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Spermatocytic seminoma (SS) is a rare testicular germ cell tumor (TGCT), occurring exclusively in the testes. Diagnosis of SS is important because, unlike other testicular tumors, SS must be treated by orchiectomy alone without further adjuvant therapy owing to its inability to metastasize. However, an accurate diagnosis of SS is often difficult given its rarity and the lack of a reliable marker. We report the occurrence of SS in a 92-year-old man—one of the oldest SS patients reported thus far. The patient presented with a painful right scrotal mass, which had been present for 6 months. A computed tomography scan revealed a testicular mass. There was no significant increase in the serum levels of alpha-fetoprotein (AFP) or human chorionic gonadotropin (hCG). A right orchiectomy was performed, which showed a well-circumscribed white-gray mass. A histological examination revealed sheets of non-cohesive cells with little intervening stroma. The tumor consisted of small, medium, and large cells with frequent mitoses, which is suggestive of SS. Whereas common TGCT markers including AFP, hCG, CD30, and placental alkaline phosphatase were all negative, nuclear reactivity for SALL4, a new TGCT marker, and positivity for CD117 (c-kit) finally helped establish the diagnosis of SS. We conclude that SALL4 immunostaining can be helpful for the diagnosis of TGCT when tumors are negative for conventional TGCT markers.

A rare case of epididymal spindle cell sarcoma in a 68-year-old man is described. The patient was admitted to our hospital with a painless, left intrascrotal mass that had been present for 3 months. Computed tomography revealed a left paratesticular tumor and inguinal lymph node swelling. With a diagnosis of a paratesticular malignant tumor, left high inguinal orchiectomy and lymphadenectomy were performed. Histopathological and immunohistochemical examinations revealed spindle cell sarcoma with a positive surgical margin of the lymph node. The patient was treated with 54 Gy of external beam radiation therapy to the scrotum and the inguinal lymph node. Since the patient’s general condition was poor after recurrence, systemic chemotherapy could not be performed. The patient died 10 months after initial diagnosis.

In this study, hemoglobin vesicle (HbV), a type of artificial oxygen carrier, was infused in a hemorrhagic shock model, and the findings were compared with those of red blood cell (RBC) transfusion to evaluate the effects on blood pressure and renal function. In rats maintained in hemorrhagic shock for 30 min under general anesthesia, either irradiated stored RBCs from the same strain or HbVs were used for resuscitation. Blood pressure, serum creatinine concentration, and creatinine clearance 24 h after shock were measured. At 2 and 24 h after shock, the kidneys were removed, and the heme oxygenase-1 (HO-1) mRNA level was measured. A histopathology study was performed 24 h after shock. In both the RBC and HbV group, blood pressure recovered significantly immediately after fluid resuscitation, and blood pressure 24 h after shock did not differ significantly between the two groups. Serum creatinine concentration and creatinine clearance 24 h after shock did not differ significantly between the two groups. After 24 h, there was no significant difference in HO-1 mRNA between the groups. In the renal histopathology samples taken at 24 h after shock, there were no obvious differences between the two groups. In conclusion, HbV transfusion improved blood pressure in a manner equivalent to RBC transfusion when administered during hemorrhagic shock, and no renal dysfunction was apparent after 24 h.

We report a staghorn renal calculus case with squamous cell carcinoma of the renal pelvis producing granulocyte colony-stimulating factor. A 77-year-old woman was followed-up at our institution for 3 years for lower right ureter stone and right staghorn calculus. She was admitted to our hospital complaining of right flank pain and a discharging abscess in her lower back 2 months after a bicycle accident. Radiological evaluations lad to the diagnosis of a large right renal abscess. Although daily percutaneous drainage had previously been performed, her general condition did not improve. Diagnosing a renal abscess, we performed nephro-ureterectomy and retroperitoneal irrigation. Pathological examination revealed squamous cell carcinoma of the renal pelvis producing granulocyte colony-stimulating factor. Although three courses of cisplatin and fluorouracil (5FU) chemotherapy were administered, the patient had a remarkable degree of leukocytosis despite no obvious focus of infection, with aggravated local recurrence of the tumor. The patient died 6 months after surgery. A summary of our case and a review of the literature are presented.

Background and Objective: Anesthesiologists need to be familiar with perioperative changes in blood volume (BV); however, there is no standard method for repeated evaluation of BV over a short interval of time. We evaluated BV in the operation room using repeatable estimation methods. Method: Eighty-five ASA physical status I-II patients scheduled to undergo endoscopic urosurgery using irrigation fluid under general anesthesia at Nippon Medical School Hospital were included in this study. Irrigation with 3% sorbitol in water was commenced after establishment of general anesthesia and volumetric fluid balance, which was defined as control water balance (WB). Hematocrit (Hct), colloid osmotic pressure (COP), total protein (TP) and albumin (Alb) were repeatedly determined before and during anesthesia. BV was calculated using Allen’s formula and the changes in Hct, COP, TP and Alb. Main Outcome Measures: The main outcome was the accuracy of measuring changes in BV (△BV) calculated using the four serum markers. WB and the estimated △BV calculated from Hct, COP, TP and Alb (△BV-Hct, △BV-COP, △BV-TP, and △BV-Alb) were analysed using Pearson’s correlation coefficient test and Bland-Altman analysis. Results: Sixty-five patients were excluded. In the remaining 20 patients, there was a significant correlation between WB and △BV-COP (R2 = 0.72; P △BV-TP (R2 = 0.59; P △BV-Alb (R2 = 0.57; P △BV-Hct (R2 = 0.06). Conclusion: △BV-COP, △BV-TP and △BV-Alb had correlation with WB. However, since COP can be measured repeatedly with simplified instruments under selected clinical circumstances, while TP and Alb cannot. COP is the most useful marker to measure △BV during perioperative period. Hct does not allow precise estimation of △BV.

We experienced a case of interstitial lung disease (ILD) that occurred one year after the start of everolimus therapy for renal cell carcinoma. The pathological features included interstitial pneumonia with granuloma formation. Everolimus is known to cause ILD; however, its pathology is unclear. Granuloma-forming interstitial pneumonia associated with everolimus is uncommon, although it may be one of the pathological patterns associated with everolimus-induced ILD. This is a slow-onset case of everolimus-induced ILD in a patient with renal cell carcinoma. Physicians should thus be aware of the potential for the development of ILD at any time during the administration of everolimus therapy.

We reported the experience with a case of plasmacytoid variant of urothelial carcinoma of urinary bladder. A 75-year-old woman complained of gross hematuria. She was hospitalized to be diagnosed as the bladder tumor on abdominal CT. TUR-BT was performed and pathological finding was invasive urothelial carcinoma. But she refused radical cystectomy. 2 months later, she was hospitalized again with worsening hematuria. Simple cystectomy was performed. Histological examination revealed a plasmacytoid appearance of the infiltrating tumor cells. Immunohistochemical stains for lymphoid markers were negative. Those findings lead to the diagnosis of plasmacytoid variant of urothelial carcinoma. She died due to local recurrence for 1.5 months after simple cystectomy.

Background: We used transcatheter arterial infusion chemotherapy (TAI) for patients with T1G3 and greater than T2 bladder cancer, which was diagnosed after extensive and deep transurethral resection of bladder tumor (TUR-BT), and we investigated the utility of serum cytokeratin 19 fragment (CYFRA) as a predictive factor of the response to therapy. Material and Methods: From November 2001 to November 2010, 56 patients (46 males and 10 females) with pathologically confirmed T1 G3 or greater than T2 bladder cancer after TUR-BT underwent two courses of TAI of cisplatin, methotrexate and doxorubicin as neoadjuvant setting. Then, patients underwent evaluation TUR-BT. Thereafter, the bladder was preserved in patients with superficial or undetectable tumors on TUR-BT. Advanced cases and residual bladder tumor cases were treated with total cystectomy or systemic chemotherapy. CYFRA levels were measured before and after performing TAI. Results: With this therapy, the 5-year survival rate was 85.7% in pT1G3, 82.3% in pT2, and 66.6% in greater than pT3 cases. Bladder preservation with no recurrence was observed in 58.7% of the patients. Grade III adverse events included leucopenia (6/56 patients: 10.7%). Serum CYFRA levels significantly decreased with treatment (in 4/6 patients with elevated CYFRA levels). Conclusion: These results suggest that although total cystictomy is usually indicated for T1G3 bladder cancers, bladder preservation and control of micrometastases can be achieved by performing TAI after extensive and deep TUR-BT. Our results also suggest the utility of monitoring serum CYFRA to assess the response to therapy.

This report describes creation of a bone-anchored sling with the InVance™ system (American Medical Systems, Minnetonka, MN, USA) for the treatment of 2 patients with incontinence after radical prostatectomy. The InVance™ system uses a silicon-coated polyester sling positioned under the bulbar urethra via a perineal incision. The sling is attached to both ischiopubic rami by 3 titanium screws. Operative times were 157 minutes (patient 1) and 240 minutes (patient 2). Blood loss was 70 mL (patient 1) and 10 mL (patient 2). The patients used 7 and 5 absorbent pads/day, respectively, before surgery and 1 and 0 pads/day after surgery (this datum does not appear in the main text, although the absence of incontinence is mentioned). The only major adverse event encountered was mesh infection necessitating mesh removal in patient 2. This operation appears comparatively simple and useful.

To investigate whether the metabolic syndrome is a risk factor for lower urinary tract symptoms (LUTS), as defined by the International Prostate Symptom Score (IPSS).A total of 900 men underwent digital rectal examination of the prostate and completed an IPSS questionnaire. These men had visited our hospital for metabolic screening from April 2008 to March 2009. The IPSS includes scores for 3 questions on voiding symptoms, 3 on storage symptoms, and 1 on postmicturition symptoms. The relationships of the LUTS (determined from the IPSS subscores) with the metabolic syndrome diagnosed using the Japan Society for the Study of Obesity, 2005 National Cholesterol Education Program-Adult Treatment Panel III, and 2005 International Diabetes Federation criteria were examined. The severity of LUTS was compared among the younger, middle-age, and older men (50, 50-64, and ≥65 years old, respectively) with and without the metabolic syndrome.A diagnosis of the metabolic syndrome was made in 16.7%, 16.6%, and 11.7% of the men using the Japan Society for the Study of Obesity, 2005 National Cholesterol Education Program-Adult Treatment Panel III, and 2005 International Diabetes Federation criteria, respectively. Regardless of the presence of the metabolic syndrome, aging was significantly associated with an increased rate of moderate or severe LUTS, except for postmicturition symptoms. In the middle-age men, the metabolic syndrome had a significant negative correlation with storage symptoms (odds ratio 0.258-0.426). In the younger and older men, LUTS was observed equally in those with and without the metabolic syndrome.A relationship between age and LUTS was observed; however, the metabolic syndrome did not show a clear association with LUTS. Our results suggest that LUTS is associated with aging, regardless of the presence of the metabolic syndrome.

Rationale:Collecting duct carcinoma (CDC) is a rare type of nonclear renal cell carcinoma, often presenting at an advanced stage of the disease, and standard treatment guidelines have not been established.Patient concerns:A 73-year-old man was admitted to our hospital with complaints of feve

Objectives: To investigate the androgen response of hormone-dependent prostate cancer cells under hypoxia and to examine the effect of geldanamycin (GA), a heat shock protein 90 (Hsp90)-specific inhibitor, on the androgen response. Methods: LNCaP cells were cultured with or without GA under normoxic or hypoxic conditions. Cell viability was examined in response to dihydrotestosterone (DHT). Luciferase reporter gene assay was used to measure androgen response element (ARE)- and hypoxia response element (HRE)-mediated transcriptional activities. Western blot was used to analyze the protein levels of androgen receptor (AR), hypoxia-inducible factor-1α (HIF-1α) and Hsp90. Results: The DHT-dependent growth and ARE-mediated transcriptional activities of LNCaP cells were depressed under hypoxic conditions. However, these effects were recovered after incubation with GA. In contrast, hypoxia-induced HRE-mediated transcriptional activity, which was dose-dependently increased by DHT, was suppressed by GA. The expression of AR, HIF-1α and Hsp90 proteins were decreased under hypoxic conditions by adding GA. Conclusions: Geldanamycin increases the androgen response regardless of AR protein in hormone-dependent prostate cancer cells under hypoxic conditions.

142 Background: Low-dose-rate brachytherapy (BT) is the internal radiation therapy for non-metastatic prostate cancer by implanting radioactive isotope Iodine 125 into the prostate. The carcinogenetic effect of radiation for the treatment of cancer has been proven during the last decades. However, few studies have been reported about brachytherapy-induced secondary malignancies. In this study, we assessed the BT-induced secondary malignancies in our institution. Methods: We reviewed 487 patients treated with low-dose-rate BT from 2006 to 2016 in our hospital. We checked the occurrence of metachronous malignancies (MM) in all the patients and examined the features of MM including the number, organ sites, histology, period from BT to the occurrence, and analyzed whether the features meet the criteria of radiation-induced malignancies. We also examined the relationship between the BT-related radiation doses and the occurrence of MM. We adopted the criteria of radiation-induced cancer proposed by Sakai et al in 1981; different pathological feature from the organ of origin, the follow-up duration after radiation therapy (over 5 years), and whether the lesion is located in the irradiated field. Results: After a median follow-up period of 57 months (range 10-125 months), 23 MM occurred, which were bladder cancer in 4 cases (0.8%), esophageal in 2 (0.4%), gastric in 5 (1.0%), colon in 4 (0.8%), rectal in 3 (0.6%), pancreatic in 1 (0.2%), lung in 3 (0.6%), and brain in 1 (0.2%). Time from initial treatment to MM was 36 months (range 1-85 months). None of the cases had experienced biochemical recurrence. Average radiation dose to the urethra and the rectum including UD90, UD5, U200, R100, R150 showed no significant difference compared to the patients without occurrence of MM. According to the Sakai’s criteria, one bladder and one rectal cancer were judged as radiation-induced secondary malignancies (0.2%). Conclusions: The risk of secondary malignancies in patients undergoing BT was very low. Further studies with longer follow-up are required because it has been only about 10 years since low-dose-rate brachytherapy started in Japan.

487 Background: Lipid cell variant (LCV) of urothelial carcinoma (UC) which was first described by Mostofi et al in 1999 is a very rare variant of UC. Because it has only been documented in occasional case reports and a small series about this variant since then, clinicopathological characteristics of LCV are not yet clarified. In this study, we assessed the clinicopathological characteristics of LCV experienced in our hospital. Methods: The medical records of patients with LCV, who were treated in our hospital between September 2015 and September 2017, were retrospectively reviewed and analyzed. Results: In this period, of 301 patients undergoing TURBT and 42 patients undergoing nephroureterectomy, 13 patients including 10 patients with bladder cancer and 3 with pelvic ureter cancer, were found to be diagnosed as LCV of UC at our hospital. The median observation period of these patients was 6 months (IQR, 4-9 months). Among 10 bladder cancer patients who had confirmed this variant in transurethral resection of bladder tumor (TURBT) specimens, all cases had concurrent high-grade UC and the most cases had tumor features including pT2 or more local stages and lympho-vascular invasion (LVI) positive. Co-existence of micropapillary and/or plasmacytoid variant were seen in 5 patients. Lymph node metastases were observed in 3 patients, and this variant was histologically confirmed within the lymph node metastatic tissue in one case. No patient had distant metastasis. Among 3 pelvic ureter cancer patients who had undergone nephroureterectomy, all cases had concurrent high-grade UC and the most cases had tumor features including pT3 local stage and LVI positive. Micropapillary variant was coexisted in one patient. No patient had distant metastasis. 7 patients were no evidence of disease and 6 were alive with disease. The estimated median time from surgery to recurrence was not reached. The 6-months disease-free survival rate was 59%. Conclusions: LCV is seen in the patients who have high-grade UC, and tends to be accompanied with other aggressive variants including micropapillary and plasmacytoid. All patients with this variant had advanced stage cancer at presentation with high recurrence rates.

562 Background: The standard treatments have been established for metastatic germ cell tumors and the cure rates are quite improving. Cumulative experience by centralization is required for expertise in all aspects of care but it is quite difficult due to its rarity and the present medical situations in Japan. To resolve this problem, we established the nation-wide internet tumor board system for testicular cancer from 2012. Methods: To start with, 28 members from 14 institutions were registered in the internet mailing list (ML) for this tumor board, then the members who wanted to join this system were added to this ML. The tumor board was operated in semi-closed system and with no consultant fee. The member can present the case by e-mail at any time when he encounters the difficult case. Then the other members replied and commented their opinions or experiences against his questions by e-mail. All members could read his case-presentation and comments of consultants in e-mail. In this study, we summarized the initial 5-year experience and the discussed contents and the usage status were analyzed to assess the quality of this internet nation-wide reference system. Results: The number of members and discussed cases increased gradually. At the present, this ML consists with 179 members from 79 institutions all over Japan. We discussed 100 testicular cancer cases during 5 years. Discussed cases were categorized into 10 categories. 44% of the cases discussed in the ML were poor prognostic cases or extragonadal cases. In 63 cases, the consultants were replied within 24 hours when the case was presented in ML, and some comments were replied within at 5 days in all cases. The median number of comments was 6, and active discussions with 10 or more comments were performed in 26 cases (26%). Conclusions: The nation-wide internet tumor board system for testicular tumor was growing in Japan and useful to decide treatment strategy for difficult cases. It might be helpful for members in low volume centers to gain cumulative experience.

628 Background: LDA in solid RCC on CT is often interpreted as ‘central necrosis’ in routine clinical practice. However, the details of clinicopathological (CP) features of LDA of RCC on CT and their prognostic significance have not been shown. We retrospectively investigated LDA of RCC to clarify the CP features and prognostic significance. Methods: Of 428 surgically treated patients for RCC between January 2007 and March 2017 at Nippon Medical School hospital, we found 267 cases who had dynamic CT performed before operation. Among them, we selected and analyzed 199 consecutive cases whose tumor had low density area and whose cancer status resulted in no evidence of disease after surgery. We first examined pathological features of LDA. Then, we examined the correlation between pathological features of LDA and CP parameters and prognosis. The differences of values between the three groups were examined with the Kruskal-Wallis test. Recurrence free survival (RFS) was examined with the Kaplan-Meyer curves and the log-rank test. Results: The histology of LDA was divided into two groups: central necrosis (+) or (-: NN). Central necrosis (+) group was further divided into two subgroups: with neutrophilic infiltration (NI+) and without NI (NI-). This means that, in the end, there were three groups according to microscopic findings: group A (NI+, n = 20, 10%), B (NI-, n = 55, 28%), C (NN, n = 124, 62%). The pathological features of the NN group were composed of hyaline degeneration, hydropic degeneration, fibrosis, scars, and so on. The results of the comparison between CP parameters among the three groups were as follows: C-reactive protein, WBC, platelet, and alkaline phosphatase are statistically higher, and hemoglobin, triglyceride, and albumin were statistically lower in group A. CT value was statistically lower in group A and B. Median follow-up was 35months, and 3-year RFS (group A, B, C, p value) was (49.8%, 77.9%, 94.3%, p < 0.0001). Conclusions: In RCC patients only about one-third of LDA on CT was shown to be central necrosis. Necrosis with NI was clinically most closely associated with poor prognosis. Central necrosis may be predictive from lower CT values compared to non-necrotic tissues.

There are no guidelines regarding whether to perform either a radical transurethral resection of the bladder tumor (TUR-BT) or a total cystectomy after TUR biopsy for huge bladder cancer, and this decision is entrusted to each institution. Of 439 patients in whom TUR-BT was performed from 2005 through 2009, the weight of the total resected volume was > 50 g in 6 patients, and among these 6 patients the following variables were compared: operating time, weight of resected volume, transfusion volume, presence or absence of hydronephrosis, preoperative urinary cytology, serum cytokeratin 19 fragment (CYFRA) level, intraoperative bladder compliance, and histopathological findings. The median age, operating time, weight of resected volume, transfusion volume, and length of follow-up were 72 years, 300 minutes, 88 g, 202 mL, 16 months, respectively. The serum CYFRA level in patients with muscle-invasive cancer (11.8 ng/mL) was higher than that in patients with non-muscle-invasive cancer (5.06 ng/mL). All patients with non-muscle-invasive bladder cancer survived without recurrence. Although the mean length of follow-up was only 16 months (5-59 months), the 1 patient who was followed up for 59 months had no recurrence. In cases of muscle-invasive bladder cancer, all patients, except for a relatively recent patient, have died. In cases without muscle invasion, lymph node metastasis, distal metastasis, or preoperative renal dysfunction accompanied by hydronephrosis, with favorable bladder compliance, we believe that radical TUR-BT should be actively performed to preserve the bladder. A second TUR-BT should be performed in cases of non-muscle-invasive cancer without G3 components to treat the huge bladder cancer.

A 33-year-old woman was referred to us by the department of urology because of cyclic bladder pain during menstruation. Cystoscopy showed a 3.5-cm-diameter tumor in the bladder mucosa, and a biopsy showed chronic cystitis. Transvaginal ultrasound and pelvic magnetic resonance imaging revealed a left endometrial ovarian cyst. Although a biopsy did not prove bladder endometriosis, we diagnosed bladder endometriosis on the basis of the characteristic clinical findings. Laparoscopic partial cystectomy for bladder endometriosis and left ovarian endometrial cyst resection were performed. The bladder was closed in one layer using Z sutures with #3-0 polyglactin 910. Indigo carmine dye was then used to check for any leakage. The procedure lasted 4 hours, and the estimated blood loss was 10mL. There were no technique problems or complications. The Foley catheter was removed after 7 days. The symptoms had resolved by 4 weeks after surgery, and the patient was released to routine follow-up. The patient had complete resolution of bladder symptoms and cyclic pelvic pain and was delighted with the absence of pain and the cosmetic result.

The lower urinary tract symptoms in elderly men are composed of from voiding symptoms and storage symptoms. The representative disease with voiding symptoms is benign prostatic hyperplasia, and the representative syndrome with storage symptoms is overactive bladder and nocturia. Diagnosis by asking questions that use International Prostate Symptom Score and the overactive bladder symptom score is important. The first-line drugs for the treatment of the lower urinary tract symptoms are α1-blockers. Behavior therapy and anticholinergic drugs are also useful for treating storage symptoms.

We have demonstrated 340-nm-band high-output-power InAlGaN quantum well (QW) ultraviolet (UV) light-emitting diodes (LEDs) under room temperature (RT) continuous wave (CW) operation, which were deposited on sapphire (0001) substrates by low-pressure metal–organic chemical vapor deposition (LP-MOCVD). The high-output-power UV LEDs were achieved by introducing p-type InAlGaN layers in order to obtain a high hole concentration and by optimizing the band lineup to suppress electron overflow. The output power of a UV-LED with p-InAlGaN layers was about 4.7 times larger than that of an equivalent structure containing p-AlGaN. We obtained a significant increase in output power by controlling the barrier height of the electron-blocking layer (EBL) and the depth of the quantum wells. We also obtained a marked increase in UV output power by introducing a low-threading-dislocation-density (TDD) AlN buffer layer. The maximum output power and external quantum efficiency (EQE) of LEDs containing p-InAlGaN layers were 8.4 mW and 0.9%, respectively, at an emission wavelength of 346 nm under room temperature (RT) CW operation.

The safety of a new technique, designated "transcatheter arterial embolization (TAE) with aspiration via a balloon-occluded renal drainage vein" (TAE-ABOD), for the management of large renal cell carcinomas (RCCs). The subjects were 25 patients with RCC who underwent a total of 27 sessions of TAE-ABOD. This TAE-ABOD technique incorporates two procedures: balloon occlusion of renal drainage vein and infusion of absolute ethanol into the tumor-feeding arteries during aspiration of blood via a balloon catheter, thereby reducing leakage of absolute ethanol into the systemic circulation. Our primary endpoint was to establish a safe regimen for high-dose ethanol injection therapy, and our secondary endpoint was to assess global survival of the patients. The administered dose of ethanol ranged from 0.2 to 0.5 ml/kg [median: 0.34 (SD: 0.10) ml/kg], increased in a stepwise manner. The systemic ethanol concentration was measurable in 14 patients, and was less than 0.1 mg/ml in 12 and from 0.1 to less than 0.2 mg/ml in two. There were no major complications such as renal failure or renal abscess. TAE-ABOD can safely deliver a high dose of absolute ethanol for the treatment of large RCCs.

High output power 340 nm-band InAlGaN-based multi-quantum-well (MQW) ultraviolet (UV) light-emitting diodes (LEDs) were achieved by using p-type InAlGaN layers. The output power of a UV-LED with p-type InAlGaN layers was approximately 4.7 times larger than that achieved with p-type AlGaN layers. We obtained an output power of 8.4mW from a 346 nm InAlGaN-QW LED by optimizing the band line-up to suppress electron overflow and by reducing the threading dislocation density (TDD) of the AlN/AlGaN template.

Nonpolar a-plane GaN epilayers were grown by metalorganic vapour phase epitaxy on r-plane sapphire substrates using three different buffer layer structures. The investigated structures consisted of GaN grown on: (A) AlN nucleation layer; (B) AlN plus Al0.25Ga0.75N intermediate layer; (C) AlN, Al0.25Ga0.75N, and GaN/Al0.25Ga0.75N superlattice. The samples were characterized by X-ray diffraction, transmission electron microscopy, and atomic force microscopy. Structure (B) exhibited much lower overall structural defect densities than structure (A), with narrower X-ray rocking curves by a factor of 1.5-2. Compared to structure (B), structure (C) showed a factor of 2 lower density of screw dislocations in TEM although the densities of other types of defects were not significantly reduced. Type (B) and (C) structures also exhibited smoother surface morphologies than Type (A). (© 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

The patient was a 37-year-old woman who had suffered from repeated pyelonephritis. Computed tomography (CT) of the abdomen revealed a 1.9 cm retroperitoneal mass with compression of the right ureter and hydronephrosis. The patient visited our medical center and admitted. The patient underwent a simple total excision of the mass and end-to-end ureteral anastomosis. The tumor involved right ovarian vein and right ureter. Histopathological diagnosis was leiomyosarcoma of the ovarian vein. At 12 months after operation, local recurrence of surroundings tissue of the right ureter and gallbladder, and inferior vena cava invasion is found. Thus, the patient underwent a right nephroureterectomy with partly resection of the inferior vena cava and en block excision of the gallbladder. While CT revealed no recurrence three months after the operation, adjuvant postoperative combination chemotherapy with gemcitabine and docetaxel was administered. Nine cases of this leiomyosarcoma arising from ovarian vein have been reported in the literature. Leiomyosarcoma arising from ovarian vein with hydronephrosis is a second example.

To investigate associations between dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) expression and survival in T1 high-grade or T2 bladder cancer patients treated with neoadjuvant chemotherapy. The cohort under investigation comprised 44 patients who underwent neoadjuvant chemotherapy for pT1 high-grade or pT2N0M0 bladder cancer at our institution between 2002 and 2011. Immunohistochemical analysis was used to determine expression of DYRK2 in bladder cancer specimens obtained by transurethral resection before chemotherapy. Relationships between DYRK2 expression and both response to chemotherapy and survival in these patients were analyzed. DYRK2 expression was positive in 21 of 44 patients (47.7 %) and negative in 23 patients (52.3 %). In total, 20 of 21 DYRK2-positive cases showed complete response to neoadjuvant chemotherapy, whereas 11 of 23 DYRK2-negative cases did not show complete response. Sensitivity and specificity were 62.5 % and 91.7 %, respectively (P = 0.0018). In addition, disease-specific survival rate was significantly higher for DYRK2-positive patients than for DYRK2-negative patients (P = 0.017). In multivariate analysis, DYRK2 expression level was identified as an independent prognostic factor for disease-specific survival (P = 0.029). We also showed that DYRK2 mRNA expression was significantly higher in DYRK2-positive samples by immunohistochemistry than DYRK2-negative samples (P = 0.040). DYRK2 expression level may predict the efficacy of neoadjuvant chemotherapy for T1 high-grade and T2 bladder cancer.

INTRODUCTION AND OBJECTIVES: The natural history of prostatic lesions identified on multiparametric MRI (mpMRI) is unknown. We aimed to describe changes observed over time on serial mpMRI, and to determine especially how these influenced management of men on active surveillance (AS). METHODS: Between January 2008 and October 2014, 754 men underwent mpMRI, of whom 65 had 2 studies. Imaging findings and corresponding clinico-pathologic parameters were compared and related to the discontinuation of AS. RESULTS: Serial mpMRIs were performed for AS monitoring in 42 men and for suspicion of prostate cancer in 23 men. Collectively, there were 93 lesions on 1st mpMRI and 143 on 2nd mpMRI for analysis. The median time between scans was 19.7 months (IQR 13.529.5). New lesions were seen in 34 of 65 (52.3%) patients. The Median (IQR) number of lesions seen per patient increased from 1 (1-2) to 2 (13). Lesion size increased in 29.4% (mean 3.0 mm/yr) and decreased in 18.5% (mean -2.1mm/yr ). The ADC value decreased in 47.9 % of lesions (>300 unit decrease in 15%) between scans and increased in a further 25 %. Three of 47 (6%) lesions moved from ADC>600 to ADC

To assess whether our ureteroscopic real-time navigation system has the possibility to reduce radiation exposure and improve performance of ureteroscopic maneuvers in surgeons of various ages and experience levels.Our novel ureteroscopic navigation system used a magnetic tracking device to detect the position of the ureteroscope and display it on a three-dimensional image. We recruited 31 urologists from five institutions to perform two tasks. Task 1 consisted of finding three internal markings on the phantom calices. Task 2 consisted of identifying all calices by ureteroscopy. In both tasks, participants performed with simulated fluoroscopy first, followed by our navigation system. Accuracy rates (AR) for identification, required time (T) for completing the task, migration length (ML), and time exposed to simulated fluoroscopy were recorded.The AR, T, and ML for both tasks were significantly better with the navigation system than without it (Task 1 with simulated fluoroscopy vs with navigation: AR 87.1 % vs 98.9%, P=0.003; T 355 s vs 191 s, P0.0001; ML 4627 mm vs 2701 mm, P0.0001. Task 2: AR 88.2% vs 96.7%, P=0.011; T 394 s vs 333 s, P=0.027; ML 5966 mm vs 5299 mm, P=0.0006). In both tasks, the participants used the simulated fluoroscopy about 20% of the total task time.Our navigation system, while still under development, could help surgeons of all levels to achieve better performances for ureteroscopic maneuvers compared with using fluoroscopic guidance. It also has the potential to reduce radiation exposure during fluoroscopy.

Introduction: Characteristics of prostatic fluid (PF), which can be obtained in large amounts during screening transrectal ultrasound just before prostate biopsy to detect prostate cancer, were investigated. These characteristics include the amount of PF obtained and the number of leukocytes in PF, which would be useful for planning cell-biological or immunological studies of leukocytes in PF and for increasing the understanding of prostatitis in elderly men. Patients and Methods: The volume of PF and the number of leukocytes in PF were measured in 50 patients suspected of having prostate cancer because of elevated levels of serum prostate-specific antigen (PSA). Correlations of the volume of PF, the number of leukocytes per milliliter, the total leukocyte number with age and prostate volume and correlation of PSA levels with the number of leukocytes per milliliter and total leukocyte number were also investigated. Results: The average patient age was 67.2 years, and PF specimens were obtained from 43 of the 50 patients (86%). The mean ± SD of PF volume, number of leukocytes in PF, and total leukocyte number were 347.65 ± 305.76 μl, 4.84 ± 6.07 × 106 /ml, and 1.47 ± 2.10 × 106, respectively. A correlation was observed only between the total leukocyte number and the volume of the transitional zone (P=0.039). Conclusions: These data provide information for investigators to plan cell-biological or immunological studies of leukocytes in PF and for understanding prostatitis in elderly men.

We report high efficiency blue organic electroluminescent (OEL) devices having a metal-doped electron injection layer at the cathode interface. The typical device structure is an indium-tin oxide (IIO)/arylamine derivative (α-NPD)/blue emitting distyrylarylene derivative/metal-doped organic electron injection layer/Al. The device efficiency is dependent on the work function of the dopant metals and the host organic materials composing the metal-doped layer. A device having Cs-doped bathophenanthroline (Bphen) layer as the cathode interface layer exhibited a high luminous efficiency of 9 lm/W and an external quantum efficiency of 6.5% at luminance of 300 cd/m 2 , which are the highest values reported for blue organic EL devices

Purpose: Isolated pelvic perfusion (IPP) therapy exposes target tissues to high doses of anticancer drugs with low systemic concentrations, but the major drawback is drug leakage into the systemic circulation, which often thwarts the increased drug concentration. In this study, the efficacy of altering the in-out flow rate during IPP in order to decrease the leakage was assessed in adult pigs. Methods: The abdominal aorta and the infrarenal vena cava were occluded with two balloon catheters, blood in the extracorporeal circuit was circulated with twin rotary pumps, and the IPP was performed with platinum. Three sets of in-out flow rates were used, and the degree of drug leakage into the systemic circulation was evaluated. The volume of blood withdrawn was equal to the volume returned (300 ml/min; group A), 5% higher (group B), or 10% higher (group C). The platinum concentrations in the pelvic circulation, systemic circulation, and urine were measured and compared. Results: The average and maximum plasma platinum concentrations in the pelvic circulation did not significantly differ among the three groups. The plasma platinum concentrations in the systemic venous circulation of the three groups significantly (P

The hypoxia-inducible factors 1alpha (HIF-1alpha) and 2alpha (HIF-2alpha) have extensive structural homology and have been identified as transcription factors that mediate hypoxia-inducible gene expression through hypoxia-responsive element (HRE). They play critical roles not only in normal development, but also in tumor progression. Endothelial cells (EC) express both HIF-1alpha and -2alpha. In this study, we examined the subcellular localization of HIF-1alpha and -2alpha in bovine arterial EC (BAEC) by immunoblotting and immunocytostaining analysis and found that even under normoxic conditions, as with its heterodimeric partner ARNT, HIF-2alpha was stable, and was localized in the nucleus of BAEC differently than HIF-1alpha. HIF-2alpha might be regulated by a different mechanism than HIF-1alpha and might mediate the expression of some EC-specific genes under normoxic conditions. We further found that cardiovascular helix-loop-helix factor (CHF) 2, which had been identified as an ARNT-interacting protein, was expressed in BAEC and suppressed HRE-dependent gene expression both under normoxia and hypoxia. CHF2 might be one of the key regulators of HIF-2alpha-mediated gene expression in normoxic EC.

Five- and ten-year survival rates in patients who had transurethral resection for pT2aN0M0 muscle invasive transitional cell carcinoma of the bladder was studied with emphasis on the effect of adjuvant transarterial infusions of anticancer agents (TAI). A total of 17 patients out of 290 patients with bladder cancer who had initial treatment in our department between January 1991 and May 2001 were found to be pT2aN0M0 and were included in the present study. Fifteen patients received intravesical instillations of BCG after transurethral resection of the bladder tumor and 8 patients received TAI which was given two weeks after bacillus Calmette-Guerin therapy, with the exception of 1 patient. Five- and ten-year overall survival rates were 76.0% and 52.1%, respectively, and both five- and ten-year cancer-specific survival rates were 76.0% with an average follow up of 71 months. Significant prognostic factor associated with survival rates was only the infiltration pattern of the tumor cells between the alpha and beta group and gamma group (P = 0.0420) in cancer-specific survival rates. The data support conservative management of transurethral resection followed by intravesical instillation of BCG and TAI in patients with pT2a bladder cancer.

Attenuation of the renal toxicity of cis-diamminedichloroplatinum (CDDP) is important in the use of this effective but cytotoxic anticancer agent. We have previously shown that the renal toxicity of CDDP can be efficiently reduced by the induction of metallothionein (MT) by preadministration of bismuth compounds in mice. Bismuth subnitrate (BSN) is used as an antigastric ulcer agent and as an antidiarrheic agent, and is suitable for inducing MT in the kidney in cancer patients. However, due to the low absorption rate of Bi from the gastrointestinal tract, the efficacy of BSN in inducing renal MT is low. In the present study, we examined the effects of citrate as a vehicle for oral administration of BSN on the tissue distribution of Bi and induction of MT in the kidneys and tumors in mice inoculated with Meth-A fibrosarcoma. Renal levels of MT and Bi were markedly increased in the mice given BSN dissolved in citrate solution compared with those given BSN suspended in saline. On the other hand, the use of citrate increased Bi accumulation in the tumor only slightly and did not increase tumor MT levels. Administration of BSN with citrate efficiently depressed the renal toxicity of CDDP, but did not affect its antitumor activity. Since both BSN and citrate are used clinically as pharmaceuticals, the combination regimen of BSN and citrate may be readily applicable as a countermeasure against the adverse side effects of CDDP without affecting its antitumor activity.

Purpose: We investigated whether urine survivin an inhibitor of the apoptosis protein is useful for diagnosing bladder tumor. Method: We measured urine survivin levels in 40 patients with bladder tumors and 9 healthy volunteers. Results: The average urine survivin levels in the 40 patients and 9 healthy controls were not significantly different(3.802±8.669 and 1.127±1.529 respectively(p=0.3646) ) . However significantly high urine survivin levels were observed in 3 of the 40 patients but not in healthy volunteers. Urine Cyfra 21‑1 was not elevated(1.3 ng ml )in one patient with a significantly elevated urine survivin level(33.54 ng ml ) while in two patients with elevated Cyfra(320 ng ml and 240 ng ml ) the urine survivin level was not detectable. Conclusion: With improvements in the sensitivity of our Elisa system for urine survivin and combined use of urine Cyfra 21‑1 it is possible that urine survivin wil lb e au seful tumor marker in detecting both new‑onset and recurrent bladder tumors. (J Nippon Med Sch 2004; 71: 379―383)

The X-FEM proposed by Belytschko et al. uses interpolation functions based on the concept of partition of unity and considers discontinuity of displacement fields near a free surface and a crack independently of the finite element mesh. This paper describes the application of X-FEM to stress analyses of composite laminates. The interpolation functions of plate and solid finite elements used in three-dimensional analysis are extended to perform static and eigenvalue analyses for natural frequency and buckling load of composite laminates with an open hole and an interlaminar delamination. It was shown that the fairly good agreement between X-FEM and the conventional FEM were obtained. X-FEM can model the discontinuity at free surfaces much easier than conventional FEM. Using such advantages can help us to perform adequate considerations for damage evaluation of the composite materials.

The metal binding protein metallothionein (MT) confers drug resistance when MT is induced in tumor tissues. Cisplatin is known to induce MT synthesis in tumor tissues, which may lead to drug resistance. We examined whether a difference in the administration schedule of cisplatin affect the efficiency of MT induction.Balb/c nude mice were inoculated with NMB-1 human bladder tumor tissues and injected with cisplatin (total dose of 64 micromol/kg) in a single injection or fractioned daily injections. Tumor MT concentration was determined 24 hours after the last injection of cisplatin by mercury binding assay. The effect of pretreatment with ZnCl2 on antitumor activity of cisplatin was examined in NMB-1 bearing mice.Tumor MT levels increased significantly with the increase in the number of cisplatin injections. Pretreatment of NMB-1 bearing mice with ZnCl2 (200 micromol/kg x 2) caused the same level of MT induction (1.6-fold) as that of fractioned injections of cisplatin (4 x 16 micromol/kg). Pretreatment of NMB-1 bearing mice with ZnCl2 (200 micromol/kg x 2) depressed cisplatin antitumor activity by about 50%.The induction of MT to a moderate extent (1.6-fold) in NMB-1 tumor inoculated in mice conferred cisplatin resistance. This level of MT induction can be achieved by fractioned daily injections of cisplatin but not by a single injection. Therefore, it is preferable to administer cisplatin as a single injection rather than as fractioned injections to achieve effective antitumor activity with minimum MT induction.

Background. We carried out this study to clarify whether the operative methods of laparoscopic prostatectomy established in France could become standard therapy. The purpose was to evaluate the technical feasibility, oncological efficacy, and intraoperative and postoperative morbidity of laparoscopic prostatectomy performed by a general urologist. Methods. Between June 2000 and August 2002, 30 patients with clinically localized prostate cancer underwent laparoscopic radical prostatectomy performed as previously reported by Guillonneau and colleagues. Oncological data were assessed by pathological examination and by postoperative prostate-specific antigen (PSA) levels. All prostatectomy specimens were processed according to the Stanford protocol. Prostate features, including tumor weight; Gleason score; and the tumor status of the capsule, seminal vesicles, and surgical margins were studied. Results. Complete laparoscopic removal of the prostate and seminal vesicles was achieved in all 30 patients. Operating time averaged 325.5 min (range, 165 to 880 min). The transfusion rate for the patients in the series was 50%, using own-blood transfusion (800–1200 ml). No patient required an allogenic blood transfusion. Only 2 of the 30 patients had a positive surgical margin that involved the urethra. There were three complications: bladder injury, rectal injury, and ileus associated with a drainage tube. No vascular, nervous system, or urethral complications were found. Conclusion. These preliminary results demonstrated that radical prostatectomy can be performed laparoscopically by general urologists. Laparoscopy offered better luminosity and magnification than conventional procedures, permitting precise dissection. Thus, laparoscopic prostatectomy could be a standard operation for patients with clinically organ-confirmed prostate cancer.

Functional inactivation of the von Hippel-Lindau (VHL) tumor suppressor protein is the cause of familial VHL disease and sporadic kidney cancer. The VHL gene product (pVHL) is a component of an E3 ubiquitin ligase complex that targets the hypoxia-inducible factor (HIF) 1 and 2 alpha subunits for polyubiquitylation. This process is dependent on the hydroxylation of conserved proline residues on the alpha subunits of HIF-1/2 in the presence of oxygen. In our effort to identify orphan HIF-like proteins in the data base that are potential targets of the pVHL complex, we report multiple splice variants of the human HIF-3 alpha locus as follows: hHIF-3 alpha 1, hHIF-3 alpha 2 (also referred to as hIPAS; human inhibitory PAS domain protein), hHIF-3 alpha 3, hHIF-3 alpha 4, hHIF-3 alpha 5, and hHIF-3 alpha 6. We demonstrate that the common oxygen-dependent degradation domain of hHIF-3 alpha 1-3 splice variants is targeted for ubiquitylation by the pVHL complex in vitro and in vivo. This activity is enhanced in the presence of prolyl hydroxylase and is dependent on a proline residue at position 490. Furthermore, the ubiquitin conjugation occurs on lysine residues at position 465 and 568 within the oxygen-dependent degradation domain. These results demonstrate additional targets of the pVHL complex and suggest a growing complexity in the regulation of hypoxia-inducible genes by the HIF family of transcription factors.

The mechanism of cellular cadmium (Cd) uptake has been poorly understood. Recently, we developed Cd-resistant cell lines from metallothionein null mouse cells and showed that the Cd resistance of these cells was conferred primarily by a reduced Cd accumulation. Surprisingly, the uptake rate of manganese (Mn) was also markedly reduced in Cd-resistant cells. Subsequent studies on the kinetics of Cd and Mn uptake by Cd-resistant and parental cells revealed that the Mn transport system with high affinity for Mn is used for cellular Cd uptake, and that this pathway is suppressed in Cd-resistant metallothionein null cells. This is the first indication that the transport system for Mn is used for Cd uptake in mammalian cells. Divalent metal transporter 1 (DMT1) is the only known mammalian transporter involved in the uptake of both Cd and Mn. However, the high-affinity Mn/Cd transport system we found seems to be distinct from DMT1 because of the difference in optimal pH and substrate specificity. On the other hand, various types of Mn transporters have been shown to play an important role in cellular Cd uptake in non-mammalian species such as yeast, plants and bacteria, suggesting the existence of Mn transporters other than DMT1 in mammals.

Cyclooxygenase (COX), which catalyzes the synthesis of prostaglandins from arachidonic acid, has two isoforms; COX-1 and COX-2. A large body of evidence exists to suggest that COX-2 is important in gastrointestinal cancer. In order to determine whether COX-2 is expressed in transitional cell carcinoma (TCC) of the human bladder as well as in gastrointestinal cancer, we investigated COX-2 expression in human TCC by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and immunohistochemical analysis, and we found that normal bladder epithelium did not express COX-2 and that COX-2 was markedly up-regulated in human bladder TCC. In nontumor tissues, COX-2 immunostaining signals were observed only in lymphoid follicles. Furthermore, the intensity and extent of COX-2 immunostaining in the bladder cancer tissues were scored and the relationship to tumor grade and stage was investigated. The levels of COX-2 expression were correlated with the tumor grade; from grades 1 to 3, there was a stepwise increase in the COX-2 immunostaining score. These findings suggested that an increase in COX-2 expression may be associated with bladder carcinogenesis as well as gastrointestinal carcinogenesis, and that it may be useful as a biomarker in bladder cancer.

Background To investigate associations between dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) expression and survival in T1 high-grade or T2 bladder cancer patients treated with neoadjuvant chemotherapy. Methods The cohort under investigation comprised 44 patients who underwent neoadjuvant chemotherapy for pT1 high-grade or pT2N0M0 bladder cancer at our institution between 2002 and 2011. Immunohistochemical analysis was used to determine expression of DYRK2 in bladder cancer specimens obtained by transurethral resection before chemotherapy. Relationships between DYRK2 expression and both response to chemotherapy and survival in these patients were analyzed. Results DYRK2 expression was positive in 21 of 44 patients (47.7 %) and negative in 23 patients (52.3 %). In total, 20 of 21 DYRK2-positive cases showed complete response to neoadjuvant chemotherapy, whereas 11 of 23 DYRK2-negative cases did not show complete response. Sensitivity and specificity were 62.5 % and 91.7 %, respectively (P = 0.0018). In addition, disease-specific survival rate was significantly higher for DYRK2-positive patients than for DYRK2-negative patients (P = 0.017). In multivariate analysis, DYRK2 expression level was identified as an independent prognostic factor for disease-specific survival (P = 0.029). We also showed that DYRK2 mRNA expression was significantly higher in DYRK2-positive samples by immunohistochemistry than DYRK2-negative samples (P = 0.040). Conclusions DYRK2 expression level may predict the efficacy of neoadjuvant chemotherapy for T1 high-grade and T2 bladder cancer.

Vesicovaginal fistulas (VVFs) caused after radiation are difficult to repair and require interposition of non-irradiated, well-vascularized tissue between urinary bladder and vagina. A 48-year-old female suffered cervical cancer and underwent radical hysterectomy followed by radiation therapy which caused VVF. The initial surgical repair performed 3 months after development of VVF, was unsuccessful because of the absence of peritoneum or omentum to interpose between urinary bladder and vagina probably due to history of cesarean section and radical hysterectomy. The second surgical repair was performed 15 months after the first surgery utilizing a rectus abdominus myofascial (RAM) interposition flap. Fifteen months after the second operation, she remains free from incontinence. This case suggests that RAM is useful even for postradiation VVF.

To investigate whether the insertion of a thermoexpandable metallic prostate stent (Memokath) facilitates the removal of Foley catheters in elderly patients ineligible for urethral obstruction surgery because of the potential complications involved in long-term catheter management.A total of 37 male patients (mean age 79.8 ± 6.2 years) ineligible for surgery under general anesthesia because of advanced age, the presence of post-cerebrovascular disorders or anticoagulant therapy use and who subsequently had a Memokath stent inserted between June 2007 and November 2009 were enrolled in the present study. Patients with spinal injury were excluded. We compared the correlation between prostatic urethral length and total prostate volume (TPV). We also evaluated the postoperative postvoid residual (PVR) and presence of pyuria, and reviewed postoperative complications and unassisted urination ability.We found a positive correlation between prostatic urethral length and TPV. After the insertion of the Memokath stent, the catheters were removed from all patients who could urinate unassisted. The PVR was50 mL in 76.4% patients, and there was a 52% improvement in pyuria after insertion of the Memokath stent. The mean postoperative follow-up duration was 33.2 ± 16.7 months. A total of 21 patients (56.7%) were able to urinate unassisted after receiving the Memokath stent. Unassisted urination was difficult in patients with poor performance status. No serious complications were observed after insertion of the Memokath stent.The Memokath stent was safe and useful for elderly patients with urethral obstruction and good performance status requiring long-term management with urethral Foley catheters.

(Pinteraction 1⁄4 0.609). Among individuals with GSTM1 null and present genotypes, the corresponding ORs were 2.91 (95% CI, 0.44-19.09) and 4.21 (95% CI, 1.26-14.14), respectively (Pinteraction 1⁄4 0.712). CONCLUSIONS: Our findings support the hypothesis that genetic factors play a role in bladder cancer etiology. Whether these correspond to low-penetrance cancer-predisposing polymorphisms acting together and/or interacting with environmental factors warrants further research.