A Case of Urachal Carcinoma of the Abdominal Wall in a Kidney Transplant Recipient.

Urachal carcinoma is an extremely rare malignant tumor arising from the urachus in the fetus. We report a patient who developed urachal carcinoma 18 years after kidney transplantation. A 59-year-old man was admitted because of abdominal pain and massive ascites. He had undergone kidney transplantation 18 years earlier and had end-stage renal disease requiring dialysis. Abdominal CT showed massive ascites and an abdominal wall cystic mass separated from the peritoneal cavity. Hemodialysis was started, and paralytic ileus was diagnosed and treated. His ileus symptoms improved temporarily, but he died of myocardial infarction. An autopsy was performed, which revealed cystadenocarcinoma in the abdominal wall mass, leading to a diagnosis of urachal carcinoma.

[A Case of Hydrocephalus Due to Brain Metastasis from Renal Cell Carcinoma Successfully Treated with Axitinib].

We report a case of hydrocephalus due to brain metastasis from renal cell carcinoma treated with axitinib. A 65-year-old man had undergone right radical nephrectomy for renal cell carcinoma in 2010. The pathological diagnosis indicated clear cell carcinoma G3, pT1a. After adjuvant treatment with interferon-α, computed tomography, in 2011, revealed multiple lung metastases. He was administered sorafenib. Because of progressive lung metastases, sunitinib was administered. The lung metastases were progressive and bone scan revealed multiple bone metastases. The patient was administered axitinib 10 mg/day in February 2014. Brain metastases were found in both the lateral ventricles in the same month and were controlled using axitinib. The patient, however, experienced adverse events such as diarrhea and hand foot syndrome, and the axitinib dosage was titrated. Cognitive function declined rapidly in August 2015. Brain magnetic resonance imaging revealed hydrocephalus due to brain metastasis from renal cell carcinoma. Axitinib was administered again. Cognitive function improved within approximately 10 days. Furthermore, hydrocephalus improved, and the patient was discharged on the 21st day.

Incremental Expression of 14-3-3 Protein Beta/Alpha in Urine Correlates with Advanced Stage and Poor Survival in Patients with Clear Cell Renal Cell Carcinoma.

We investigated the urinary levels of 14-3-3 protein beta/alpha to evaluate their diagnostic significance with regard to clear cell renal cell carcinoma (ccRCC) and angiomyolipoma (AML). Urine samples from 91 patients with ccRCC, 16 patients with AML and 24 healthy volunteers were assessed. We used an enzyme-linked immunosorbent assay (ELISA) to quantify 14-3-3 protein beta/alpha levels in urine. Values were higher in patients with ccRCC than in those with AML and in healthy volunteers. High levels were associated with pathologic stage, lymph node status, distant metastasis and poor survival. Urinary levels of 14-3-3 protein beta/alpha were significantly increased in patients with small-sized carcinoma, irrespective of being less than 4.0 cm and 2.0 cm, compared with levels in patients with AML. This study is the first to report that increased expression of 14-3- 3 protein beta/alpha in urine is associated with advanced stage and poor survival in patients with ccRCC. In addition, urinary 14-3-3 protein beta/alpha may differentiate AML from RCC, even when small sized. These results suggest that examination of urinary 14-3-3 protein beta/alpha could serve as a diagnostic and prognostic marker in patients with ccRCC.

Protein expression profile related to cisplatin resistance in bladder cancer cell lines detected by two-dimensional gel electrophoresis.

We used a proteomic approach to compare the differentially regulated protein expression profiles of cisplatin-naïve and cisplatin-resistant bladder cancer cell lines to screen candidate molecules related to cisplatin resistance. The cisplatin-resistant cell line T24 was established by the stepwise exposure of T24 cells to up to 40 µM of cisplatin. We performed a comprehensive study of protein expression in bladder cancer cell lines that included cisplatin-naïve (T24) and cisplatin-resistant cells (T24CDDPR) by means of agarose two-dimensional gel electrophoresis followed by analysis of liquid chromatography tandem mass spectroscopy. We identified 25 obviously different spots for T24 and T24 CDDPR. Seven spots had increased expression and 18 spots had decreased expression in T24CDDPR compared to those in T24. Cytoskeletal proteins and enzyme modulators were prominent among differential proteins. Of the 25 proteins, we selected HNRNPA3, PCK2, PPL, PGK1, TKT, SERPINB2, GOT2, and EIF3A for further validation by Western blot. HNRNPA3, PGK1, TKT, and SERPINB2 had more than 1.5-times incremental expression in T24CDDPR compared to that in T24. PCK2 and PPL expressions were decreased less than 20% in T24CDDPR compared to that in T24. The results of 25 new proteins in this study could be valuable and could lead to the development of a new molecular marker.

Establishment of a Strategy for the Discovery and Verification of Low-Abundance Biomarker Peptides in Plasma Using Two Types of Stable-Isotope Tags.

Serum and plasma contain thousands of different proteins and peptides, which can provide valuable information about the numerous processes that take place within the body. However, detailed analysis of proteins and peptides in serum and plasma remains challenging due to the presence of many high-abundance proteins, the large dynamic range of protein and peptide concentrations, the extensive complexity caused by posttranslational modifications, and considerable individual variability. In particular, detailed analysis and identification of native peptides is extremely difficult due to the tremendous variety of cleavage possibilities and posttranslational modifications, which results in extremely high complexity. Therefore, widely ranging searches based on peptide identification are difficult. Herein, we describe the highly accurate and sensitive quantitative analysis of over 2,500 peptides with the concentration limit of about 10 pM. The strategy combined isobaric tag labeling, amine-reactive 6-plex tandem mass tag labeling, and a modified differential solubilization method for high-yield peptide extraction [Saito, T. et al. J. Electrophoresis 2013 57: 1-9]. Using this strategy, we quantitatively analyzed six pooled plasma samples (three pre-surgery and three post-surgery) to discover potential candidate biomarker peptides of renal cell carcinoma. The concentrations of 27 peptides were found to be altered following surgery. A preliminary validation study was conducted using about 80 plasma samples to demonstrate the possibility that even unidentified potential candidate biomarker peptides can be verified using the isotope tag/dimethyl labeling method. We also discuss technical consideration and potential of this strategy for facilitating native peptide research.

Radiotherapy for oligometastases and oligo-recurrence of bone in prostate cancer.

Purpose. To retrospectively evaluate the clinical significance of radiotherapy for oligometastases of bone in prostate cancer (PCa). Methods and Materials. Between 2003 and 2008, 35 PCa patients with oligometastases of bone were treated with radiotherapy. Results. The median radiotherapy dose was 40 Gy. The 3-year overall survival rates for all patients, for patients that received a radiotherapy dose of ≥40 Gy (n = 21) and for those that received <40 Gy (n = 14), were 77.2%, 90.5%, and 50.0%, respectively. Fourteen out of 16 patients (87.5%) who had pain were improved 1 month after radiotherapy. The median duration of pain relief was 12 months. Pathological fracture and spinal cord compression (SCC) were not seen at the treated sites but developed at nonirradiated sites in three patients (8.6%) and in one patient (2.8%), respectively. Although the high-dose group (≥40 Gy) achieved better survival than the low-dose group (<40 Gy), it was not independent prognostic factor in multivariable analysis. Conclusions. Radiotherapy of bone oligometastases in PCa was effective for long-term pain relief. Pathological fracture and SCC were not seen at the treated sites. A larger clinical trial is warranted to study the actual benefit following radiotherapy for oligometastases of bone in PCa.

Prevalence of fluoroquinolone-resistant Escherichia coli before and incidence of acute bacterial prostatitis after prostate biopsy.

OBJECTIVE: To study the prevalence of fluoroquinolone-resistant Escherichia coli before transrectal ultrasound (TRUS)-guided prostate biopsy and prospectively analyze the rates of infective complications after biopsy in patients receiving fluoroquinolone prophylaxis. E. coli is the pathogen most commonly associated with infections after TRUS-guided prostate biopsy, and the prevalence of fluoroquinolone-resistant E. coli is increasing. METHODS: We analyzed the prospective data from 100 patients who underwent TRUS-guided prostate biopsy from April to December 2010. A stool culture was obtained 1 month before biopsy. Patients received 500 mg levofloxacin orally once daily for 3 days, beginning 2 hours before biopsy. All biopsies were performed as outpatient procedures. RESULTS: Of the 100 patients, 13 (13%) had a stool culture positive for fluoroquinolone-resistant E. coli. In 4 (31%) of these 13 patients, acute bacterial prostatitis was detected after TRUS-guided prostate biopsy. Of the 87 patients whose stool culture was negative for fluoroquinolone-resistant E. coli, none had acute bacterial prostatitis. All 13 infected patients were treated with carbapenems immediately after diagnosis of prostatitis and made a complete recovery. CONCLUSION: Prophylactic fluoroquinolone is still effective in preventing acute bacterial prostatitis after TRUS-guided prostate biopsy. The incidence is relatively low in patients with fluoroquinolone-sensitive E. coli. However, the prevalence of fluoroquinolone-resistant E. coli is about 13% in this population. Stool cultures for the detection of fluoroquinolone-resistant E. coli might be obtained before TRUS-guided prostate biopsy.

Combination of gemcitabine and paclitaxel is a favorable option for patients with advanced or metastatic urothelial carcinoma previously treated with cisplatin-based chemotherapy.

OBJECTIVE: To evaluate the efficacy and toxicity of a gemcitabine and paclitaxel regimen for patients with advanced urothelial carcinoma who had previously been treated with methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy, and to determine the prognostic factors for survival in second-line chemotherapy. METHODS: From June 2005 to April 2010, 24 eligible patients who had previously been treated with methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy were enrolled in this study. Patients received paclitaxel 200 mg/m(2) on Day 1 and gemcitabine 1000 mg/m(2) on Days 1, 8 and 15. The gemcitabine and paclitaxel regimen was repeated every 3 weeks. Patients were evaluated every two cycles by imaging study. RESULTS: Ten of 24 patients (42%) had major response to the gemcitabine and paclitaxel regimen, including 2 patients (8%) who had complete response. Median survival time and median progression-free survival were 12.4 and 6.1 months, respectively. Good performance status and major response to first-line methotrexate, vinblastine, doxorubicin and cisplatin treatment were significant predictors of overall survival and progression-free survival. Grade 3 or 4 neutropenia occurred in 16 patients (67%), but there were no severe infections. There were no treatment-related deaths. CONCLUSIONS: Gemcitabine and paclitaxel chemotherapy had favorable benefit and safety profiles, and the regimen is recommended as a potential second-line chemotherapy for advanced or metastatic urothelial carcinoma previously treated with methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy.

Comparison of prophylactic naftopidil, tamsulosin, and silodosin for 125I brachytherapy-induced lower urinary tract symptoms in patients with prostate cancer: randomized controlled trial.

PURPOSE: To compare the efficacy of three α(1A)/α(1D)-adrenoceptor (AR) antagonists--naftopidil, tamsulosin, and silodosin--that have differing affinities for the α(1)-AR subtypes in treating urinary morbidities in Japanese men with (125)I prostate implantation (PI) for prostate cancer. METHODS AND MATERIALS: This single-institution prospective randomized controlled trial compared naftopidil, tamsulosin, and silodosin in patients undergoing PI. Patients were randomized and received either naftopidil, tamsulosin, or silodosin. Treatment began 1 day after PI and continued for 1 year. The primary efficacy variables were the changes in total International Prostate Symptom Score (IPSS) and postvoid residual urine (PVR). The secondary efficacy variables were changes in IPSS storage score and IPSS voiding score from baseline to set points during the study (1, 3, 6, and 12 months). RESULTS: Two hundred twelve patients were evaluated in this study between June 2006 and February 2009: 71, 70, and 71 patients in the naftopidil, tamsulosin, and silodosin groups, respectively. With respect to the primary efficacy variables, the mean changes in the total IPSS at 1 month after PI in the naftopidil, tamsulosin, and silodosin groups were +10.3, +8.9, and +7.5, respectively. There were significantly greater decreases with silodosin than naftopidil at 1 month in the total IPSS. The mean changes in the PVR at 6 months were +14.6, +23.7, and +5.7 mL in the naftopidil, tamsulosin, and silodosin groups, respectively; silodosin showed a significant improvement in the PVR at 6 months vs. tamsulosin. With respect to the secondary efficacy variables, the mean changes in the IPSS voiding score at 1 month in the naftopidil, tamsulosin, and silodosin groups were +6.5, +5.6, and +4.5, respectively; silodosin showed a significant improvement in the IPSS voiding score at 1 month vs. naftopidil. CONCLUSIONS: Silodosin has a greater impact on improving PI-induced lower urinary tract symptoms than the other two agents.

14-3-3 protein beta/alpha as a urinary biomarker for renal cell carcinoma: proteomic analysis of cyst fluid.

Although various samples, including tissue, cells, serum, and urine, from patients with renal cell carcinoma (RCC) have been analyzed, biomarkers with diagnostic value have yet to be identified. We used a proteomics approach to analyze cyst fluid in cases of cyst-associated RCC to identify accessible and abundant proteins that are overexpressed and/or secreted by RCC cells. Proteins in the cyst fluid were separated by reverse-phase high-performance liquid chromatography and agarose two-dimensional gel electrophoresis and were identified by tandem mass spectrometry. We conducted a National Center for Biotechnology Information search and a MEDLINE search to predict the function of these identified proteins and to select a tumor-marker candidate protein. Our search resulted in the identification and selection of the differentially regulated protein known as 14-3-3 protein beta/alpha, which was overexpressed in cyst fluid from cyst-associated RCC but has not been previously associated with RCC. We then measured its incidence through Western blotting of various normal and RCC samples (serum, urine, tissue, and cyst fluid). The expression levels of 14-3-3 protein beta/alpha were higher in urine samples from patients with RCC than in samples from healthy volunteers. Receiver operating characteristic (ROC) curve analyses were performed to assess this potential biomarker; these data (area under the ROC curve value was 0.8813) indicate a high degree of accuracy for this screening method. 14-3-3 Protein beta/alpha may be a diagnostically useful biomarker for early diagnosis of RCC.

Profilin 1 overexpression in renal cell carcinoma.

OBJECTIVES: To gain information about overexpressed antigens in renal cell carcinoma (RCC) by using a chemical proteomics approach. METHODS: RCC cell line 769P was cultured and proteome analysis was subsequently carried out in the culture supernatants. By using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and tandem mass spectrometry (LC-MS/MS), proteins in the culture supernatants were searched. A MEDLINE search to define the functions of the identified proteins was carried out. RESULTS: Four differentially regulated proteins (profilin 1, amyloid beta A4 protein [APP], proprotein convertase subtilisin/kexin type 1 inhibitor [ProSAAS], galectin-3-binding protein [LGALS3BP]) were selected. These were not overexpressed in normal kidney tissue or reported in RCC. Their levels were measured through western blotting of normal kidney and RCC tissues. No differences were observed in the expression levels of APP, ProSAAS or LGALS3BP between RCC and normal kidney tissues. Profilin 1 was overexpressed in RCC tissue. On the basis of this observation, an immunohistochemical analysis of profilin 1 in normal kidney and RCC tissues was carried out. In normal tissues, tubules that were sources of RCC stained positive for profilin 1. In RCC tissue, in contrast, the stromal cells in the tumors stained positive. CONCLUSIONS: Profilin 1 can be a key element in the pathological processes of RCC, such as tumorigenesis and/or tumor growth. Thus, it has the potential to serve as a diagnostic or progression biomarker and therapeutic target in RCC.

Cost comparison of curative therapies for localized prostate cancer in Japan: a single-institution experience.

PURPOSE: In addition to open surgery, curative therapies for prostate cancer now include endoscopic surgery and radiation therapies. Because of the expansion and subdivision of treatment methods for prostate cancer, the medical fee point schedule in Japan was revised in fiscal year 2006. We examined changes in medical income and expenditure after this revision of the medical fee system. MATERIALS AND METHODS: We studied income and expenditure, after institution of the new medical fee schedule, for the five types of therapies for prostate cancer performed at our hospital: two surgical therapies (radical retropubic prostatectomy and laparoscopic prostatectomy) and three radiation therapies (three-dimensional conformal radiation therapy, (192)Ir high-dose-rate brachytherapy, and (125)I low-dose-rate brachytherapy). RESULTS: Low-dose-rate brachytherapy was found to be associated with a profit of yen199 per patient. Laparoscopic prostatectomy, a highly advanced medical treatment that the fee revision changed from a partially insured to an insured procedure, yielded a profit of yen75,672 per patient. However, high-dose-rate brachytherapy was associated with a loss of yen654,016 per patient. CONCLUSION: Given the loss in hospital income per patient undergoing high-dose-rate brachytherapy, the medical fee point system for this procedure should be reassessed.

Varicocele complicating spontaneous arteriovenous fistula.

We describe herein a rare case of a varicocele complicating spontaneous arteriovenous fistula. A 40-year-old man was referred to our hospital in November 2006, complaining of a non-tender mass in the left scrotum at the age of 15 and thereafter. On examination, his left scrotum revealed a large varicocele, but no manifest superficial thrill was noted. Scrotal ultrasonograpy revealed approximately 7 cm large varicocele. Computed tomography angiography revealed the existence of an arteriovenous fistula between the left testicular artery and the veins of the left pampiniform plexus. We laparoscopically carried out internal spermatic vessels ligation under the diagnosis of a varicocele complicating a spontaneous arteriovenous fistula. The postoperative course was uneventful. At 18 months postoperatively, the varicocele and fistula had not recurred.

[Spontaneous migration of a metal clip into renal pelvis after laparoscopic pyeloplasty: a case report].

Migration of surgical materials into the urinary tract is very rare. We present a case of spontaneous migration of a metal clip into renal pelvis after laparoscopic pyeloplasty. A 44-year-old woman who had a long history of multiple sclerosis presented with symptomatic left hydronephrosis due to ureteropelvic junction (UPJ) obstruction. Since antegrade endopyelotomy was unsuccessful, the patient underwent laparoscopic Anderson-Hynes pyeloplasty. The UPJ was wrapped with thick inflammatory tissue and a crossing vessel that firmly adhered to the UPJ was found and dissected. Metal clips were used for hemostasis. Although the hydronephrosis was improved and flank pain was completely dissolved, a stone was identified in the pelvis 22 months after the surgery. The stone was formed around a metal clip that had been possibly migrated into the renal pelvis. Transureteral lithotripsy was performed using an 8F ureterofiberscope and a clip was removed.

Case of seminoma with possible spontaneous regression without extragonadal metastatic lesion.

We present an extraordinarily rare finding of a testicular seminoma apparently in the process of spontaneous regression without accompanying metastatic lesion. A 35-year-old man visited our institute for persistent scrotal induration after the administration of antibiotics for several weeks. Ultrasonography and magnetic resonance imaging showed a capsulized tumor in his left atrophic testicle, without other visceral tumor or lymphadenopathy. We performed left radical orchiectomy. Histological examination revealed a fibrotic tumor with a small area of pure seminoma apparently undergoing spontaneous regression, and an intratubular germ cell neoplasia, unclassified, occurring diffusely. The patient is free of disease at 1 year after surgery.

[Case of local recurrence of the periurethral proximal-type epithelioid sarcoma successfully treated by repeated regional excision].

Proximal-type epithelioid sarcomas are rare soft tissue neoplasms occuring in the soma or thigh and often repeat recurrence and metastasis. We present a case of locally recurrenced proximal-type epithelioid sarcoma that could be treated by regional excision alone. A 62-year-old man visited our institute for a growing mass in the perineal region. Computed tomography (CT) showed a periurethral tumor 22 x 13 mm in diameter in the perineal region. The tumor was excised regionally, and the pathological examination with immunohistochemical staining revealed that the tumor was proximal-type epithelioid sarcoma. Local recurrence of the tumor occurred 2 years 7 months later without any metastatic lesion, and regional excision was performed again. Pathological diagnosis was proximal type epithelioid sarcoma and it was identical to the primary tumor. The patient is free of the disease 1 year after the second surgery of the tumor.

[Late-onset urethrorectal fistula after laparoscopic radical prostatectomy: report of a case].

Urethrorectal fistula is a relatively rare disease. The most frequent cause of acquired urethrorectal fistulas is known to be iatrogenic complications, such as rectal injuries during the prostate operations. Rectal injuries are usually noticed during the operation and the majority can be repaired in situ. We report a case of late-onset urethrorectal fistula that lacked obvious rectal injury during the operation. Ischemic change or heat denaturation of rectal wall may be the potential cause of the present urethrorectal fistula.