Fuminori Satoh

Autocrine expression of neurotrophins and their receptors in prostate cancer

Abstract Previously, it has been demonstrated that the neurotrophins and their receptors are present in human prostate tissue, but neither their functional role nor localization is clearly understood. We studied the expression of neurotrophins and their receptors in prostate cancer. Between 1990 and 1999, 48 prostate cancer specimens were obtained from patients undergoing radical prostatectomy, of whom 25 received neoadjuvant hormonal therapy (NHT) and 23 were untreated. The specimens were analyzed immunohistochemically for neurotrophins (nerve growth factor, brain derived neurotrophic factor, neurotrophin 3, neurotrophin 4/5) and their receptors (TrkA, TrkB, TrkC, p75NTR). Immunohistochemical studies revealed that both benign and malignant prostate gland epithelial cells expressed the neurotrophins and their receptors to various degrees, but no obvious immunopositive reaction was observed in stromal cells. In benign epithelial cells, the neurotrophins were localized to secretory cells and the receptors were localized to basal cells. The neurotrophins, TrkA and TrkC were expressed to a similar extent in prostate cancer specimens obtained from patients both with and without NHT. In contrast, the expression of TrkB was down‐regulated and the expression of p75NTR was up‐regulated in prostate cancer after hormonal therapy. These findings suggest that neurotrophins are secreted by prostate cancer cells in an autocrine fashion. Neurotrophins may be involved, through their receptors, in the escape mechanism from cell death after androgen depletion found in prostate cancer.

Changes of Rat Urinary Bladder during Acute Phase of Spinal Cord Injury

Spinal cord injury (SCI) at Th13 was induced in female Wistar rats, and changes in the urinary bladder were examined during the acute phase of SCI. Wet weights of the spinal bladders increased twofold over controls by 7 days after SCI. Intravesical volumes increased sixfold over control values by day 3, and then decreased 7 days after the injury. Maximal pressure within the bladder decreased in all spinal rats compared with controls. Smooth muscle cells were isolated from the urinary bladder, and their total protein and DNA content were measured by multiparametric cytofluorometry. DNA content of isolated smooth muscle cells decreased by day 3 and remained 7 days after the spinal injury. Total protein content of isolated smooth muscle cells was decreased 1 day after and increased 7 days after the spinal injury, just when spinal reflex of the bladder recovered. These findings suggest that hypertrophy of smooth muscle cells in urinary bladder is related to the activity of peripheral autonomic nerve and that smooth muscle cells already begin to hypertrophy during the spinal shock period to adjust themselves to the new state, that is, the spinal bladder.

Spontaneous Rupture of Adrenal Pheochromocytoma

A 39-year-old woman presented with a 2-year history of frequent episodes of headache, nausea and palpitations. Blood pressure had generally been stable but paroxysmally increased to 180/110 to 210/130 mm. Hg. At hospitalization serum adrenaline was 1,768 pg./ml., serum noradrenaline was 3,449 pg./ml., urine adrenaline was 1,170 g. per day and urinary vanillylmandelic acid was 31.5 mg. per day. Computerized tomography (CT) showed a left adrenal mass (fig. 1, A), and scintigraphy with iodine metaiodobenzylguanidine revealed a high accumulation in the mass. Based on these data left adrenal pheochromocytoma was diagnosed, and 0.5 mg. doxazosin mesylate was started to increase circulatory plasma volume. Subsequently, the patient experienced attacks that were more frequent and severe than before (fig. 2). Severe back pain, palpitations and vomiting persisted for a few minutes several times a day, and she was prescribed sublingual nifedipine and kept on bed rest. Two days after starting -blockade, the patient complained of sudden unbearable pain in the back and chest. Blood pressure increased to 300/180 mm. Hg and pulse rate was 140 beats per minute. Under the diagnosis of hypertensive crisis 5 mg. phentolamine was administered intravenously, and blood pressure decreased to 100/60 mm. Hg. Despite the blood pressure being well controlled, severe pain had steadily progressed from the time of onset. Ruptured pheochromocytoma was diagnosed by CT, which demonstrated a large hematoma in the right retroperitoneal space (fig. 1, B). After cardiac function was checked by electrocardiogram and ultrasonography, 4 units blood was transfused and volume supplementation was performed, while vasodilator phentolamine was administered under continuous monitoring of central venous pressure and direct blood pressure. Left adrenalectomy and drainage of the retroperitoneal hematoma were performed 7 hours after the onset of spontaneous rupture. The patient was placed under general anesthesia after good urine output was confirmed. A hemi-chevron incision was made and transperitoneal adrenalectomy was performed. Blood pressure was maintained at 90/50 to 110/80 mm. Hg and stabilized with phentolamine and alprostadil during the procedure. Hematoma volume was approximately 1,000 gm. and operative time was 120 minutes. Pathological diagnosis was adrenal pheochromocytoma (4 4 5 cm.). A laceration was found between the adrenal gland and tumor. Postoperatively blood pressure normalized without medication, and serum and urine catecholamines returned to normal.

Prediction of alpha-blocker response in men with benign prostatic hyperplasia by magnetic resonance imaging.

OBJECTIVES To assess the value of magnetic resonance imaging (MRI) for predicting the alpha-blocker response in men with symptomatic benign prostatic hyperplasia (BPH) and to examine the relationship between MRI and the area density of smooth muscle cells in BPH. METHODS Twenty-eight men were consecutively enrolled in this study and received tamsulosin 0.2 mg once daily for 4 to 6 weeks. The efficacy of tamsulosin was determined by measuring improvements in the maximum urinary flow rate (Qmax) and International Prostate Symptom Score (IPSS). The patients underwent T2-weighted MRI and were separated into a high (H) or iso-low (IL) group according to the signal intensity of the inner gland of the prostate compared with that of bone marrow of the proximal femur head. The area density of smooth muscle cells was determined using immunostaining with antiactin antibody in 16 prostate specimens. RESULTS IPSS significantly decreased after the administration of tamsulosin from 16 +/- 1 to 8 +/- 1 (n = 28, P <0.0001 ), and 76.7% of the patients had an improved IPSS of 25% or greater. Qmax was significantly increased in group IL (P = 0.03) but not in group H. Of the patients in group IL, 53.3% had a Qmax response (an increase of Qmax of 30% or more); 15.4% did so in group H (P = 0.04). The area density of smooth muscle cells was 48.1 +/- 3.7% in group IL (n = 9) and 36.7 +/- 3.2% in group H (n = 7, P = 0.04). CONCLUSIONS MRI is useful in estimating the area density of smooth muscle cells in the prostate and in predicting Qmax response for alpha-blocker therapy in patients with symptomatic BPH.

Clinical Characteristics of α-Blocker Responders in Men with Benign Prostatic Hyperplasia

Background: Currently, α-blocker is becoming first-line drug therapy for benign prostatic hyperplasia (BPH). Although highly effective results are obtained with this therapy, a difference between the objective and subjective response rates is reported. To prevent unnecessary medical treatment and to predict the α-blocker response, we characterized the clinical features of α-blocker responders in men with BPH. Methods: Twenty-two men were consecutively enrolled in this study and received tamsulosin 0.2 mg once daily for 4–6 weeks. The primary measures of efficacy were maximum urinary flow rate (Qmax) determined from the flow measurements and international prostate symptom score (IPSS). Those with an increase in Qmax of ≧30% from baseline and a decrease in IPSS of ≧25% from baseline were defined as Qmax responders and IPSS responders, respectively. Clinical findings such as age, pretreatment IPSS and Qmax, serum prostate-specific antigen (PSA), total prostate volume, transition zone (TZ) volume, TZ index and T2-weighted magnetic resonance image (MRI) of the prostate TZ were compared between responders and non-responders for both criteria. Results: In 17 of 22 (77.2%) patients IPSS improved by ≧25%. In 9 of 22 (40.9%) patients Qmax improved by ≧30%. There were no differences in clinical findings between IPSS responders and non-responders. On the contrary, Qmax responders showed smaller total prostate and TZ volumes, a smaller TZ index and a lower intensity of the TZ in MRI than Qmax non-responders. Conclusions: Determination of the prostate volume and MRI findings of the inner prostate gland were useful in predicting Qmax responders to the α-blocker in men with BPH. In contrast, there were no clinical characteristics of the IPSS responders. IPSS responders without a Qmax response should be closely followed while continuing the α-blocker therapy for a long duration.

Skeletal-related events in urological cancer patients with bone metastasis: A multicenter study in Japan

Objective:  To investigate the incidence of skeletal‐related events (SRE) in urological cancer patients with bone metastases in Japan.

A Case of Large Solitary Fibrous Tumor in the Retroperitoneum

Solitary fibrous tumor (SFT) is a rare spindle cell neoplasm mainly originated in the pleural cavity. We report here an unusual case of a large SFT in the retroperitoneum. A 27-year-old female complaining of a palpable mass in the right flank with dull pain was admitted to our hospital with the diagnosis of right retroperitoneal tumor. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a large retroperitoneal tumor arising from latissimus dorsi muscle. Surgical findings revealed a partly encapsulated tumor and complete resection of tumor concomitantly with right kidney, 11th and 12th ribs, and diaphragm was performed. Pathological examination demonstrated the tumor to be composed of increased mitotic activity and cellularity of spindle cells with a collagenous matrix. Immunohistochemical staining was positive for CD34, vimentin, and basic fibroblast growth factor (bFGF) and negative for CD31, cytokeratin, desmin, S-100p, smooth muscle actin, Bc1-2, and insulin-like growth factor (IGF) with Ki-67 labeling index of 0.1%. Based on pathological features, diagnosis of SFT in the retroperitoneum was confirmed. To our knowledge, this is the first report of an SFT arising from latissimus dorsi muscle and it is important to include SFT in the differential diagnosis of retroperitoneal tumors that caused considerable diagnostic problems due to its unusual site of origin.

Life-threatening rupture of an external iliac artery pseudoaneurysm caused by necrotizing fasciitis following laparoscopic radical cystectomy: a case report

BackgroundPseudoaneurysms are caused by trauma, tumors, infections, vasculitis, atherosclerosis and iatrogenic complications. In this paper, we report about a patient with rupture of an external iliac artery pseudoaneurysm, which lead to hemorrhagic shock, after undergoing laparoscopic radical cystectomy and extended pelvic lymphadenectomy.Case presentationThe patient was a 68-year-old Japanese male diagnosed with invasive bladder cancer. Laparoscopic radical cystectomy and extended pelvic lymphadenectomy were performed. On postoperative day 12, he developed a high fever and an acute inflammatory response with redness and swelling in the right inguinal region. He was diagnosed with necrotizing fasciitis and underwent debridement. On postoperative day 42, a sudden hemorrhage developed from the open wound in the right inguinal region. He was diagnosed with external iliac artery pseudoaneurysm rupture by computed tomography.ConclusionThese complications occur extremely rarely after cystectomy with pelvic lymphadenectomy. There are no reports to date on these complications following laparoscopic cystectomy with pelvic lymphadenectomy.

Transitional cell carcinoma of the navicular fossa detected human papillomavirus 16

Abstract  We present a rare case of transitional cell carcinoma of the navicular fossa in an elderly man. We detected the expression of human papillomavirus type 16 specific DNA sequence in the tumor using polymerase chain reaction. Human papillomavirus dissemination into the urethra by urethral instrumentation might cause urethral tumors, such as squamous cell carcinoma or condyloma acuminatum, and also transitional cell carcinoma as seen in the present case.

Source of plasma adrenomedullin in a patient with pheochromocytoma receiving hemodialysis

Abstract  A 45‐year‐old man on long‐term hemodialysis (HD) was incidentally discovered to have a pheochromocytoma and underwent successful resection. This patient was normotensive, and had no symptoms suggesting pheochromocytoma. The plasma concentrations of total adrenomedullin (AM‐T) and mature AM (AM‐m) were higher than those in normal controls. To elucidate the source of AM, we measured plasma AM levels by immunoradiometric assay before and 3 weeks after surgery in addition to plasma adrenaline, noradrenaline and dopamine. AM expression was also assessed by immunoblot and immunohistochemical analyses on normal adrenal and tumor tissues. After surgery, elevated plasma adrenaline levels returned to the normal range; however, the levels of AM‐T and AM‐m remained almost the same as the preoperative values. Furthermore, although AM was expressed in both normal adrenal and tumor tissues, the AM expression level was less in tumor. In this case, it was suggested that elevation in plasma AM level might be a factor associated with normotensive blood pressure; however, adrenal pheochromocytoma was not a major source of circulating AM. To our knowledge, this is the first case of pheochromocytoma in patient with HD associated with AM in the literature.