery bypass was indicated. The last treatment achieved long-term good control of uretero-arterial fistula. The present case shows that uretero-arterial fistula is a serious complication of long-term ureteral stenting, especially in the case of post pelvic surgery and irradiation.

Systemic transduction of p16INK4A antitumor peptide inhibits the growth of MBT-2 mouse bladder tumor cell line grafts.

p16(INK4a) (p16), a key molecule in bladder tumor development, inhibits the activities of cyclin-dependent kinases (CDKs) and maintains the retinoblastoma protein (pRb) in its active hypophosphorylated state. Following the finding that the p16 antitumor peptide dramatically inhibits the growth of aggressive leukemia/lymphoma through the restoration of p16 function using the Wr-T peptide transporter system, in this study, we developed a systemic therapy using mouse­p16 peptide (m­p16) in subcutaneous p16­null mouse bladder tumors. In vitro analysis showed that the growth of p16­null bladder tumor cells and the hyperphosphorylation of their pRbs were inhibited by p16 transduction in a concentration­dependent manner. In an animal model, p16­null MBT­2 cells were injected subcutaneously into KSN/SKC nude mice. The systemic delivery of the m­p16 peptide using Wr­T by cardiac injection significantly inhibited the growth of solid MBT­2 tumors compared with the control phosphate­buffered saline (PBS) injection. Histological examination by TUNEL staining revealed that apoptosis was increased and pRb phosphorylation was inhibited. Thus, the systemic peptide delivery of p16 restores the hypophosphorylation of pRb and may be a useful tool for the treatment of bladder tumors.

Retroperitoneal extragonadal germ cell tumor in a patient with Klinefelter's syndrome.

A 22-year-old man was diagnosed with retroperitoneal seminoma associated with Klinefelter's syndrome. The tumor was 14 x 12 cm in size and surrounded the superior mesenteric artery. He received induction chemotherapy with bleomycin, etoposide and cisplatin (BEP) followed by salvage chemotherapy with paclitaxel, ifosfamide and cisplatin (TIP). The tumor considerably decreased in size and remains as a poorly defined plaque. At the time of writing, he is being followed closely and is free from progression.