Eiichiro Takaoka

Successful management by provocative angiography and endovascular stent of Ureteroarterial fistula in a patient with a long-term indwelling ureteral stent.

We present the clinical course of a ureteroiliac arterial fistula in a patient who had been managed by ureteral stenting for 8 years for severe ureteral stricture after abdominoperineal resection with pelvic irradiation for advanced rectal cancer. A multidisciplinary team approach including provocative angiography and an endovascular stent saved the life of the patient. Ureteroarterial fistula is a rare complication of a long-term indwelling ureteral stent that is potentially fatal unless a prompt diagnosis and adequate therapy are provided. Heightened awareness and a high index of suspicion for this condition are required to make an early diagnosis.

Risk Factors for Intravesical Recurrence in Patients with High-grade T1 Bladder Cancer in the Second TUR Era

OBJECTIVE We aimed to elucidate risk factors for intravesical recurrence of high-grade T1 bladder cancer in the second transurethral resection era. METHODS The analysis included 73 patients with high-grade T1 bladder cancer on initial transurethral resection. The median follow-up period was 49.2 months. Recurrence-free survival, progression-free survival and risk factors related to the presence of residual tumors or recurrence-free survival were statistically analyzed. RESULTS The pathological findings for second transurethral resection were pT0 36 (49%), pTis/a 21 (29%), pT1 13 (18%) and pT2 3 (4%), respectively. The risk factor for residual tumors at second transurethral resection was the presence of concomitant carcinoma in situ at the initial transurethral resection (P < 0.01). The bladder was preserved in all 57 patients with pT0/is/a tumors on second transurethral resection, and 43 patients (75%) received intravesical BCG therapy. Of these patients, 3-year recurrence-free survival and 3-year progression-free survival rates were 81 and 96%, respectively. In addition, the presence of pTis/a residual tumors on second transurethral resection had a significant impact on the recurrence. Five of the 13 patients with pT1 on second transurethral resection were immediately treated by radical cystectomy or radiation therapy combined with chemotherapy, and two (25%) of the eight who were treated by intravesical BCG therapy had progression including distant metastasis. CONCLUSIONS High recurrence-free survival and progression-free survival were achieved by a second transurethral resection and intravesical BCG therapy in the patients with pT0/is/a on the second transurethral resection. In this group, the residual tumors at second transurethral resection are risk factors for intravesical recurrence.

Concurrent Urothelial Carcinoma in the Renal Pelvis of an Allograft Kidney and Native Recipient Bladder: Evidence of Donor Origin

A 44-year-old woman was admitted to the hospital for asymptomatic gross hematuria. At the age of 28, she underwent transplantation of a kidney from her father for end-stage renal disease secondary to rapidly progressive glomerulonephritis. She resumed peritoneal dialysis when the allograft kidney stopped functioning at the age of 42. Dialysis was continued for the next 2 years, when the hematuria occurred and she was readmitted. Radiologic evaluation and transurethral resection of the bladder tumor revealed a tumor of the renal pelvis of the allograft kidney (cT3N0M0) and multiple bladder tumors (cT1N0M0). Total cystectomy and allograft nephroureterectomy were performed. Histopathological examinations revealed high grade urothelial carcinoma in the renal pelvis of the allograft kidney (pT3) and native bladder (pT1). Fluorescence in situ hybridization of both specimens demonstrated that the renal pelvic tumors and bladder cancer possessed XY karyotypes. These results indicated that the urothelial carcinoma developed de novo in the renal pelvis of the allograft kidney and was implanted into the recipients native bladder.

Cavernous hemangioma mimicking a cystic renal cell carcinoma.

A 69-year-old man was hospitalized for treatment of a left renal tumor. The tumor had originally been demonstrated as a simple renal cyst 4 years before. However, the size of the tumor decreased, and at the time of hospitalization, the tumor showed a solid, papillary component that was enhanced by contrast medium on computed tomography (CT) and had high signal intensity on T2-weighted magnetic resonance imaging (MRI). We diagnosed this tumor as a cystic renal cell carcinoma of the left kidney, cT1aN0M0, arising from the epithelium of a renal cyst, and performed a left partial nephrectomy. The pathological diagnosis was cavernous hemangioma of the left kidney. Generally, it is difficult to diagnose a cavernous hemangioma of the kidney preoperatively. This case is unusual because the configuration of this tumor changed within a few years. When we find a renal cyst with a solid component, renal cavernous hemangioma arising from the cyst wall should be considered in the differential diagnosis, and a conservative surgical approach should be considered.

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 Acute Adrenal Insufficiency Unmasked During Sunitinib Treatment for Metastatic Renal Cell Carcinoma

Sunitinib has recently become a standard treatment for metastatic renal cell carcinoma. However, various adverse events have been reported. We present the first case of clinically evident adrenal insufficiency during sunitinib therapy. A 72-year-old man began sunitinib therapy for bilateral lung and adrenal metastases of renal cell carcinoma. His adrenocorticotrophic hormone level was 93.6 pg/ml (7.2-63.3 pg/ml) before sunitinib treatment, indicating that subclinical adrenal insufficiency already existed. Fatigue, which is a frequently seen adverse effect of sunitinib treatment, emerged acutely on Day 24 of the second cycle. Adrenocorticotrophic hormone and free T4 were high and thyroid-stimulating hormone was suppressed. Under the clinical diagnosis of acute adrenal insufficiency with thyrotoxicosis, a low dose of steroid was administered. Fatigue was completely ameliorated by the following morning, although free T4 was still high and thyroid-stimulating hormone was still low. Therefore, hypermetabolism due to thyrotoxicosis unmasked adrenal insufficiency in our case. Physicians should be aware of this rare but potentially fatal complication when severe acute fatigue develops in patients with subclinical adrenal insufficiency.

Nerve growth factor‐dependent hyperexcitability of capsaicin‐sensitive bladder afferent neurones in mice with spinal cord injury

What is the central question of this study? Nerve growth factor (NGF) is reportedly a mediator inducing urinary bladder dysfunction. Is NGF directly involved in hyperexcitability of capsaicin‐sensitive C‐fibre bladder afferent pathways after spinal cord injury (SCI)? What is the main finding and its importance? Neutralization of NGF by anti‐NGF antibody treatment reversed the SCI‐induced increase in the number of action potentials and the reduction in spike thresholds and A‐type K+ current density in mouse capsaicin‐sensitive bladder afferent neurones. Thus, NGF plays an important and direct role in hyperexcitability of capsaicin‐sensitive C‐fibre bladder afferent neurones attributable to the reduction in A‐type K+ channel activity in SCI.

MP85-03 THE THERAPEUTIC EFFECT OF TRPV4 ACTIVATION IN THE BLADDER ON UNDERACTIVE BLADDER IN RATS WITH PELVIC NERVE CRUSH

RESULTS: There were no significant differences in micturition pressure, threshold pressure, voided volume, post-void residual, bladder capacity or voiding efficiency among 3 groups. The number of non-voiding contractions (NVCs) per a voiding cycle in groups B and C were significantly lower than that of group A. NGF levels of the bladder mucosa and spinal cord of SCI mice (group A) were significantly increased compared with spinal intact mice. Two-weeks (group C), but not one-week (group B), anti-NGF treatment significantly decreased bladder mucosal and spinal NGF expression. The mRNA levels of TRPA1 and TRPV1 were increased in SCI mice compared to spinal intact mice, and significantly decreased after both 1 week and 2 weeks of anti-NGF treatment. CONCLUSIONS: One-week and 2-week treatments similarly improved NVCs in association with the reduction of the expression of TRPA1 and TRPV1 in L6/S1 DRG although 2-weeks anti-NGF treatment was required to significantly decrease bladder mucosal and spinal NGF. Thus, NGF overexpression is likely to play a significant role in storage dysfunction to induce DO in SCI mice.

MP45-06 BLADDER UROTHELIAL AND AFFERENT DYSFUNCTIONS UNDERLYING BLADDER OVERACTIVITY IN RATS WITH CHEMICALLY INDUCED PROSTATIC INFLAMMATION

histology, immunohistochemistry, western blot analyses and quantitative PCR. In vitro effects of GHRH were tested on human prostate epithelial (BPH-1) and stromal (WPMY-1) cell lines. RESULTS: Carrageenan-induced prostatitis (CIP) produced a 73.2% increase in weights of the ventral prostate lobes which was reduced by 19.2% in rats treated with MIA-690. Vimentin staining showed thickening of the stromal compartment which effect was also suppressed by GHRH antagonists. Western blot analysis demonstrated an increase in GHRH, COX2 and TGF-b1 levels by inflammation and suppression by MIA-690. Prostatic IGF-1 levels measured by ELISA were increased by 65% in CIP and were suppressed to control level by GHRH antagonist. A qPCR array analysis of genes related to EMT revealed upregulation in several genes including collagens, matrix metalloproteinase 9, Snail1, TGF-b1 and vimentin by inflammation and downregulation by treatment with MIA-690. In vitro, GHRH stimulated the phosphorylation of EGF and IGF receptors and upregulated the level of TGF-b1 in BPH-1 cells but had no measurable effects on WPMY-1 stromal cells. CONCLUSIONS: Our current findings strongly indicate that GHRH is a key molecular player in inflammation-induced prostate enlargement via its direct action on epithelial cells. The effect of GHRH antagonists on stromal cells may be the consequence of their effect on epithelial growth factor production. Consequently, GHRH antagonists could be clinically useful to treat early and advanced stages of BPH due to their anti-proliferative and anti-inflammatory activities.

PD19-10 P38 MITOGEN-ACTIVATED PROTEIN KINASE INHIBITOR REDUCES HYPEREXCITABILITY OF CAPSAICIN SENSITIVE BLADDER AFFERENT NEURONS IN MICE WITH SPINAL CORD INJURY

cystitis(KC). However, the actual pathophysiology and pathogenesis were still unclear. The aim of current study is to investigate the neurotrophin expression and the fibrogenesis pathway in the KC urothelium. METHODS: The KC patients who were treated at our hospital were enrolled into this study. They were divided into two groups: mild KC and severe KC. The mild KC group means patient underwent cystoscopic hydrodistention and the severe KC group means patients was treated with partial cystectomy with augmentation enterocystoplasty. Bladder specimens were taken during the procedures and were investigated for sensory receptors and related protein including with Western blotting. Western blotting with quantification was used to investigate the expression of neurotrophin growth associated protein 43 (GAP-43), nerve growth factor (NGF) and its receptor tropomyosin receptor kinase A (TrkA) and Brain-derived Neurotrophic Factor (BDNF) and its receptor tropomyosin receptor kinase B (TrkB). The fibrogenic cystokine transforming growth factor beta (TGF-b) was also investigated. Three Bladder specimens from patients with bladder cancer and underwent radical cystectomy were also obtained as normal control. RESULTS: A total of 19 KC patients(mild:6 and severe:13) and 3 normal controls were enrolled. Three groups revealed difference in GAP43,TGF-b, TrK-A and BDNF and the similar outcomes revealed between normal and severe KC group. In compared with mild KC and severe KC, there were only TGF-b and TrK-A revealed statistical differences(Table 1 and Figure 1). CONCLUSIONS: Among the neurotrophin and its receptors we had investigated, GAP-43, TrK-A and BDNF were significantly higher in severe KC group. The TGF-b was also higher in the severe KC bladder than that in mild KC and control. Trk-A, GAP-43, BDNF and TGF-b may play an important role in the pathogenesis in KC, and may lead to disease progress to severe KC. Source of Funding: none