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.

[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.

[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.

[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.

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.

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.

[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.

[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.

[Testicular metastasis and local recurrence of renal cell carcinoma after nephron-sparing surgery in von Hippel-Lindau disease].

Bilateral nephron-sparing surgery was performed on a 56-year-old man with von Hippel-Lindau disease as initial therapy for renal cell carcinoma (RCC). Two years after the surgery, an abdominal computerized tomography (CT) scan revealed local recurrence of RCC. The patient was admitted to our hospital after another CT scan three years later that indicated aggravation of the cancer. On physical examination, he complained of swelling of the scrotum. The patient was diagnosed with an intra-scrotal malignant tumor and local recurrence of RCC. We performed high orchiectomy and nephrectomy. The testicular tumor was diagnosed as testicular metastasis of RCC on pathological examination.

[The clinical status of prostate cancer in elderly patients 75 years of age or older in the Kitamurayama District of Yamagata Prefecture, Japan].

To evaluate the present status of prostate cancer in patients 75 years of age or older, we reviewed clinical characteristics of prostate cancer in patients from the Kitamurayama Hospital. The number of symptomatic advanced cases was greater in patients > or = 75 years old compared with patients < or = 74 years old. However, no significant difference in cause-specific survival rate was found between the two groups. In the cases examined, the difference in biological characteristics between groups did not affect the prognosis. On the other hand, for patients > or = 75 years old, improvement of urinary retention was low, and the incidence of adverse drug responses to endocrine therapy, such as dementia and thrombosis, was high. We recognize the necessity of a comprehensive medical plan that attaches importance to quality of life and safety for the treatment of patients over 75 years old with prostate cancer.

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.

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.

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.

[A case of granulomatous orchitis].

A 66-year-old man came to us with a chief complaint of painful right scrotal swelling. The right testis was enlarged on the ultrasound gray scale, but the inside was homogeneous. A power Doppler ultrasound showed slightly increased vascular flow in the periphery of the right testis. As the soluble IL-2 receptor was 527 U/ml (normal: 220-530 U/ml), we considered malignant lymphoma and performed high orchiectomy. On pathological examination, the tumor was diagnosed as granulomatous orchitis. To our knowledge, this is the 21st case in Japan.

[Production of granulocyte colony-stimulating factor and parathyroid hormone-related protein in squamous cell carcinoma of the renal pelvis accompanied with inferior vena cava thrombus].

A 54-year-old man with general fatigue and lumbago was admitted for further examination of hypercalcemia and leukocytosis. CT showed a huge renal tumor and extension of the tumor thrombus to the inferior vena cava (IVC). Moreover, the serum granulocyte colony-stimulating factor (G-CSF) and the C-terminal of parathyroid hormone-related protein (PTHrP) were elevated. Under the diagnosis of advanced renal tumor, we performed nephro-ureterectomy and throbectomy. Pathological examination revealed squamous cell carcinoma of the renal pelvis. To our knowledge, this is the first case in Japan that of the simultaneous production of G-CSF and PTHrP in squamous cell carcinoma of the renal pelvis accompanied with IVC thrombus.

The carcinogen (7R,8S)-dihydroxy-(9S,10R)-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene induces Cdc25B expression in human bronchial and lung cancer cells.

Cdc25B regulates cell cycle progression and genetic stability. Here, we report that exposure to the environmental carcinogen (7R,8S)-dihydroxy-(9S,10R)-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) causes a marked increase in the expression of Cdc25B mRNA and protein levels in terminal squamous differentiated human bronchial epithelial cells and in lung cancer cells, but not in undifferentiated bronchial cells. In addition, the growth rate of lung cancer cells was increased significantly in comparison with untreated cells after chronic exposure to 0.1 micro M anti-BPDE. Furthermore, increased Cdc25B expression and decreased Cdk1 phosphorylation were observed in anti-BPDE-treated cells. We postulate that the induction of Cdc25B expression in lung cancer cells by the ultimate carcinogen anti-BPDE accelerates the further development of lung carcinogenesis.