Nobutaka Ohta

Dendritic cell immunotherapy for patients with metastatic renal cell carcinoma: University of Tokyo experience

Background : Dendritic cells (DC) are the most potent antigen‐presenting cells and induce host antitumor immunity through the T‐cell response. A clinical study of immunotherapy using cultured DC loaded with tumor antigen, for patients with metastatic renal cell carcinoma (RCC) was performed.

Treatment of staghorn calculi by fiberoptic transurethral nephrolithotripsy.

We treated 34 patients with staghorn calculi by fiberoptic transurethral nephrolithotripsy with a flexible nephroureteroscope and an electrohydraulic lithotriptor. Of the 34 patients 30 (88.2%) were treated successfully. There were 17 patients each with complete and partial staghorn calculi. There was no difference in the success ratio and the rate of residual fragments between the 2 groups. However, post-procedural fever, sepsis and extrapelvic extravasation were observed more frequently in patients with complete than with partial staghorn calculi. Countermeasures to avoid complications must be developed in the future. However, we believe that fiberoptic transurethral nephrolithotripsy is a safe and effective treatment for staghorn calculi. This procedure also should be recommended, as well as the combination of percutaneous nephrolithotomy and extracorporeal shock wave lithotripsy.

Bredinin treatment in clinical kidney allografting

Bredinin, a new nucleoside antibiotic isolated from Eupenicillium brefeldianum, and steroids were used as immunosuppressive agents in 31 renal transplant patients; 17 of them received grafts from living-related donors and 14 from cadavers. The one-year graft survival rates were 100% in renal recipients from living donors and 69.2% in cadaver kidney recipients. There was no serious complication from the use of these immunosuppressive agents.

Effects of intracavernous administration of adrenomedullin on erectile function in rats

We have reported that adrenomedullin (AM)-induced vasodilation is at least in part nitric oxide (NO)-cGMP-dependent in the rat. Although it is well known that NO is much involved in the erectile function, it is controversial as to whether AM influences the erectile function. Thus, we examined the effects of AM on intracavernous pressure (ICP) during penile erection. The left carotid artery of rats was cannulated to monitor of mean arterial pressure (MAP). Bipolar electrodes were positioned on the cavernous nerve. The right cavernous body was cannulated with a needle connected to a pressure transducer to monitor ICP. Electrical stimulation (ES) increased ICP in a voltage-dependent manner. Elevation of ICP continued during ES. The intracavernous injection of 0.5 nmol AM significantly potentiated ES-induced increases in both maximal developed ICP/MAP and area under the curve (ICP trace; AUC). Since AM slightly lowered MAP, ICP was normalized by MAP. i.v. administration of N(omega)-nitro-L-arginine, a NO synthase inhibitor, markedly decreased AM/ES-induced ICP elevation. However, in the presence of E-4021, a cGMP-specific phosphodiesterase inhibitor, AM further increased both ICP/MAP and AUC. These results suggest that a NO-cGMP pathway is involved in the regulation of AM-induced rat cavernous vasorelaxation.

Prolonged renal parenchymal retention of 99mTc mercaptoacetyltriglycine after nephron-sparing surgery

ObjectiveNephron-sparing surgery is a treatment in which a part of a diseased kidney is resected and some parenchyma of the kidney is spared. Impairment of spared renal parenchyma after the surgery may cause prolonged prarenchymal retention in renal scintigraphy with 99mTc mercaptoacetyltriglycine (99mTc-MAG3). The aim of this study was to determine whether or not parenchymal retention of 99mTc-MAG3 is prolonged after nephronsparing surgery. MethodsTwenty-two patients underwent a total of 29 99mTc-MAG3 studies within 1 year after nephron-sparing surgery. In 17 patients (23 examinations) who had bilateral kidneys, the presence of diffuse prolongation of parenchymal retention was determined for the operated kidney. In all patients, the presence of regional prolongation around the surgical margin was assessed. ResultsDiffuse prolongation was observed in four of 10 examinations performed within 1 month after surgery and in none of 13 examinations performed later than 1 month after surgery. Regional prolongation was shown in 10 of 14 examinations performed within 1 month after surgery and in three of 15 examinations performed later than 1 month after surgery. In five patients who were studied both prior to and later than 1 month after surgery, regional prolongation was noted on the first study. On the second study, regional prolongation was improved and initial renal uptake around the surgical margin was intensified. ConclusionsRenal parenchymal retention of 99mTc-MAG3 is frequently prolonged in the early period after nephron-sparing surgery. Renal scintigraphy with 99mTc-MAG3 may aid in characterizing acute renal damage after nephron-sparing surgery.

EMP combination chemotherapy and low-dose monotherapy in advanced prostate cancer

Many chemotherapeuric regimens combined with estramustine phosphate (EMP) have been elaborated for the treatment of hormone-refractory prostate cancer over 30 years. However, older EMP-based combination chemotherapies with vinblastine, vinorelbine, doxorubicin or cyclophosphamide showed relatively low PSA response rate (25–58%) accompanied with high toxicities. On the other hand, newly developed EMP-based combination regimens with etoposide, pacitaxel, carboplatin or docetaxel demonstrated promising PSA response rate (43–77%) with moderate to severe toxicity in the rate of thromboembolic event (5–18%) and of neutropenia (9–41%). Treatment-related death was less in the latter combination group (5/615, 0.8%) than that in the former group (3/234, 1.3%). Of note, in the docetaxel combination with EMP, PSA response rate is as high as 77% with high rate (41%) of neutropenia but no treatment-related death was observed. Docetaxel combination with EMP seems to be the best regimen, though not completely justified by randomized trials, to be selected in the modern era, which will be followed by paclitaxel, carboplatin and EMP combination with PSA response rate of 71%. In addition, an interim report in 83 patients was presented. They were not consecutively enrolled but were treated on low-dose EMP monotherapy for previously untreated advanced prostate cancer in Department of Urology of Tokyo University and our 21 affiliated hospitals. Overall PSA response rate was as high as 93.4% out of 76 assessable patients. However, overall toxicity rate was abnormally high (39.5%) with drug discontinuation rate of 32.1%. The reason of low drug compliance may be attributed to gastrointestinal symptoms. To overcome the low drug compliance, appropriate patients for EMP administration should be selected by using gene analysis on the basis of sophisticated tailor-made medicine.

Tiny nodule in the testicle: Case report of a sertoli cell tumor

Abstract Sex cord‐stromal tumors of the testis are rare. We report on a small Sertoli cell tumor in the testicle. According to published reports, a nodular lesion on the testicle has a variety of differential diagnoses. Preoperatively, it is very difficult to differentiate between a tumorous lesion and an inflammatory change. When a tiny nodule in the testicle is encountered, we propose limited, testicular‐sparing surgery according to the frozen section diagnosis.

Interferon-related mental deterioration after craniotomy for removal of metastatic renal cancer

Abstract  Interferon‐related severe adverse events on the central nervous system are relatively rare, because interferon‐α (INF‐α) can not cross an intact blood–brain barrier. We experienced remarkable mental deterioration caused by INF‐α administration in a 43‐year‐old man with renal cell carcinoma after surgical removal of a metastatic brain tumor. We detected a high concentration of INF‐α in a cerebrospinal fluid sample, which was comparable to that in the serum at 24 h after the administration of INF‐α; 5 × 106 IU i.m., suggesting that the blood–brain barrier was damaged somehow by the craniotomy. The mental deterioration improved shortly after discontinuation of the INF‐α administration.

Results of the treatment of prostatic cancer

Two hundred and twenty patients with prostatic cancer were treated in our clinic during the past ten years between April, 1977 and March, 1987. The age distribution was from 45 to 91 years old and more than half of patients were in seventies. Stages A, B, C and D were 3.5%, 19.7%, 21.2% and 55.6%, respectively. Hormonal therapy was given in 175 cases (79.5%) as an initial treatment. The first therapy showed effectiveness in 181 (83.8%) of 216 cases; in 153 (87.4%) of 175 cases treated by hormonal therapy. Reactivation after the initial treatment was observed in 59 (32.6%) of 181 cases; in 48 (31.4%) of 153 cases treated by hormonal therapy. The interval between the start of treatment and reactivation for the stage D was significantly shorter than that for the other stages. Elevation of serum alkaline-phosphatase levels, accelerated erythrocyte sedimentation rate and hydronephrosis were significant risk factors for reactivation. Of the 220 cases, 51 (23.2%) died of advanced cancer. The overall 5-year survival rate was 41.2%. High grade and high stage were significantly related to the poor prognosis. In our studies, as hormonal therapy, maintenance on 100 mg of diethylstilbestrol diphosphate daily was found effective for the treatment of prostatic cancer.

Treatment of 255 patients with bladder tumors

During about 10 years from November, 1977 to March, 1987, two hundreds and fifty-five patients with bladder tumors were treated at the Department of Urology, Hamamatsu University School of Medicine and the affiliated hospitals. There were 198 males and 57 females with the highest age incidence in the seventies. Histologically, 242, 11 and 2 tumors were of transitional cell, squamous cell and adenocarcinoma, respectively. Of the 242 transitional cell carcinomas, 7 were Tis; 43 Ta, 111 T1, 33 T2, 19 T3, 5 T4, 14 M+ (with metastatic lesion), and 10 TX. As to grading, 6 was G0; 66 G1, 100 G2, 64 G3, and 6 GX. Staging was correlated with grading. The 5-year survival rates (Kaplan-Meiers method) were 64% in patients with transitional cell carcinoma; 58% in those with squamous cell carcinoma. In patients with transitional cell carcinoma, the 5-year survival rates were 100% for G0, 73% for G1, 73% for G2 and 40% for G3. As to staging, the 5-year survival rates were 67%, 81%, 81%, 35%, 41%, 40% and 12% in patients with stage of Tis, Ta, T1, T2, T3, T4 and M+, respectively. As to the initial treatment, the 5-year survival rates after TUR (137 cases), partial cystectomy (4 cases) and total cystectomy (56 cases) were 81%, 36% and 61%, respectively. The rate of intravesical recurrence after TUR was evaluated with the cumulative non-recurrence rate calculated by Kaplan-Meiers method.(ABSTRACT TRUNCATED AT 250 WORDS)