[CASE REPORT: COMPLETE RESECTION OF RETROPERITONEAL CYSTIC LYMPHANGIOMA AND SURROUNDING ORGANS].

A 65-year-old man was admitted to our institution with vomiting and right flank pain. Computed tomography (CT) imaging showed a 21-cm retroperitoneal multilocular cystic tumor which had been identified four years previously. It had increased from 17 to 21 cm. The initial diagnosis was cystic lymphangioma because it was a clear cystic tumor without a boundary or a solid component in the first CT, but later CT revealed an unclear boundary with surrounding organs suggesting malignancy. We decided to resect the tumor because it was symptomatic and might be malignant. The tumor was then resected along with surrounding organs because invasion was suspected. Pathological findings indicated a diagnosis of cystic lymphangioma with chronic inflammation and confirmed complete resection of the tumor. The patient has remained free of recurrence at one year after surgery. This experience indicates that cystic lymphangioma should be completely resected to prevent recurrence.

Current work environments: What problems are being faced by Japanese urologists?

Computer technology has contributed to innovative progress in industrial infrastructures and has had a major influence on various work environments. Evaluations of work environments are routinely carried out in Western countries, but historically there has been resistance to such evaluations in Japan. In this mini-review, we discuss the current work environments of urologists in Japan. The number of urologists has increased each year, and the population density of urologists was 5.4 (per 100 000 people) in 2014. The average age of urologists in Japan was 48.9 years, and the percentage of female urologists was just 5.3%. Additionally, the geographic distribution of urologists was uneven in Japan. From projections based on population dynamics, the need for more urologists in the near future will probably increase. Because medical environments vary depending on the country, it is necessary to understand current work environments in greater detail initially. Furthermore, we should determine original measures for the establishment of satisfactory urological work environments in Japan.

[POSTERIOR PERIURETHRAL ABSCESSES DUE TO NEISSERIA GONORRHOEAE POSED DIAGNOSTIC DIFFICULTIES].

Posterior periurethral abscesses due to Neisseria gonorrhoeae are rare and thus difficult to diagnose and treat. We diagnosed this type of abscess using MRI and treated it conservatively.A 27-year-old man presented with perineal discomfort that had persisted for 1 week. Physical and CT findings indicated a prostate abscess, but MRI after admission revealed a multilocular mass in the posterior periurethra and polymerase chain reaction was positive for Neisseria gonorrhoeae. The posterior periurethral abscess was treated with Ceftriaxone and drainage via a cystostomy. This strategy improved the inflammation and CT confirmed the disappearance of the abscess from start of therapy in 43 days.

Endoscopic Treatment of Intrauterine Device Migration into the Bladder with Stone Formation.

Background: An intrauterine device is commonly used for contraception globally. Although intrauterine device placement is an effective and safe method of contraception, migration into the bladder with stone formation is a rare and serious complication. The management approaches for an intrauterine device embedded in the bladder include endoscopic procedures and open surgical removal. In this study, we report the case of a patient with recurrent urinary tract infection associated with intrauterine device migration and urolithiasis, who successfully underwent endoscopic treatment combined with laser fragmentation. Case Presentation: A 22-year-old woman presented to our hospital with a 1-month history of lower abdominal pain, hematuria, and pain on urination. Transvaginal ultrasound showed a hyperechoic lesion in the bladder. A plain abdominal radiograph showed the presence of a T-shaped intrauterine device with calculus formation in the pelvis. CT revealed a vesical stone fixed to the top of the bladder wall, and there was no vesicovaginal fistula formation. She had undergone intrauterine device insertion several years previously. Cystoscopy confirmed the diagnosis. She underwent endoscopic lithotripsy, and the intrauterine device was extracted from the bladder wall. Repair of the bladder wall and disappearance of symptoms were confirmed. Conclusion: Endoscopic treatment combined with laser fragmentation of stones surrounding a migrated intrauterine device should be considered as a minimally invasive approach, which can be performed safely.

[A Case of Dedifferentiated Liposarcoma of the Spermatic Cord].

A 63-year-old man was referred to our department because of painless hard mass in the right inguinal region. Abdominal computed tomography (CT) showed right spermatic cord mass measuring 25 mm in diameter. We performed right high orchiectomy. Histopathological diagnosis was dedifferentiated liposarcoma, which included myofibroblast components. He was alive 3 years postoperatively without recurrence.

Further enhancement of FR901469 productivity by co-overexpression of cpcA, a cross-pathway control gene, and frbF in fungal sp. No. 11243.

FR901469 is a secondary metabolite with antifungal activity, produced by fungal sp. No. 11243. In our previous study, we constructed the frbF overexpression mutant (TFH2-2) from the wild-type strain. FR901469 productivity of TFH2-2 was 3.4 times higher than that of the wild-type strain. To further enhance FR901469 productivity in TFH2-2, we attempted to find genes from the genome that limited the productivity as bottlenecks in this study. Based on both correlation analysis of gene expression level against FR901469 productivity and genome annotation information, the cross-pathway control gene A (cpcA) was most predicted as the bottleneck. The cpcA and frbF co-overexpression mutant named TFCH3 was then constructed from TFH2-2. As a result, FR901469 productivity of TFCH3 was enhanced at 1.8 times higher than that of TFH2-2. Transcriptome analysis revealed that many genes involved in amino acid biosynthesis and encoding tRNA ligases were significantly upregulated in TFCH3, which implied increase of amino acids as the substrates of FR901469 would be a reason of further productivity enhancement.

[LAPAROSCOPIC LYMPHADENECTOMY FOR POSTOPERATIVE LYMPH-NODE METASTASIS OF RENAL MUCINOUS TUBULAR AND SPINDLE CELL CARCINOMA: A CASE REPORT].

We describe renal mucinous tubular and spindle cell carcinoma (MTSCC) that metastasized to the lymph nodes seven years after radical nephrectomy. An 80-year-old man was admitted for treatment of a right renal tumor. A 6.5×6.0-cm tumor in the right kidney (cT1bN0M0) revealed by abdominal computed tomography was treated by laparoscopic radical nephrectomy. The pathological findings at that time suggested papillary renal cell carcinoma type 1. Imaging findings seven years later revealed enlarged pre-caval and right external iliac lymph nodes indicative of delayed metastasis, and these were treated by laparoscopic lymphadenectomy. The pathological findings and re-evaluation of the primary tumor suggested MTSCC. The patient remains free of metastasis at 24 months of follow-up. MTSCC has been a distinct entity in the World Health Organization classification of kidney tumors since 2004. Tumors consist of tubules and cords separated by pale mucinous material in some areas, whereas others have dense cellularity without significant mucin. They are usually of low malignant potential, and metastasis has rarely been reported. To our knowledge, this is the first report of MTSCC with retroperitoneal lymph node metastasis treated by lymphadenectomy.

Identification of a putative FR901469 biosynthesis gene cluster in fungal sp. No. 11243 and enhancement of the productivity by overexpressing the transcription factor gene frbF.

FR901469 is an antifungal antibiotic produced by fungal sp. No. 11243. Here, we searched for FR901469 biosynthesis genes in the genome of No. 11243. Based on the molecular structure of FR901469 and endogenous functional motifs predicted in each genomic NRPS gene, a putative FR901469 biosynthesis gene cluster harboring the most plausible NRPS gene was identified. A transcription factor gene, designated frbF, was found in the cluster. To improve FR901469 productivity, we constructed a strain in which frbF was overexpressed and named it TFH2-2. FR901469 productivity of TFH2-2 was 3.4 times higher than that of the wild-type strain. Transcriptome analysis revealed that most of the genes in the putative FR901469 biosynthesis gene cluster were upregulated in TFH2-2. It also showed that the expression of genes related to ergosterol biosynthesis, ß-1,3-glucan catabolism, and chitin synthesis was inclined to exhibit significant differences in TFH2-2.

Genome Sequence of Fungal Species No.11243, Which Produces the Antifungal Antibiotic FR901469.

Fungal species No.11243 was originally isolated from a decayed leaf sample collected in Kyoto, Japan. It produces FR901469, a 1,3-beta-glucan synthase inhibitor. The genome sequence of No.11243 was determined and annotated to obtain useful information for improving productivity of the effective antifungal agent FR901469.

Efficacy of a thermoexpandable metallic prostate stent (Memokath) in elderly patients with urethral obstruction requiring long-term management with urethral Foley catheters.

AIM: 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. METHODS: 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. RESULTS: 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 was <50 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. CONCLUSIONS: 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.

[Marked efficacy of multimodality therapy for ureteral cancer producing granulocyte colony-stmimulating factor].

A 69-year-old man was admitted with the chief complaint of macroscopic hematuria. Computerized tomography (CT) and ureteroscopy showed right ureter cancer. Right nephroureterectomy and partial cystectomy were performed. Histological examination revealed urothelial carcinoma of ureter (Grade3, pT3, INFbeta, ly1). The patient underwent two courses of adjuvant chemotherapy with gemcitabine and cisplatin. Three months later, abdominal CT showed a mass in his right obturatorius area. The patient's white blood cell count was 34,140 cells/microl. Additionally serum analysis revealed high value of granulocyte colony stimulating factor (G-CSF), 596 pg/ml with no obvious focus. After being diagnosed with recurrent ureteral cancer producing G-CSF, the patient underwent secondary chemotherapy with gemcitabine and docetaxel. After three courses of chemotherapy, CT revealed a marked decrease in tumor size, and the value of G-CSF declined at 31 pg/nl. Subsequently, radiotherapy (60 Gy) was administered. The patient has been alive for 16 months.

[Balanitis xerotica obliterans with phimosis in elderly patients presenting with difficulty in urination].

Eight elderly patients (average age 76.1±4.3 years) with balanitis xerotica obliterans (BXO) accompanied by phimosis presented with difficulty in urination. Preoperative average international prostate symptom score, average maximum urinary flow rate, and average volume of residual urine were 20.7±6.3 points (n＝8), 5.1±3.6 ml/s (n＝5), and 85.4±77.3 ml (n＝8), respectively. Some of the patient's complaints, such as severe dribbling of urine, urinary stream division, and ballooning of the foreskin, were not included in the items of the major questionnaire on urination. Dorsal incision and circumcision was performed in all patients, and all were pathologically diagnosed with BXO. Meatoplasty was performed in one patient with a meatal stenosis. No coexistence of penile cancer was observed. Statistically significant improvements were observed in subjective and objective findings after treatment. In conclusion, BXO with phimosis in elderly patients should be considered as a cause of lower urinary tract symptoms.

Sunitinib treatment for refractory malignant pheochromocytoma.

We report the clinical response and adverse events of a female patient treated for recurrent malignant pheochromocytoma using the tyrosine kinase inhibitor sunitinib. A 41-year-old woman underwent adrenectomy and nephrectomy forpotentially malignant adrenal pheochromocytoma. Fifty-four months after surgery, abdominal computed tomography (CT) and Iodine-131 metaiodobenzylguanidine((131)I-MIBG) scintigraphy revealed multiple tumors in the liver. Two chemotherapy protocols were administered in succession (first line: cyclophosphamide/vinblastine/dacarbazine; second line: cisplatin/docetaxel/ifomide). Despite these treatments, however, the tumors continued to progress. Treatment with sunitinib was initiated, but the patient quickly developed critical hypertension caused by tumor lysis syndrome. The sunitinib dose was reduced, and a partial response, as defined by the Response Evaluation Criteria in Solid Tumors (RECIST), was observed after 6 treatment cycles. Moreover, no severe adverse events occurred during this lower-dose sunitinib treatment. Unfortunately, sunitinib treatment became unaffordable for the patient, who eventually resorted to palliative care and died 37 months later. This case study is consistent with previous reports indicating that appropriate doses of sunitinib can induce a partial antitumor response in patients with refractory pheochromocytoma.

Complete remission of renal cell carcinoma with lung metastases in two hemodialysis patients after low-dose interferon therapy.

A standard immunotherapy strategy for metastatic renal cell carcinoma (RCC) in dialysis patients has yet to be established. In this study, we report complete remission of RCC with lung metastases in 2 hemodialysis patients after low-dose interferon therapy (Sumiferon® 3 × 106 international unit 3 times a week). These results suggest that interferon therapy is important for clear cell RCC with lung metastases in dialysis patients, even in the era of molecular-targeted therapies.

Changes in diffusion-weighted images for visualizing prostate cancer during antiandrogen therapy: preliminary results.

OBJECTIVES: To assess the potential of diffusion-weighted imaging (DWI) for monitoring the response to antiandrogen therapy in prostate cancer. METHODS: After patients had undergone 6 months of antiandrogen therapy, we investigated the time-course changes in findings obtained from DWI compared to the findings obtained from T(2)-weighted (T(2)W) images, transrectal ultrasound (TRUS), and prostate-specific antigen (PSA) kinetics. RESULTS: The time-course changes in T(2)W images, TRUS, and PSA kinetics following antiandrogen therapy in the present study were consistent with previous reports. In all patients, the posttreatment hypointense signals on DWI were attenuated. Identification of tumor location was difficult on the basis of changes in magnetic resonance imaging findings following antiandrogen therapy due to the remarkable reduction of the total prostatic volume. Three patients exhibited residual tumors that were easily visualized, and apparent diffusion coefficient values increased after treatment in these patients. However, in 1 patient with neuroendocrine differentiation during antiandrogen therapy, DWI findings revealed that the hypointense signal in the prostate became progressively more pronounced. However, this case showed a low PSA recurrence without remarkable changes in the T(2)W images. CONCLUSIONS: The preliminary results suggest that DWI is useful to understand clinical significance of PSA kinetics in patients with low PSA recurrence during antiandrogen therapy.

[A case of testicular tumor with inferior vena cava thrombus].

A 31-year-old man presented with edema in left lower leg and dyspnea. Computed tomographic scanning detected a right testicular tumor, multiple lung nodules, and inferior vena cava (IVC) thrombus. After insertion of an IVC filter, high inguinal orchiectomy was performed after the first combination chemotherapy. Pathological examination demonstrated an embryonal carcinoma with vascular invasion and direct tumoral extension into the right spermatic cord. According to our survey, this is the 14th case of testicular tumor with IVC thrombus in Japan.

The negative-balance isolated pelvic perfusion method using ultrahigh-dose cisplatin for invasive bladder cancer with poor risk.

BACKGROUND: Our aim was to evaluate the clinical significance of the negative-balance isolated pelvic perfusion (NIPP) method using ultrahigh-dose cisplatin (CDDP) for ten cases of invasive bladder cancer with poor risk such as high-grade cancer, advanced clinical stage, or appearance of hydronephrosis. METHODS: A CDDP dosage of 200-300 mg/body was used under the NIPP method. To confirm safety and efficacy, peripheral blood, pelvic arterial blood, pelvic venous blood, and urine were collected for sampling of the platinum (Pt) concentrations. These samples were investigated and compared with those following previous intraarterial chemotherapy sessions. RESULTS: The Pt concentrations in pelvic blood under intraarterial chemotherapy and NIPP were 5.97 ± 2.06 and 24.15 ± 4.61 µg/ml, respectively. By contrast, the Pt concentration in peripheral blood under NIPP was half the level under conventional intraarterial chemotherapy. No severe adverse events were found in terms of gastrointestinal and hematological toxicity, but renal function was impaired in some cases. Pathological or surgical complete response (CR) was achieved in five of ten cases (50%) in spite of the group being poor risk, and bladder preservation was possible in all the CR cases. Patients with CR experienced survival in all terms of observation. CONCLUSIONS: The NIPP method was able to deliver high levels of CDDP concentration in pelvis cavity without severe adverse events. The NIPP method makes it possible to achieve CR for the patients with invasive bladder cancer with poor risk who rejected cystectomy.

G2/M accumulation in prostate cancer cell line PC-3 is induced by Cdc25 inhibitor 7-chloro-6-(2-morpholin-4-ylethylamino) quinoline-5, 8-dione (DA 3003-2).

Cdc25 phosphatases are dual-specific phosphatases that play a role in cell cycle progression. In many human cancers, Cdc25 phosphatases are overexpressed as compared with normal tissues. In addition, overexpression of Cdc25 phosphatases in prostate cancer is correlated with disease progression. The antiproliferative efficacy of Cdc25 phosphatase inhibitor 7-chloro-6-(2-morpholin-4-ylethylamino) quinoline-5, 8-dione (DA 3003-2) was investigated in the PC-3 asynchronous human prostate cancer cell line using a cell-based assay. The time course changes in cell cycle distribution and the modulation of cell cycle regulators after DA 3003-2 administration were analyzed using the MTT assay. We found that the relative IC(50) of DA 3003-2 was 2-fold lower as compared with its congener (2-mercaptoethanol)-3-methyl-1, 4-naphthoquinone (NSC 672121). Asynchronous PC-3 cells accumulated in the G2/M phase at 24 h after treatment with 10 µM DA 3003-2 or 20 µM NSC 672121, which represent IC(70) concentrations. Treatment of cells with DA 3003-2 caused hyperphosphorylation of Cdc2 tyr(15) in cyclin B(1) and cyclin A complexes. DA 3003-2 did not downregulate the protein expression levels of Cdc25s, cyclins and cyclin-dependent kinases (Cdks). To conclude, after DA 3003-2 administration asynchronous PC-3 cells accumulated in the G2/M phase, with hyperphosphorylation of the G2/M cyclin-Cdk complex.

Neuroendocrine differentiation of localized prostate cancer during endocrine therapy.

A 74-year-old male was treated with endocrine therapy for localized prostate cancer. After 25 months he complained of a swollen neck, and was diagnosed with prostate cancer with lymph node metastasis of neuroendocrine differentiation. Neuroendocrine differentiation without elevation of conventional tumor markers is rare during the initial recurrent course of localized prostate cancer.