Colocalization of neuropilin-1 and Flk-1 in retinal neovascularization in a mouse model of retinopathy.

PURPOSE: To investigate the mechanisms of the development of retinal neovascularization, the localizations of vascular endothelial (VEGF) receptors Flk-1 and neuropilin (NP)-1 mRNAs were examined. METHODS: The model of retinopathy of prematurity (ROP) was produced by ischemia-induced ocular neovascularization, by exposing postnatal day-7 mice to 75% oxygen for 5 days and then returning them to room air for 5 days. Retinal neovascularization was visualized by injection of fluorescein-dextran. Expression of Flk-1 and NP-1 mRNAs were examined by in situ hybridization with flatmount and serial sections of the retina. The localization of NP-1 was also confirmed by immunohistochemistry. Blood vessel patterns were characterized by immunohistochemical localization of von Willebrand factor (vWF). RESULTS: Flatmount in situ hybridization showed intense expression of NP-1 and Flk-1 mRNAs colocalized in the area of neovascularization. In situ hybridization of serial sections of the retina revealed that expression of Flk-1 and NP-1 was restricted to neovascularized vessels of the retina from ROP mice. CONCLUSIONS: The restricted expression of Flk-1 and NP-1 on neovascularized vessels suggests that these molecules may play important roles in retinal neovascularization. This is the first report of the colocalization of NP-1 and Flk-1 on neovascularized vessels of the retina from ROP mice.

CA19-9-producing transitional cell carcinoma of the renal pelvis: a case report.

We report a case of CA19-9-producing transitional cell carcinoma of the renal pelvis. A 59-year-old male patient with left hydronephrosis was referred to us from a local physician. Retrograde pyelogram revealed irregular filling defects involving calices, pelvis and proximal ureter. The serum CA19-9 level was elevated. Under the diagnosis of renal pelvic tumor, we performed radical left nephroureterectomy. The tumor was histologically diagnosed as transitional cell carcinoma. The tumor cells showed positive immunostaining for CA19-9. The serum CA19-9 level was normalized after the operation. To our knowledge, this is the 28th case of a CA19-9-producing tumor in the Japanese literature.

[Long-term results and quality of life of hemi-Kock orthotopic ileal neobladder after radical cystectomy].

We analyzed the long-term results and the quality of life in patients who received orthotopic lower urinary tract reconstruction using the Kock ileal neobladder. Between July 1990 and October 1993, 37 consecutive patients including 2 females received orthotopic hemi-Kock neobladder after radical cystectomy. In these patients, we analyzed the urinary continence, complications and urethral recurrence, and performed a questionnaire survey by mail. Good continence all day had been achieved in 71% of the patients 4 years after surgery. The rate of the pouch-related complications requiring reoperation was 27%. There was no urethral recurrence. Compared with preoperative conditions, 42% were not satisfied with urination. In these dissatisfied patients, the need to use pads in the daytime, sensation of residual urine and weak urine stream were significantly more frequent than in satisfied patients. In summary, the rate of complications was higher than that of other methods. However, the Kock orthotopic ileal neobladder is a stable procedure providing good function over the long-term.

[Dramatic improvement with immunoabsorption therapy in a 7-year-old girl with severe Guillain-Barré syndrome after unsuccessful gammaglobulin therapy].

We report a 7-year-old girl with severe Guillain-Barré syndrome (GBS) who showed dramatic improvement after immunoabsorption therapy. She had progressive muscle weakness with resultant respiratory failure. On the 7th day of the illness, she was nearly quadriplegic and dependent on mechanical ventilation. In addition, she had autonomic manifestations, areflexia, abolished or delayed peripheral nerve conduction, and increased CSF protein. Administration of a high dose of gammaglobulin failed to improve the symptoms. Immunoabsorption therapy using a tryptophan column was performed 9 times during 17 days. After 5 times of immunoabsorption therapy, the muscle weakness improved dramatically; she was extubated 16 days after the institution of the therapy and walked without assistance on the 41st day. She regained normal muscle power without any sequelae. The immunoabsorption therapy caused hemolysis and decrease of serum fibrinogen, but no serious complications. The clinical course of this patient suggests the efficacy of immunoabsorption therapy in GBS.

A randomized study of short-versus long-term intravesical epirubicin instillation for superficial bladder cancer. Nagoya University Urological Oncology Group.

OBJECTIVE: A prospective randomized study was undertaken to determine whether prophylactic maintenance instillation of epirubicin following induction treatment is beneficial in patients with superficial bladder cancer. PATIENTS AND METHODS: One hundred and forty-eight patients with resectable superficial bladder cancer (Ta-1, single, multiple, primary or recurrent with, however, no recurrence during the last year) were enrolled in this study. In both arms, epirubicin (40 mg/ml in normal saline) was administered six times within 4 weeks after a transurethral resection of the bladder tumor(s). In arm A, the patients received 11 additional monthly instillations of epirubicin. RESULTS: Of the 148 patients, 138 (93.2%) were eligible and followed for an average of 29.6 months. 93 (67.4%) had a solitary tumor. No significant difference in the recurrence-free curve was observed between the two arms (p = 0.62). The recurrence rate per year was 0.16 in arm A and 0.17 in arm B. Toxicity included vesical irritability in 10 (7.2%) and hematuria in 1 patient. No significant difference in the frequency or degree of toxicity was observed between the two arms. CONCLUSION: These data suggest that maintenance instillation of epirubicin does not reduce superficial bladder cancer recurrence.

Laparoscopic radical nephrectomy: the Nagoya experience.

PURPOSE: We evaluated the efficacy of laparoscopic radical nephrectomy for removing kidneys with small volume renal cell carcinoma. MATERIALS AND METHODS: 25 patients (19 men and 6 women, mean age 59) who had a kidney with small volume renal cell carcinoma (diameter less than 5 cm.), underwent laparoscopic radical nephrectomy. The kidney was dissected laparoscopically together with the adrenal gland, perirenal fatty tissue and Gerota's fascia. In 11 patients, we used the transperitoneal approach and in the remaining 14 we used the retroperitoneal approach, in which a working space is created by finger and balloon dissection. We maneuvered the kidney into the laparoscopy sack, which was then removed through an additional 5 to 6 cm. incision. RESULTS: All 25 kidneys were removed successfully. Mean operation time was 5.3 hours and mean estimated blood loss was 335 ml. There were 5 complications, including a patient who suffered an injury to the duodenum, which was treated by open duodenojejunostomy. Full convalescence occurred at an average 23 days. No metastatic disease, no local recurrence and no seeding at the port sites occurred during the followup of 7 to 49 months (mean, 22 months). CONCLUSIONS: Laparoscopic radical nephrectomy is recommended as a minimally invasive procedure for removing kidneys with small volume renal cell carcinoma.

[A case of malignant lymphoma after renal transplantation].

A case of a primary brain malignant lymphoma after renal transplantation and immunosuppressive therapy is reported. A 41-year-old male patient had been treated with 125 mg/day of azathioprine and 10 mg/day of prednisolone after renal transplantation. He had also been suffering from various infectious diseases. Multiple brain tumors were found and diagnosed as having B-cell, diffuse large cell type malignant lymphoma. In spite of moderate response to irradiation, he died of pneumonia. The anti-Epstein Barr virus antibodies changed from a negative to a positive level after renal transplantation and they increased markedly after brain malignant lymphoma had been found. The number of T- and B-lymphocytes also decreased markedly at that time. So the Epstein-Barr virus was suspected to be the cause of the malignant lymphoma.

[Bilateral synchronous testicular seminomas: a case report and review of the Japanese literature].

A 39-year-old man was referred to our hospital with right testicular swelling. Ultrasonography and magnetic resonance imaging revealed bilateral, synchronous testicular tumors. Bilateral high inguinal orchiectomy was performed. Histological examination revealed anaplastic seminomas. Prophylactic radiation therapy was performed in the para-aortic and pelvic regions postoperatively, and no signs of metastasis have been found during the follow-up period of more than 5 months. Including the present case, 186 cases of bilateral testicular tumors reported in Japan are reviewed.

Immunosuppressive treatment of primary cadaveric renal transplant patients receiving kidneys from non-heart beating donors.

Since November 1982, 276 primary cadaveric kidney transplants have been performed using kidneys from non-heart beating donors. Between November 1982 and December 1986, 49 transplant patients were treated with cyclosporine and steroid immunosuppressive therapy (CSA regimen). Twenty-seven patients were treated with low dose cyclosporine (initial dosage, 4 mg/kg/day), steroid therapy, and a 21-day course of 500 mg/day antilymphocyte globulin (ALG 1 regimen) between January 1987 and December 1987. Seventy-nine patients were treated with low dose cyclosporine (initial dosage, 6 mg/ kg/day), steroid therapy, and a 14-day course of 1,000 mg/day antilymphocyte globulin (ALG 2 regimen) between January 1988 and June 1990, and 85 patients were treated with low dose cyclosporine (initial dosage, 6 mg/ kg/day), steroid therapy, and a 14-day course of 1,000 mg/day antilymphocyte globulin followed by 2 mg/kg/day mizoribine (ALG 3 regimen) between July 1990 and May 1995. Ten patients, who showed hypersensitivity to antilymphocyte globulin therapy, were treated with low dose cyclosporine, steroid therapy, and mizoribine. Finally, 26 patients were treated with FK506 and steroid therapy (FK506 regimen) between June 1990 and February 1992. Graft survival was 78% at 1 year, 69% at 3 years, 63% at 5 years, and 51% at 10 years in the CSA regimen group and 67% at 1 year, 52% at 3 years, and 48% at 5 years in the ALG 1 regimen group. It was 85% at 1 year, 70% at 3 years, and 62% at 5 years in the ALG 2 regimen group and 87% at 1 year and 67% at 3 years in the ALG 3 regimen group. In the FK506 regimen group, graft survival was 92% at 1 year and 80% at 3-5 years. Never-functioning grafts were observed in 3 CSA patients (6%), 1 ALG 1 patient (4%), 3 ALG 2 patients (4%), 3 ALG 3 patients (4%), and 1 FK506 patient (4%). These results indicate that low dose cyclosporine (initial dosage, 6 mg/kg/day), steroid therapy, and a 14 day course of antilymphocyte globulin therapy is beneficial for cadaveric renal transplant patients receiving kidneys from non-heart beating donors; FK506 and steroid therapy might be more effective than cyclosporine based immunosuppressive therapies even in such patients.

[Laparoscopic pelvic lymphadenectomy for localized prostate cancer].

We report the clinical results and efficacy of laparoscopic pelvic lymphadenectomy for localized prostate cancer. This procedure was followed by radical prostatectomy, when metastasis was not found in the frozen section, and by optional treatment, such as transurethral resection (TUR) or castration, other than radical prostatectomy when metastasized nodes were found. We performed transperitoneal laparoscopic lymphadenectomy on 30 patients and extraperitoneal approach on 20 between April, 1992 and September, 1995. The patients were between 52 and 78 years old. Nineteen, patients had stage B1, 17 stage B2 and 14 stage C cancer. Bilateral obturator nodes were dissected. We could not perform laparoscopic lymphadenectomy on two patients because of adhesion. The average operation time and blood loss were 166 minutes and 151 ml, respectively, in the transperitoneal group, while 142 minutes and 126 ml in the extraperitoneal group. The average number of removed nodes was 12 in the transperitoneal group and 10 in the extraperitoneal group. The extraperitoneal approach is a safer and useful procedure. Nodal metastasis were found in 12 patients by frozen section. Additional positive nodes were found in 7 patients by a further study. Two were not harvested laparoscopically and 5 were ascertained only by permanent section. Therefore, the two-staged operation might be preferable. Nodal metastasis was likely to be found in localized prostate cancer patients with clinical stage C, poorly differentiated cancer, or prostatic specific antigen density (PSAD) over 0.5 ng/ml/ml. Laparoscopic pelvic lymphadenectomy might be indicated for these cases.

Laparoscopic nephrectomy via the retroperitoneal approach.

PURPOSE: We evaluated efficacy of the retroperitoneal approach for laparoscopic nephrectomy of kidneys with benign disease. MATERIALS AND METHODS: Eight men and 12 women (mean age 55 years) with severely damaged kidneys underwent laparoscopic retroperitoneal nephrectomy. One patient had a history of multiple open abdominal and gynecological operations. Kidneys were removed laparoscopically from the working space, which was created by finger and balloon dissection, and maintained by carbon dioxide insufflation in the retroperitoneal cavity. RESULTS: All kidneys were removed successfully via this procedure. Mean operative time was 3.3 hours and mean estimated blood loss was 135 ml. One patient experienced bleeding from the injured capsular artery just after removal of the kidney. CONCLUSIONS: The retroperitoneal approach is recommended for laparoscopic nephrectomy.

Laparoscopic adrenalectomy via the retroperitoneal approach: first five cases.

Between February and November 1994, we performed laparoscopic retroperitoneal adrenalectomy in five patients with benign adrenal tumors to confirm the efficacy of this operation. Using digital dissection and a balloon, we created a working space in the retroperitoneal cavity before we dissected the adrenal gland and removed it under laparoscopic observation. The adrenal glands of all five patients were removed without any complications. The mean operative time was 3.4 hours, and the mean estimated blood loss was 148 mL. The average postoperative hospital stay was 10 days, and the average full recovery time was 19 days. We concluded that the retroperitoneal approach is an advantageous and safe procedure in the laparoscopic removal of the adrenal gland with benign tumor.

[Hautmann's ileal neobladder: experience of 37 cases].

Between April 1993 and August 1995, a Hautmann's ileal neobladder was created in 37 men after total cystectomy for bladder cancer. Ureteroileostomy was performed using a submucosal tunnel instead of the Le-Duc Camey procedure. There was no operative mortality and only a few early complications. The mean postoperative follow-up time was 16 months, with a range of 3 to 31 months. Hydronephrosis occurred in 3 patients, being caused by stenosis at the uretero-ileo anastomosis in 2 and by proximal stenosis in 1. Neobladder-ureteral reflux did not occur in any of the patients. Postoperative ileus developed in 3 patients, and one required laparotomy. Stenosis of the urethro-ileal anastomosis developed in 3 patients, who were successfully treated by transurethral incision. Thirty five patients achieved daytime continence, while 2 patients had slight incontinence. Twenty nine patients achieved nighttime continence, and most of the patients awoke 1-4 times to prevent overflow incontinence. The mean maximum flow rate, average flow rate and post-voiding residual urine volume were respectively 15.3 ml/sec, 5.5 ml/sec and 81 ml at 6 months postoperatively, and 14.9 ml/sec, 5.4 ml/sec and 76 ml at 12 months. Four patients with more than 100 ml of residual urine required sterile intermittent catheterization 2-4 times a day. Urethral recurrence was detected in 2 patients. One was treated with transurethral resection and cisplatinum-based systemic chemotherapy, and the other required urethrectomy and urinary diversion using a new continent efferent limb.