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The purpose of this work is to understand quantitative processes which underlie the initiation of stress corrosion cracking (SCC) of cold-worked, thermally treated Alloy 690 after long-term exposures in high-temperature water. Long-term stress corrosion cracking initiation tests up to 34,484 h have been performed on cold-worked, thermally treated Alloy 690 under static load conditions using 0.5T compact tension specimens with a shallow depth of the precrack (0.1 mm to approximately 0.3 mm) and blunt notch compact tension type specimens. These specimens were exposed in the primary coolant environments of pressurized water reactors under static load conditions both at 320°C and 360°C. Three important patterns were observed. First, intergranular cracking observed from the shallow precracks after 21,838 h at 320°C and 20,653 h at 360°C, respectively, in 20% cold-worked Alloy TT690 in primary water. Second, clear evidence of cavities were identified ahead of the SCC-tip after the tests both at 360°C and 320°C....

This paper describes a novel multi-scale study of stress corrosion cracking in cold-worked 304 type stainless steels, which are widely used in pressurized water reactors and boiling water reactors. The influence of cold work and Cr concentration on the stress corrosion cracking behaviour of the steel has been examined. A methodology has been developed in order to characterize the same crack tip region with nanoscale secondary ion mass spectroscopy, electron back-scattering diffraction and transmission electron microscopy. This has offered a unique insight into the chemistry and microstructure, showing that the right combination of techniques can provide much of the information needed to understand the processes involved in crack propagation. A model for crack propagation based on brittle fracture and localized oxidation and shearing near the crack tip has been proposed. © 2009 Acta Materialia Inc.

The rates of SCC growth were measured under simulated PWR primary water conditions (500 ppm B + 2 ppm Li + 30 cm3/kg-H2O-STP DH2) using cold worked 316SS and 304SS. The direct current potential drop method was applied to measure the crack growth rates for 53 specimens. Dependence of the major engineering factors, such as yield strength, temperature and stress intensity was systematically examined. The rates of crack growth were proportional to the 2.9 power of yield strength, and directly proportional to the apparent yield strength. The estimated apparent activation energy was 84 kJ/mol. No significant differences in the SCC growth rates and behaviors were identified between 316SS and 304SS. Based on the measured results, an empirical equation for crack growth rate was proposed for engineering applications. Although there were deviations, 92.8% of the measured crack growth rates did not exceed twice the value calculated by the empirical equation.

The effect of several vitamin K homologs on plasma vitamin K concentration was determined to assess their potential as a vitamin K supplement for adult horses. Sixteen Thoroughbred horses consisting of 8 mares and 8 geldings, aged 8.4 ± 3.6 yr and weighing 520.8 ± 36.1 kg, were allocated to 4 groups (n = 4). Each group was given phylloquinone, menaquinone-4, or menadione at 58 µmol/d, or no vitamin K supplement for 7 d. Plasma samples were collected before feeding, and 2, 4, and 8 h after feeding on d 7, and plasma concentrations of phylloquinone and menaquinone-4 were determined. Plasma phylloquinone concentration was greater in the phylloquinone group than in the other groups (P < 0.001). The phylloquinone concentration quadratically increased (P < 0.001) after feeding in the phylloquinone group but no changes in the plasma phylloquinone concentration were observed after feeding in the other groups. Plasma menaquinone-4 concentration was greater (P < 0.001) in the menadione group than the other groups, including the menaquinone-4 group. Menaquinone-4 concentration did not change (P = 0.192) after feeding in each group. Menaquinone-4 has been considered the most potent vitamin K homolog for bone metabolism; therefore, the present experiment indicates that menadione is a good source of vitamin K for bone health in horses because it is the only vitamin K homolog that increased the plasma concentrations of menaquinone-4.

The growth rate of stress corrosion cracking (SCC) was measured for nonsensitized and sensitized, cold-worked Type 316 (UNS S31600, CW316) and Type 304 (UNS S30400, CW304) in hydrogenated ...

The rate of stress corrosion cracking (SCC) was measured for nonsensitized, cold-worked Type 316 (UNS S31600) and Type 304 (UNS S30400) in both hydrogenated pressurized water reactor (PWR)...

The intergranular stress corrosion cracking (IGSCC) growth behavior of austenitic stainless steels (SS) in hydrogenated high-temperature water were studied using compact tension specimens ...

The influence of material factors on the intergranular stress corrosion cracking (IGSCC) susceptibility of austenitic stainless steels under hydrogenated high-temperature water were studie...

The distributions of the local internal stress near the grain boundaries in 20 % cold-rolled SUS316 stainless steel were measured under the external tensile stress of 0 and 300 MPa using the Energy-dispersive X-ray Diffraction Microscopy (EXDM) technique at BL28B2 of SPring-8. The local internal stresses near the grain boundaries were successfully evaluated. The results indicated that the evidence that the internal stress concentration was occurred at the grain boundaries under the external tensile stress.

Cold-worked 304 stainless steels (SS) are known to be susceptible to stress corrosion cracking (SCC). This study employs atom-probe tomography (APT) for local chemical analysis of the oxides formed. Autoclave experiments on a set of samples with/without cold-work prior to oxidation, and with/without stress applied during oxidation, were carried out under simulated pressurised water reactor (PWR) primary conditions. APT and analytical transmission electron microscopy (ATEM) were combined to investigate chemical and structural implications of surface and grain boundary oxidation in 304 SS. Focussed ion beam (FIB) milling was used to prepare specimens containing the same grain boundary for every analysis technique. Grain boundary and deformation band oxidation were observed in all but the unstressed and non-cold worked sample. Cavities were found ahead of the Cr-rich oxide in some of the samples. APT data suggests the presence of hydrogen in Nickel-rich regions.

A laparoscopic radical nephrectomy with an attendant lymphadenectomy was performed on two patients with stage 1 renal cell carcinoma. Using a laparoscopic procedure through five trocar ports, kidneys bearing early stage renal cell carcinoma could be freed in the abdominal cavity, just as in open surgery. Many patients with early stage renal cell carcinoma, usually found incidentally, could benefit from this less invasive procedure.

The effect of several vitamin K homologs on plasma vitamin K concentration was determined to assess their potential as a vitamin K supplement for adult horses. Sixteen Thoroughbred horses consisting of 8 mares and 8 geldings, aged 8.4 ± 3.6 yr and weighing 520.8 ± 36.1 kg, were allocated to 4 groups (n = 4). Each group was given phylloquinone, menaquinone-4, or menadione at 58 µmol/d, or no vitamin K supplement for 7 d. Plasma samples were collected before feeding, and 2, 4, and 8 h after feeding on d 7, and plasma concentrations of phylloquinone and menaquinone-4 were determined. Plasma phylloquinone concentration was greater in the phylloquinone group than in the other groups (P0.001). The phylloquinone concentration quadratically increased (P0.001) after feeding in the phylloquinone group but no changes in the plasma phylloquinone concentration were observed after feeding in the other groups. Plasma menaquinone-4 concentration was greater (P0.001) in the menadione group than the other groups, including the menaquinone-4 group. Menaquinone-4 concentration did not change (P = 0.192) after feeding in each group. Menaquinone-4 has been considered the most potent vitamin K homolog for bone metabolism; therefore, the present experiment indicates that menadione is a good source of vitamin K for bone health in horses because it is the only vitamin K homolog that increased the plasma concentrations of menaquinone-4.

HIFU has been recognized as a minimally invasive treatment option for localized prostate cancer. The purpose of the study was to assess with a long‐term outcome of HIFU for prostate cancer. From January 1999, a total of 657 patients who had HIFU with at least 2 year follow‐up were treated with four different types of Sonablate® (Focus Surgery, Indianapolis, USA) devices. Thirty‐three patients were treated with Sonablate® 200 (S200) from 1999 to 2001, 406 patients with Sonablate® 500 (S500) from 2001 to 2005, 200 patients with Sonablate® 500 version 4 (V4) from 2005–2008 and 19 patients with Sonablate® 500 TCM (TCM) from 2007. Biochemical disease‐free survival rate (bDFS) in all patients was 59% in 8 years. bDFS in 8 years in patients with S200 and S500 groups were 55% and 56%, and bDFS in 4 and 2 years in patients with V4 and TCM group were 72% and 84%, respectively. bDFS in low, intermediate, and high risk groups were 75%, 54%, and 43% in S200/S500 and 93%, 72%, and 58% in V4/TCM group. Negative prostate...

To investigate the use of minimally invasive high‐intensity focused ultrasound (HIFU) as a salvage therapy in men with localized prostate cancer recurrence following external beam radiotherapy (EBRT), brachytherapy or proton therapy. A review of 20 cases treated using the Sonablate® 500 HIFU device, between August 28, 2002 and September 1, 2009, was carried out. All men had presumed organ‐confined, histologically confirmed recurrent prostate adenocarcinoma following radiation therapy. All men with presumed, organ‐confined, recurrent disease following EBRT in 8 patients, brachytherapy in 7 patients or proton therapy in 5 patients treated with salvage HIFU were included. The patients were followed for a mean (range) of 16.0 (3–80) months. Biochemical disease‐free survival (bDFS) rates in patients with low‐intermediate and high risk groups were 86% and 50%, respectively. Side‐effects included urethral stricture in 2 of the 16 patients (13%), urinary tract infection or dysuria syndrome in eight (26%), and urinary incontinence in one (6%). Recto‐urethral fistula occurred in one patient (6%). Transrectal HIFU is an effective treatment for recurrence after radiotherapy especially in patients with low‐ and intermediate risk groups.

Nuclear influences on mitochondrial genome organization were analysed in four cytoplasmic male sterile sunflower lines harbouring the Petiolaris sterile cytoplasm. This cytoplasm originates from the interspecific cross of Helianthus petiolaris and Helianthus annuus and was studied in different nuclear backgrounds. The mitochondrial genome organization in these different lines was compared by Southern blot analysis using five different mitochondrial genes as probes to identify potential alterations due to nuclear effects. The mitochondrial rearrangements of the investigated sterile lines are restricted to the atp A area and are independent of the nuclear backgrounds. Restoration of fertility by nuclear genes does not affect the mitochondrial DNA arrangement. The applicability of the atp A gene as a molecular marker for verifying the quality of hybrid seed production in sunflower is discussed.

The nucleotide divergence of chloroplast DNAs around the hot spot region related to length mutation in Triticum (wheat) and Aegilops was analyzed. DNA sequences (ca. 4.5 kbp) of three chloroplast genome types of wheat complex were compared with one another and with the corresponding region of other grasses. The sequences region contained rbcL and psaI, two open reading frames, and a pseudogene, rpl23' (pseudogene for ribosomal protein L23) disrupted by AT-rich intergic spacer regions. The evolution of these genes in the closely related wheat complex is characterized by nonbiased nucleotide substitutions in terms of being synonymous/nonsynonymous, having A-T pressure transitions over transversions, and frequent changes at the third codon position, in contrast with the gene evolution among more distant plant groups where biased nucleotide substitutions have frequently occurred. The sequences of these genes had diverged almost in proportion to taxonomic distance. The sequence of the pseudogene rpl23' changed approximately two times faster than that of the coding region. Sequence comparison between the pseudogene and its protein-coding counterpart revealed different degrees of nucleotide homology in wheat, rice and maize, suggesting that the transposition timing of the pseudogene differed and/or that different rates of gene conversion operated on the pseudogene in the cpDNA of the three plant groups in Gramineae. The intergenic spacer regions diverged approximately ten times faster than the genes. The divergence of wheat from barley, and that from rice are estimated based on the nucleotide similarity to be 1.5, 10 and 40 million years, respectively.

A Cameca NanoSIMS 50 has been used to map trace elements in stainless steels from nuclear reactors. The results prove that it is an ideal technique to map elements in small concentrations such as boron, sulphur or phosphorous which remain inaccessible to conventional microanalysis techniques. Especially remarkable is the ability to map boron, revealing segregation to grain boundaries or to carbides in sensitized samples. © 2008 Elsevier B.V. All rights reserved.

High-resolution analysis using a Cameca NanoSIMS 50 has been used to map the oxide chemistry in intergranular cracks in stainless steels. The technique has proven ideal for this type of sample, as it is able to discern between the different oxide layers and clarify the role of minor segregants such as boron and sulphur. Results are compared with analysis of the same sample by scanning auger microscopy and its interpretation discussed. The short time required to prepare and examine multiple regions present the NanoSIMS as an optimum tool for corrosion characterization. © 2007 Elsevier B.V. All rights reserved.

Many related species and strains of common wheat were compared by matching differences among their mitochondrial genomes with their "parent" nuclear genomes. We examined three species of Aegilops, section Sitopsis (Ae. bicornis, Ae. sharonensis, and Ae. speltoides), emmer wheat (Triticum dicoccoides, T. dicoccum, and T. durum), common wheat (T. spelta, T. aestivum, and T. compaction), and timopheevi wheat (T. araraticum, T. timopheevi, and T. zhukovskyi). A single source of the cytoplasm was used in all the species, except Ae. speltoides (two sources), T. araraticum (two), and T. aestivum (three). Following restriction endonuclease analyses, the mitochondrial genomes were found to comprise seven types, and a dendrogram showing their genetic relatedness was constructed, based upon the percentage of common restriction fragments. MtDNAs from T. dicoccum, T. durum, T. aestivum, and T. compactum yielded identical restriction fragment patterns; these differed from T. dicoccoides and T. spelta mtDNAs in only 2.3% of their fragments. The fragment patterns of T. timopheevi and T. zhukovskyi were identical, and these differed from T. araraticum mtDNA by only one fragment. In both the emmer-dinkel and timopheevi groups, mitochondrial genome differentiation is evident, suggesting a diphyletic origin of each group. MtDNAs from four accessions of the Sitopsis species of Aegilops differ greatly from one another, but those of Ae. bicornis, Ae. sharonensis, and Ae. searsii, belonging to the same subsection Emarginata, are relatively similar. MtDNAs of timopheevi species are identical, or nearly so, to those of Ae. speltoides accession (09), suggesting that the latter was the cytoplasm donor to the former, polyploid group. The origin of this polyploid group seems to be rather recent in that the diploid and polyploid species possess nearly identical mitochondrial genomes. We cannot determine, with precision, the cytoplasm donor to the emmer-dinkel group. However, our results do suggest that mitochondrial DNAs show larger evolutionary divergence than do the ctDNAs from these same strains.

In gynodioecious plant populations, sex determination often involves both cytoplasmic male-sterility (CMS) genes and specific nuclear genes that restore male function. How gynodioecy is maintained under the joint dynamics of CMS and restorer genes remains controversial. Although many theoretical models deal with interactions between CMS genes and restorer genes with sexual phenotypes and predict changes in their frequencies, it is difficult to observe the frequencies because no molecular markers have been established for either CMS or restorer genes in well-studied gynodioecious plants. This is the first report of the frequency of a CMS gene determined using a molecular marker in natural populations of a gynodioecious plant. Using a set of CMS gene-specific polymerase chain reaction primers, we compared female and CMS gene frequencies in 18 natural populations of Raphanus sativus. Female frequency was relatively low, ranging from 0 to 0.21. In contrast, the CMS gene frequency was highly variable among populations, ranging from 0 to 1. Estimated restorer gene frequency seemed less variable than observed CMS gene frequency, probably due to higher gene flow than in the CMS gene. Genetic drift may play a role in maintaining high variability of the CMS gene, although other possibilities are not excluded.

A 72-year-old man had undergone surgical castration for metastatic prostate cancer (stage D2, the PSA value was 4,300 ng/ml) in September, 1997. He was well clinically for 16 months with undetected level of PSA. However, he presented with general malaise and gross hematuria in May, 1999. After admission to our hospital his condition rapidly deteriorated and he died one week later with respiratory failure. Autopsy revealed extensive involvement of the prostate and bladder by solid tumor with multiple metastases in lungs, liver, spleen, kidneys and bone. Histological examination revealed pure small cell carcinoma of the prostate.

A 62-year-old man was admitted with a chief complaint of general malaise. Computed tomography showed a large mass adjacent to the parenchyma of the left kidney. The mass was 17 x 13 x 12 cm in size. Preoperative diagnosis was left renal cell carcinoma and left radical nephrectomy was performed. Histopathologically, the tumor was diagnosed as malignant fibrous histiocytoma (MFH), and the tumor was considered to have arisen from the renal capsule. There has been no recurrence for 7 months postoperatively. We review 40 cases of MFH arising from the kidney or the renal capsule in the literature.

Five cases of urachal carcinoma experienced in our hospital during the past 20 years are reported. Surgical resection is considered as the first treatment option of this disease, and other therapies to be less beneficial. Complete surgical extirpation and detection of recurrence in the early stage are considered to be important since local recurrence occurs frequently. We enforced the bladder preserving operation for 4 patients with urachal carcinoma except for 1 case with peritonitis carcinomatosa in the initial diagnosis, and multiple surgical treatment was performed again for 2 patients with recurrence. The bladder was preserved with no evidence of malignancy in three patients for 24, 19 and 5 years, respectively. In the initial management of urachal carcinoma, we believe that bladder-preserving surgery should be considered in selected cases though close follow-up is demanded. Herein, we also report the immunohistochemical study of paraffin-embedded specimens using anti-CEA, CA19-9, CA125 and p53 monoclonal antibodies. The positive reaction was observed in 100% (5/5) for CEA, 80% (4/5) for CA19-9, and 20% (1/5) for CA125. These results suggest that CEA may be a useful marker in the diagnosis of this neoplasm and early detection of its recurrence. Nuclear accumulation of p53 was observed in 80% (4/5), but it did not correlate with the disease progression.

To review the contemporary management of benign prostatic hyperplasia (BPH) in Japan during 1990s, we analyzed several nationwide health statistics by the Ministry of Health and Welfare of Japan. The cross-sectional surveys revealed that the estimated total number of patients receiving treatment increased from 202,000 in 1987, to 335,000 and 590,000, respectively, in 1995 and 1998. Approximately 73-80% of patients were men aged 65 years or over and 94-98% 55 years or older. Urologists treated two thirds of the BPH patients. The incidence of prostatectomies remained relatively stable at 50,000/year (3.0-3.8 prostatectomies/1,000 men aged 55 or over). The average hospital stay in 1996 was 24.7 days. The total cost of BPH therapy nearly doubled between 1988 and 1998. The ratio of outpatient to inpatient costs ranged from 1.5 to 2.2 and 60% of the outpatient cost was spent for medical therapy. The total value of the market for medical therapy increased from 30-40 billion yen in 1989 to more than 80 billion yen in 1998. The application of alpha-blockers increased from 243,000 men (70% of all patients) in 1995 to 452,000 (77%) in 1998, whereas the number of patients taking antiandrogens, plant extracts and antispasmodic agents/Ca antagonists (for pollakisuria), respectively, remained relatively stable at 60,000-70,000, 180,000 and 300,000. Because Japan is a rapidly aging society and men aged 55 or older are expected to increase from 15 million in 1995 to 21 million in 2010, cost-effective treatment guidelines for the Japanese BPH patients are needed.

Epididymal sperm aspiration technique combined with assisted reproductive technology (ART) including intracytoplasmic sperm injection (ICSI) has provided new frontiers for the treatment of unreconstructable obstructive azoospermia, including congenital bilateral absence of the vas deferens and failed surgical intervention. Epididymal sperm is obtained by several procedures, including microsurgical epididymal sperm aspiration (MESA), mini-MESA (Modified MESA), macroscopic epididymal sperm aspiration (MaESA) and percutaneous epididymal sperm aspiration (PESA). Since 1991 in our department, epididymal sperm aspiration combined with ART was performed by MESA (26 cases, 41 times) and PESA (3 cases, 4 times). Motile sperm retrieval using MESA and PESA was obtained in 34 out of 36 times (94.4%) and 2 out of 4 times (50%), respectively. MESA-ICSI resulted in a 47.3% 2PN (metaphase II) fertilization rate per eggs and a 28.8% pregnancy rate per transfer. With advancement of ICSI technique in which frozen sperm can be used, elective sperm retrieval can be planned at our convenience. PESA is a convenient, inexpensive and effective outpatient clinic procedure for retrieving sperm assisted with ICSI. In summary, infertile couples need to be given realistic options regarding treatment outcome. The fertility potential and age of the female partner need to be considered when addressing male treatment options.

Recent applications of laparoscopy to urologic surgery have demonstrated the efficacy, safety, and shorter convalescence times with these techniques. Laparoscopy still is the most accurate diagnostic tool for impalpable testes and allows surgeons to select the proper treatment. Because of the need for general anesthesia, laparoscopic varicocelectomy is not considered less invasive than subinguinal low ligation under local anesthesia. However, a future trend toward day surgery might favor laparoscopy, which requires a smaller skin incision and thus enables young men to return to work earlier. Laparoscopic adrenalectomy has been established as a standard operative technique because it offers many advantages in comparison with conventional open surgery. Laparoscopic nephrectomy is also a minimally invasive operation, although the most appropriate method for kidney retrieval has not been determined, and currently in Japan insurance reimbursements are limited to benign disease. Laparoscopic nephrectomy for renal cell carcinoma and upper urinary tract transitional cell carcinoma is very promising, although there is debate on laparoscopic cancer surgery. Furthermore, the recent great success with laparoscopic radical prostatectomy in France is stimulating Japanese investigators. In the 21st century, laparoscopy will be standard for many surgical procedures in urology.

Few attempts have been made at the molecular detection of urothelial cancer cells in the blood or lymph nodes mainly because of an absence of good candidate molecular or genetic changes specific to urothelial cancer or urothelium. In 1990, however, genes that encode urothelium-specific transmembrane proteins, uroplakins (UPs), were cloned. We have established a method of detecting circulating cancer cells in peripheral blood of patients with transitional cell carcinoma by nested reverse transcription-PCR assay for UP II. UP II mRNA-positive cells were detected in 3 (10.3%) of 29 patients with superficial cancers (pTa-1N0M0), 4 (28.6%) of 14 patients with muscularly invasive cancers (pT2-4N0M0), 2 (40.0%) of 5 loco-regional node-positive patients (pN1-2M0), and 6 (75.0%) of 8 patients with distant metastases. Positive rates, therefore, increased with tumor extension (P = 0.0033, Kruskal-Wallis test). Furthermore, sequential blood sampling was performed in three patients with metastases during and after systemic chemotherapy, and UP-II-positive cells were found to have disappeared in two patients who responded well to the systemic chemotherapy. These results suggest that our nested reverse transcription-PCR assay for UP II is highly specific and might be used as a tumor marker for molecular staging of urothelial cancers, although the sensitivity is not so optimal.

To assess the efficacy and toxicity of chemotherapy for advanced germ cell tumors, 115 patients with testicular and extragonadal germ cell tumors were reviewed. Five-year survival rates of 19 seminoma patients and 96 non-seminoma patients were 84% and 68%, respectively. According to the analysis using three sets of prognostic criteria, Indiana University Classification, International Germ Cell Consensus Classification and K Classification, the 5-year survival rate of poor-prognosis patients was 42-45%. BEP regimen (bleomycin, etoposide and cisplatin) salvaged with VIP (etoposide, ifosfamide and cisplatin) would be the standard therapy for advanced germ cell tumors since high-dose chemotherapy had no advantage on survival over the standard-dose regimen. Early serious toxicities were observed in 18 patients (15.7%), including pulmonary fibrosis, respiratory distress, and sepsis. Poor performance status and prior radiotherapy were risk factors for fatal adverse effects. In terms of late toxicites, out of 76 patients in complete remission for at least one year after cessation of chemotherapy, 31 had numbness of extremities and 29 had tinnitus. Serial semen analyses of 38 patients showed continuous azoospermia or severe oligozoospermia in 22. These data indicated that less toxic therapy was required for good-risk patients to improve the quality of life, while more intensive therapy for poor-risk patients to be cured. Several prognostic criteria should be utilized to properly distinguish good- from poor-risk patients, and decide how to treat each patient.

The efficacy and toxicity of a single cycle of high-dose chemotherapy with peripheral blood stem cell autotransplantation (PBSCT) in patients with poor-risk testicular germ cell tumors (GCT) enrolled in the Japan Blood Cell Transplantation Study Group was investigated. Previously untreated poor-risk testicular GCT patients were treated with BEP therapy (cisplatin, etoposide and bleomycin) with or without high-dose chemotherapy (carboplatin, etoposide and ifosphamide) followed by PBSCT. Patients were qualified for a change to high-dose chemotherapy if elevated serum tumor markers (human chorionic gonadotropin-beta, alpha-fetoprotein and lactate dehydrogenase) was observed after 3 cycles of BEP therapy. Eighteen patients were treated with BEP therapy alone and 16 with BEP and high-dose chemotherapy. At the completion of high-dose chemotherapy, all tumor markers had returned to normal in 6 patients. Among them, 1 had only teratoma found at resection and 5 had carcinoma resected. Nine patients who had persistent elevation of any tumor marker were treated with high-dose chemotherapy or another anticancer drug. Thirteen are alive (81%) and 9 (56%) are continuously disease-free at a median follow up of 11 months. The median time from PBSCT to a granulocyte count500/microL was 9.5 days and to a platelet count50,000/microL was 13 days.

Extended abstract of a paper presented at Microscopy and Microanalysis 2009 in Richmond, Virginia, USA, July 26 – July 30, 2009

We report a case of bilateral breast metastases from prostatic carcinoma. A 49-year-old man with stage D2 prostate cancer, who had been treated by chemoendocrine therapy and radiotherapy for 2 years, complained of bilateral enlarged breasts. Oral administration of diethylstilbestrol diphosphate was started 2 months before the onset of this symptom. A firm mass that was not tender was palpable beneath the skin without fixation on each side. A needle biopsy of the masses showed poorly differentiated adenocarcinoma with positive immunohistopathological staining for prostate-specific antigen. The masses were diagnosed as metastatic adenocarcinoma of prostate gland origin. The patient died 3 months after the diagnosis of breast metastases. Autopsy revealed diffuse lymphogenous metastatic disease. Metastatic prostatic carcinoma to the breast is uncommon. Breast metastases in this patient might be associated with diffuse lymphogenous metastases as well as increased local blood and lymphatic supply caused by extrinsic estrogens.

We report a case of transitional cell carcinoma in a patient with chronic renal failure receiving hemodialysis for 22 years. A 55-year-old man was admitted to our hospital. Under diagnosis of invasive bladder cancer and left renal pelvic tumor, removal of the whole urinary tract, e.g., bilateral nephroureterectomy and total cystourethrectomy was performed. Transitional cell carcinoma was found in bilateral renal pelvis, left ureter, bladder and prostate in the resected specimen. Thirteen months after the operation, multiple lung metastases and pathologic bone fracture of the 4th lumber vertebra were found. Chemotherapy (3 courses of modified CISCA, consisting of cisplatin, adriamycin and cyclophosphamide) was performed, but the died of systemic metastases of cancer and bleeding due to perforation of multiple gastric ulcers.

Recent clinical trials have implied the cytotoxic and antiproliferative effects of combining 5-fluorouracil and interferon-alpha in the treatment of metastatic renal cell cancer. We therefore conducted an open multicenter trial to test the efficacy of such a combination on this cancer.Human lymphoblastoid interferon (3 MIU per patient) was administered subcutaneously three times weekly for 12 weeks, while 5-fluorouracil was administered (600 mg/m2/day) as a continuous infusion for the first 5 days, followed by an intravenous bolus infusion of 600 mg/m2 once a week from the 3rd week until the 12th week.Of the 63 patients entered into the trial, 55 were eligible and evaluable for systemic toxicities, and 53 were evaluable for their response. All patients had undergone a prior nephrectomy, and their European Cooperative Oncology Group (ECOG) performance status ranged from 0 to 3 (median 0). Three complete and eight partial responses were induced, with an overall response rate of 20.0%. The median time to progression and the median survival time were 11 and 33 months, respectively. World Health Organization grade 3 toxicities were observed in 8 patients; however, no grade 4 toxicities or toxicity-related deaths were noted.Combination therapy of interferon-alpha plus 5-fluorouracil at the above-described dosage and schedule produced no better responses than interferon monotherapies. Prolongation of survival could be attributable to the fair performance status of the patients. This regimen has limited value for the treatment of patients with advanced renal cell cancer.

Recent molecular genetic studies have suggested that multifocal urothelial cancers are derived from an identical progenitor cell. However, the clonal origin of multifocal urothelial cancers of a low-grade superficial type has not been fully defined. Using microsatellite markers, we examined genetic alterations at 20 loci on eight chromosomal arms (2q, 4p, 4q, 8p, 9p, 9q, 11p, and 17p) in 87 metachronous and/or synchronous multifocal urothelial cancers, which included 84 low-grade superficial papillary tumors from 29 patients. Judging from the patterns of loss of heterozygosity, microsatellite shifts, and the subchromosomal partial deletion, multifocal tumors in at least 20 (80%) of the 25 evaluable patients were considered to be derived from a single progenitor cell, although the possibility remained that multifocal tumors in a small subset of patients might develop from distinct progenitor cells due to field cancerization. In 13 of the 20 patients, a chronological genetic analysis was available: genetic heterogeneity was detected in 3 (23%) patients, and an apparent accumulated pattern of genetic alterations was detected in only 1 (8%) patient. In the 20 patients with multifocal tumors of an identical clonal origin, discordant microsatellite alterations were observed, with significantly lower frequencies on chromosome 9 compared to those on the other chromosomes tested. The results indicate that most multifocal low-grade superficial urothelial cancers are genetically stable despite their incidence of frequent recurrence, and genetic divergence occurs in a subset of patients. This heterotopic spread and genetic divergence may occur long before the clinical manifestation of multiplicity from a single transformed cell. These data support the previous view that heterotopic spread of transformed progenitor cells and genetic divergence occur after chromosome 9 alterations in most of low-grade superficial urothelial cancers.

Nephrogenic adenoma is a rare, benign tumor of the urinary tract. The origin of this tumor is supposed to be a metaplastic transformation of urothelium in response to stimulation such as recurrent urinary tract infections or surgical trauma. We experienced three cases of nephrogenic adenoma originating in the bladder. The first patient was a 29-year-old man with right vesicoureteral reflux (VUR). When Teflon injection for VUR was performed, a papillary tumor was found on the right wall of the bladder. Transurethral resection of the bladder tumor (TUR-Bt) was performed. The second patient was a 72-year-old woman who was suffering from chronic cystitis. Although she was treated with antibiotics for one year, the symptoms were not improved. Cystoscopy showed multiple papillary tumors at the retrotrigonum of the bladder and TUR-Bt was performed. The third patient was a 75-year-old man who had a history of the left pelvic and bilateral ureteral tumors. Left radical nephroureterectomy and right radical ureterectomy with an ileal graft replacement was performed. Three years later, cystoscopy demonstrated a papillary tumor at the retrotrigonum, which was resected transurethrally. Our cases are the 20th to 22nd cases of the nephrogenic adenoma of the bladder reported in the Japanese literature.

Recently the combined therapy with interferon-alpha (IFN-alpha) and cimetidine has been reported to be effective against advanced renal cell carcinoma (RCC). IFN-alpha and cimetidine have an antitumor effect partly due to enhancement of cytotoxic activity of lymphocytes against cancer cells. We examined the expression of major histocompatibility complex (MHC) antigens and adhesion molecules on 4 fresh RCC cells and 5 RCC cultured cell lines, which have an important role in recognition and killing of cytotoxic lymphocytes against cancer cells. The effect of treatment with IFN-alpha and/or cimetidine on the expression of MHC antigens and adhesion molecules on RCC cells was also investigated. MHC class I and leukocyte function-associated antigen-3 (LFA-3) were expressed on all RCC cells, but not MHC class II. Intercellular adhesion molecule-1 (ICAM-1) and B7 were expressed on 6 and 5 of 8 RCC cells, respectively. IFN-alpha significantly augmented the expression of MHC class I in 6 of 9 RCC cells, ICAM-1 in 1 and LFA-3 in 2 of 8 RCC cells. However, IFN-alpha did not affect the expression of MHC class II and B7. On the other hand, cimetidine enhanced the expression of LFA-3 in 2 of 8 RCC cells, but not MHC antigens, ICAM-1 or B7. The combination of IFN-alpha and cimetidine did not show a synergistic enhancing effect on the expression of MHC antigens, ICAM-1, LFA-3 or B7. These results suggest that IFN-alpha augments the sensitivity of RCC cells to lysis by cytotoxic lymphocytes partly due to the enhancement of expression of MHC class I, ICAM-1 and LFA-3 on RCC cells, and that cimetidine also augments the susceptibility of RCC cells to lymphocytes by the enhanced expression of LFA-3 on RCC cells.

A 45-year-old man was referred to our department for further examination of the renal complicated cyst which was found incidentally by ultrasonography. Another complicated cyst in the left kidney was detected by subsequent dynamic CT and ultrasonography, which suggested bilateral cystic renal cell carcinoma. Bilateral partial nephrectomy was performed. Intraoperative ultrasonography was useful for diagnosis of multilocular cystic renal cell carcinoma (MCRCC). It disclosed multiple septa of the right renal complicated cyst which were not revealed by any preoperative examinations. It was also a useful adjunct to partial nephrectomy. It helped to identify the extent of deep intra-parenchymal lesions. The final diagnosis was bilateral synchronous multilocular cystic renal cell carcinoma. This is the second case of bilateral synchronous multilocular cystic renal cell carcinoma reported in Japan. We reviewed the clinical characteristics of 59 cases of MCRCC in the Japanese literature including the present case.

Background Telomeres are specific structures located at the ends of chromosomes that help maintain chromosome stability. In most tissues, telomeres become shorter as cells divide, a phenomenon thought to be associated with limitations on normal cell proliferation. Almost all types of cancer cells, including bladder cancer cells, express the enzyme telomerase, which can maintain or extend telomere length. Purpose We examined telomerase activity in tumor specimens from a cohort of patients with bladder cancer and determined whether telomerase could be detected in exfoliated cancer cells present in urine from these patients. Methods Spontaneously voided urine specimens and bladder-washing fluids (obtained by propelling normal saline into the bladder through a catheter and then withdrawing the liquid contents) were taken from 45 patients before they underwent surgery. Telomerase activity was examined by means of the TRAP (telomeric repeat amplification protocol) assay on extracts of tumor samples from 42 patients and extracts of exfoliated cells in urine and bladder-washing fluid from 42 and 43 patients, respectively. Standard cytologic examination (Pap staining) of urine specimens was also used to detect exfoliated cancer cells. Results Telomerase activity was found in 41 (98%; 95% confidence interval [CI] = 87%-100%) of the 42 tumor samples examined. In contrast, it was not detected in normal bladder tissue from two autopsied individuals who were free of bladder cancer and five of six individuals who had bladder cancer. Telomerase was detected in exfoliated cells in 23 (55%; 95% CI = 39%-70%) of the 42 spontaneously voided urine specimens and in 36 (84%; 95% CI = 69%-93%) of the 43 bladder-washing fluids examined. Considering voided urine specimens and bladder-washing fluids together, telomerase was detected in exfoliated cells from 40 (89%; 95% CI = 76%-96%) of the 45 patients. Telomerase activity was not detected in bladder-washing fluids from 12 cancer-free individuals. Cancer cells were detected by means of standard cytologic examination in the urine of 19 (42%; 95% CI = 28%-58%) of the 45 patients. Urine cytologic examination detected cancer cells in one (8%; 95% CI = 0%-38%) of 12 patients with grade 1 tumors and in 13 (46%; 95% CI = 28%-66%) of 28 patients with grade 2 tumors. In contrast, telomerase activity was detected in exfoliated cells (in voided urine or bladder-washing fluids) from nine (75%; 95% CI = 43%-95%) of 12 patients with grade 1 tumors and from 27 (96%; 95% CI = 82%-100%) of 28 patients with grade 2 tumors. Conclusion and implication Telomerase activity can be detected in exfoliated cells in urine from patients with bladder cancer, and measurement of this activity appears to be more sensitive in detecting the presence of cancer than standard urine cytologic examination. These findings suggest that measuring telomerase activity in exfoliated cells would be useful in the diagnosis and follow-up of patients with bladder cancer, a possibility that warrants further study.

A patient with a primary malignant lymphoma surrounding the female urethra is reported. Despite the good response of the primary tumor to radiotherapy, the patient died shortly after diagnosis due to disseminated disease. We reviewed 16 cases of this rare entity reported previously.

Between 1988 and 1996, 23 male patients with bladder cancer underwent bladder substitution after cystectomy, using either the hemi-Kock, Hautmann, and Reddy procedures. The mean postoperative follow-up period was 36 months, with a range of 3 to 85 months. There were no perioperative deaths, and early postoperative complications occurred in 7 patients (30%); transient urine leak from the pouch in 4, wound infection in 3 and pyelonephritis in 2 patients. Twenty-two of the 23 patients (96%) were continent during the day, while 7 (30%) had nocturnal incontinence. All 3 patients with the Reddy procedure had nocturnal incontinence. Complete continence was preserved in 70% of the patients. Dysuria was seen in 4 patients, including retention in 1 patient. Late complications included urethral stricture in 3, wound hernia in 2, metabolic acidosis in 1, stone in the pouch in 1, and gallbladder stone in 1 patient. However, reoperation was necessary in 1 patient for internal urethrotomy and 1 patient for removal of a stone in the neobladder. Mild degree of hydronephrosis and unilateral reflux were seen in 3 patients each, and followed up conservatively. No urethral recurrence has occurred and only 1 patient died of cancer. The need for reoperation was very low and the high reservoir capacity resulted in continence from the beginning in most patients. We considered the neobladder useful as an alternative form of urinary diversion in selected cases.

A variety of malignancies have been linked to major histocompatibility complex genes, including the DRB1 alleles. The association of certain DRB1 antigens with renal cell carcinoma (RCC) has been both claimed and disclaimed. To determine whether HLA-DRB1 genotypes are associated with RCC, we used the modified PCR-RFLP method for the high-resolution HLA-DRB1 genotyping of 96 Japanese RCC patients. There were no significantly frequent HLA-DRB1 alleles, whereas the DRB1*0101 and *0405 alleles had significantly lower frequencies [P = 0.004, relative risk (RR) = 0.2 and P = 0.002, RR = 0.4) in the RCC patients than in the healthy Japanese controls (n = 1216). Moreover, patients with the HLA-DRB1 *0101 or *0405 allele tended to be in earlier stages and to have less aggressive tumors than patients with neither of these alleles. The corresponding serotyping subclassification, however, showed a significantly lower frequency only for DRB1-DR1 (P = 0.01, RR = 0.3). High-resolution genotyping is essential because the polymorphism of the peptide-binding domain of major histocompatibility complex class II molecules is more precisely determined by genotypes than serotypes. In addition, inherent technical difficulties and potential typing errors render serotyping inefficient. Our data suggest that HLA-DRB1*0101 and *0405 are protective alleles for both RCC development and tumor progression.

A rare case of exophytic hepatic hemangioma preoperatively diagnosed as a non-functioning adrenal tumor is reported. A 62-year-old man was admitted for treatment of primary hyper-parathyroidism and an incidental adrenal tumor. A 4.0 x 2.5 cm heterogeneous tumor located between the liver and the right kidney was detected by abdominal ultrasonography, computed tomography and magnetic resonance imaging. Color doppler images revealed no apparent blood flow. Since the tumor seemed to have originated from the liver under laparoscopy, an open partial hepatectomy was performed. Histopathological examination revealed cavernous hemangioma of the liver. When diagnosing non-functioning right adrenal tumor, it may be necessary to carefully rule out an exophytic liver tumor.

The Mainz pouch with appendix-umbilical stoma is a very stable method for continent, self-catheterizable urinary reservoir in the presence of a healthy appendix. If the appendix is too short or an unexpected stenosis is seen at its distal portion, the elongation of the conduit using a part of the cecum and the implantation of the conduit to the pouch by the Mitrofanoff method can be a good alternative procedure. We herein report our experience in a 53-year-old male with high grade, invasive bladder tumor, who underwent cystourethrectomy and appendix Mainz pouch operation using the above technique.

A case of primary localized amyloidosis of the urinary bladder is reported. The patient was a 46-year-old female who suffered from macrohematuria and consulted our department. A yellowish non-papillary tumor at the retrotrigone of the bladder was observed on cystoscopy. Histological diagnosis was amyloidosis of the bladder. Since there was no evidence of disease in other organs, this patient was diagnosed with primary localized amyloidosis of the bladder and transurethral resection was performed. The clinical course was uneventful and she has been well without recurrence for 6 months postoperatively. This case was cured by transurethral resection, but close follow-up of the patients is necessary because of the recurrence.