Yotsuo Higashi

Prognostic model for predicting survival after palliative urinary diversion for ureteral obstruction: analysis of 140 cases.

PURPOSE We identified patients with ureteral obstruction likely to benefit from palliative urinary diversion so that they can be advised appropriately. MATERIALS AND METHODS A total of 140 patients with obstructive nephropathy secondary to advanced incurable malignant disease underwent percutaneous nephrostomy urinary diversion. Several variables were investigated including sex, age, type of primary malignancy, events related to malignant dissemination (metastasis, ascites and pleural effusion), number of events related to malignant dissemination, degree of hydronephrosis, location of obstruction, interval from initial diagnosis of bilateral hydronephrosis to percutaneous nephrostomy, and serum creatinine, hemoglobin and serum albumin levels before nephrostomy. RESULTS Median overall survival was 96 days (range 2 to 1,283). The 1, 6 and 12-month survival rates were 78%, 30% and 12%, respectively. On multivariate analysis the number of events related to malignant dissemination (3 or more), degree of hydronephrosis (grade 1 or 2) and serum albumin before nephrostomy (3 gm/dl or less) were significantly associated with a short survival time. The patients were divided into 3 risk groups of favorable-0 risk factors (34 patients), intermediate-1 risk factor (60) and poor-2 or 3 risk factors (41). There were significant differences in the survival profiles of the 3 risk groups (p <0.0001). The 6-month survival rates for the favorable, intermediate and poor risk groups were 69%, 24% and 2%, respectively. CONCLUSIONS The current stratification model may represent a useful tool for clinicians treating patients with ureteral obstruction due to advanced cancer.

Yolk sac tumor but not seminoma or teratoma is associated with abnormal epigenetic reprogramming pathway and shows frequent hypermethylation of various tumor suppressor genes

Germ cell tumors (GCTs) are thought to arise from primordial germ cells (PGCs) that undergo epigenetic reprogramming: erasure of the somatic imprint in the genital ridge, and re‐establishment of the sex‐specific imprint at gametogenesis in the developing gonad. Previous studies suggested that GCTs show epigenetic patterns reflecting the reprogramming process of PGCs; however, epigenetic alterations of imprinted genes and their relationship with the methylation status of tumor suppressor genes (TSGs) have not been comprehensively studied. We analyzed the methylation status of the H19 and SNRPN differential methylated regions (DMRs) and the promoter region of 17 TSGs, and the expression status of H19, IGF2 and SNRPN in 45 GCTs, and found that 25 and 20 were in the normal and abnormal reprogramming pathways, respectively, defined on the basis of the methylation status of the two DMRs and the anatomical tumor site. The methylation pattern of the H19 and SNRPN DMRs was total erasure in seminomas, mostly physiological in teratomas, and various in yolk sac tumors. There were no correlations between the methylation status of the H19 DMR and mono‐ or biallelic expression of H19 or IGF2. Furthermore, we found that yolk sac tumors had a higher number of methylated TSGs than seminomas (P < 0.001) teratomas (P = 0.004) or other childhood tumors. While TSG methylation was known to have prognostic implications in various cancers, it did not affect the outcomes of patients with yolk sac tumor, suggesting that mechanisms of TSG methylation may be different between yolk sac tumor and other cancers. (Cancer Sci 2009; 100: 698–708)

Risk stratification for bladder recurrence of upper urinary tract urothelial carcinoma after radical nephroureterectomy

To identify risk factors and develop a model for predicting recurrence of upper urinary tract urothelial carcinoma (UTUC) in the bladder in patients without a history of bladder cancer after radical nephroureterectomy (RNU).

Young Age as Favorable Prognostic Factor for Cancer-specific Survival in Localized Renal Cell Carcinoma

OBJECTIVES To evaluate the prognostic effect of age in patients with localized renal cell carcinoma (RCC) and investigate the incidence of Xp11 translocation RCC in young patients who developed recurrence. METHODS From 1990 to 2007, 2403 Japanese patients underwent nephrectomy for presumed RCC at 9 institutions. Of those, 1143 patients had localized RCC (Stage pT1-2N0M0). Their clinical data were retrospectively reviewed. In the present study, 131 patients (11%) were considered young (≤45 years at diagnosis). In the young patients with recurrence, the nephrectomy specimens were immunostained with TFE3 to determine the incidence of Xp11 translocation RCC. RESULTS During the median follow-up of 47 months, 3 cancer deaths (2.2%) occurred among young patients and 51 (5.0%) among older patients. The 5-year cancer-specific survival (CSS) rate was significantly better for the younger patients than for the older patients (P = .049). Multivariate analysis showed that age was significantly associated with CSS, as were the pathologic T stage, tumor grade, and symptoms at diagnosis. The hazard ratio of young age was 0.31 (95% confidence interval 0.077-0.87). The recurrence-free survival curves revealed no difference between these 2 groups. Of the 74 patients with recurrence, the CSS after recurrence was significantly better in the younger patients than in the older patients (P = .0010). Of the 8 young patients with recurrence, 4 had Xp11 translocation RCC, and 3 survived for >5 years after recurrence. CONCLUSIONS Compared with the older patients, the young patients with RCC had similar recurrence-free survival rates but better CSS rates. This might have been because significant numbers of the young patients had Xp11 translocation RCC.

Actinomycosis of Urachal Remnants

We report a case of urachal actinomycosis. The patient presented with complaints of micturition pain and a lower abdominal mass. Computerized tomography and an echogram showed the mass extending from the dome of the bladder to just beneath the rectus muscle. Exploration revealed a hard mass in the urachal cord, which was near the dome of the bladder and extended to the umbilicus. The mass and urachal cord were resected, and histopathological examination revealed actinomycosis of the urachal remnants.

Equivalent survival and improved preservation of renal function after distal ureterectomy compared with nephroureterectomy in patients with urothelial carcinoma of the distal ureter: A propensity score-matched multicenter study

To investigate the oncological and functional outcome of distal ureterectomy compared with nephroureterectomy in the management of distal ureteral urothelial carcinoma.

Secondary Treatment Failure without Anti-human Chorionic Gonadotropin Antibody in a Patient with Kallmann Syndrome

A 29‐year‐old man with Kallmann syndrome suddenly developed decreased semen volume, azoospermia, and facial hair loss after 11 years of successful human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG) treatment. Anti‐hCG antibody was not detected in the patients serum. A high serum level of luteinizing hormone (LH) with nasal LH‐releasing hormone analogue administration failed to increase serum testosterone to a sufficient level. Testosterone injection after cessation of hCG and hMG therapy was able to improve semen volume, but not azoospermia. Resumption of hCG and hMG therapy after 6 months cessation partially restored spermatogenesis. The secondary failure of hCG and hMG therapy suggests a decrease of testicular sensitivity to LH as well as hCG.

Cardiovascular events in survivors of high-dose chemotherapy for germ cell tumors.

Abstract:  The objective was to investigate cardiovascular complications in long‐term survivors treated by high‐dose chemotherapy. We analyzed 13 previously successfully treated metastatic germ cell cancer patients. The patients ranged in age from 16 to 38 years (median: 27 years). Patients were treated by high‐dose ifosfamide, carboplatin and etoposide (ICE) or high‐dose etoposide, ifosfamide and cisplatin (VIP). In a minimal follow‐up of 48 months, the incidence of cardiovascular events and the accumulated doses of platinum were analyzed from the total amounts of cisplatin and/or carboplatin. The calculated accumulated doses of platinum ranged from 487 to 4302 mg (median: 2297 mg). Cardiovascular events were observed in two patients who received cumulative doses of more than 3000 mg of platinum. Survivors of high‐dose chemotherapy may have a risk of developing cardiovascular complications during the early phase of follow‐up. In particular, patients who have received carboplatin‐based high dose chemotherapy require careful observation.

Clinical outcome of chemoradiotherapy for T1G3 bladder cancer

Abstract:  The aim of this study was to determine the clinical outcome of a bladder‐sparing approach using chemoradiotherapy (CRT) for T1G3 bladder cancer. Between May 2000 and August 2007, 11 patients with T1G3 bladder cancer and who were negative for macroscopic residual tumor were treated by CRT after transurethral resection of bladder tumor (TUR‐Bt). Pelvic irradiation was given at a dose of 40 Gy in 4 weeks. Intra‐arterial administration of cisplatin and systemic administration of methotrexate were carried out in the first and third weeks of radiotherapy. One month after CRT, response was evaluated by restaging TUR‐Bt. For persistent tumor after CRT or tumor recurrence, patients received additional treatment. Median follow‐up was 21.2 months. Complete response was achieved in 10 of 11 patients (90.9%). Local recurrence for the entire group of 11 patients was 22.1% at both 2 and 5 years. Tumor progression was 0% at 5 years. Disease‐specific survival rates were 100% at 5 years. All of survivors retained functioning bladders. Bladder preservation by CRT is a curative treatment option for T1G3 bladder cancer and a reasonable alternative to intravesical treatment or early cystectomy.

In vitro inhibition by ketoconazole of human testicular steroid oxidoreductases

An oral antimycotic agent, ketoconazole has been demonstrated to be an inhibitor of cytochrome P-450-dependent monooxygenases. To investigate its effect on steroid oxidoreductases, in vitro studies were carried out using subcellular fractions of human testes. Ketoconazole competitively inhibited activities of 3 beta-hydroxy-5-ene-steroid oxidoreductase/isomerase and NADH-linked 20 alpha-hydroxysteroid oxidoreductase for steroid substrate and the Ki values were 2.9 and 0.9 microM, respectively. In contrast, ketoconazole inhibited neither 17 beta-hydroxysteroid oxidoreductase nor NADPH-linked 20 alpha-hydroxysteroid oxidoreductase, indicating that the two 20 alpha-hydroxysteroid oxidoreductases are distinct. Further, ketoconazole inhibited non-competitively the above enzyme activities for the corresponding cofactors of NAD and NADH. From the binding mode of ketoconazole to cytochrome P-450 and the present findings, it appears likely that the agent binds to a site which is different from that of steroids or pyridine nucleotides.