Our activities
Dpt. Urol., Hamamatsu Univ. Sch. Med.
Adrenal tumor （cf. Endoscopy）
Nephrotoxic mechanism of drugs
Antibiotic nephrotoxicity
Cyclosporin-A induced nephropathy
Kidney transplantation
Urinary stone
Treatment of urolithiasis （cf. Endoscopy）
Colic is provoked by weather
In vitro microlith formation by MDCK cells
Urinary tract infection
Urinary dysfunctions
Benign prostatic hypertrophy （cf. Endoscopy）
Oncology
Kidney cancer
Futraful for kidney cancer
Interferon and other immunotherapy
Bladder cancer
Various efforts to improve the results of TUR-Bt
Prostate cancer
Early prostate cancer
Chemotherapy on prostate cancer
Ultrasonography
Endoscopic surgery
In Japan, adrenalectomy was developed by the famous Prof. Ichikawa at the Tokyo University. It is the reason why Japanese urologists are acustomed with adrenalectomy. We have treated many patients with adrenal tumor. ASO and IKEDA, the professor of anesthesiology, found that shorter-acting α-blockers, Ca channel-blockers, and ATP were useful to control blood pressure during surgery without altering secretion of catecholamine from pheochromocytoma. SUZUKI started the laparoscopic adrenalectomy in 1992 and accumulated a large series of laparoscopic adrenalectomy.
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Antibiotic nephrotoxicity
Among antimicrobial antibiotics, aminoglycosides are well-known to cause nephropathy. To know and compare the characteristics of toxicity, FUJITA tried to localize the antibiotics in the kidney cell fractions. Aminoglycosides had the affinity to micosomes, and then to lysosomes. The first, reversible step of the binding to lysosomes occurred in vitro. This reversible binding occured also in vivo. In vivo, animals accumulated a large volume of aminoglycosides in lysosomes at the first step. The second step of accumulation was irreversible and it was compatible with the myelin body formation on EM observation.
Tetracycline had a high affinity to mitochondria. However, the binding was reversible and decreased rapidly with the excretion of drug. The affinity of antibiotics to such larger organella as mitochondria and lysosomes were correlated well with the nephrotoxic characteristics. Although the antibiotics of cephem group was not so nephrotoxic, cephrloridine, the first derivative clincally used, showed the affinity and was nephrotoxic.
FUJITA's quantitative subcelllular fraction method was able to compare these nephrotoxic characteristics of various drugs, as well as the preventive effects of simultaneous drugs and procedures, or administerating route of the antibiotics. For example, intravenous use of aminoglycosides was prohibited because it was considered to be dangerous. He showed that the intravenous aminoglycosides did not increase the toxicity when compared with the intramuscular route.
FUJITA also used urinary enzymes as the index of nephrotoxicity. Elderly person were vulnerable to aminoglycosides. Aminoglycosides and cisplatinum showed different response patterns and suggested the different mechanism of the drugs in their nephrotoxic effects.
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Cyclosporin-A induced nephropathy
Cycrosporin A(CYA) is a miracle drug to improve the kidney graft survival. But shortly after its clinical use, the nephrotoxic effect was known to develop. ISHIKAWA extensively studied this problem using mice and rats. Renal blood flow was not decreased at the level of interlobular artery; however, renal cortical blood flow, measured by the hydrogen gas clearance method, was decreased. Glomerular afferent arterioles were considered to be constricted by CYA, probably via endothelin(ET). The renin granules in the JG cells were increased, and serum renin and aldosterone were inconsistent ( increased or normal, or sometimes decreased ). These findings suggested the inhibiting effect of ET on the renin release from the JG cells, and it is the mechanism to establish the vasoconstriction. He confirmed the preventive effect of calcium channel blockers, α-adrenoreceptor blockers and ET receptor blockers against the nephrotoxic effect of CYA.
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In 1977, when our hospital opened, kidney transplantation had not been performed here in Shizuoka Prefecture. Therefore, it became one of the main projects of our department. Now we have the experience of over 200 transplantations and the graft survival rate is excellent.
TAJIMA applied lymphocytaphresis for the immunosuppression of patients receiving kidney graft. He wisely performed lymphocytapheresis at the time of hemodialysis by introducing a part of circulating blood from the dialysis circuit. The pheresis was beneficial as the pretransplantation treatment for living donor transplantation, and also as the treatment of acute rejection.
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Urinary stone is a very popular disease. Upper urinary tract stone is prevalent in Japan, as is the rule in the European countries. The cause of urinary stone is still not known, expect the special stones caused from hyperuricemia, hyperparathyroidism, and cystinuria.
ICHIYAMA, professor of the 1st biochemistry, is famous for his study on oxalate metabolism. He was the first in Japan to identify the abnormality of APT/AGT gene in a patient with primary hyperoxaluria type 1. MIZUNO studied the targeting mechanism of APT/AGT by transfecting the modulated genes.
The treatment modality of urinary stone has changed. FUJITA and SUZUKI, independently experienced a large series of ESWL before they moved to this university. OHTA was also famous as a skillful urologist to success transurethral lithotripsy in difficult renal pelvic and ureteric stones. MUGIYA is now taking place of him.
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Colic is provoked by weather
Patients with urinary stone colic come into the outpatient clinic one after another at a certain climate condition. FUJITA was interested with this phenomenon and analysed the influences of weather at Saku area, and at the center of Tokyo. Various factors, such as temperature, air pressure, window, humidity and rain fall, were studied. Low and falling air pressure provoked the colics. Stone formation increased in hot seasons and therefore difficult to analyse the effects of temperature on the colic. However, high and rising temperature provoked the colic. Falling temperature at the cold season was also seemed to increase the colics. These climate changes may influence the sympathetic nerve activity.
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Microlith formation by MDCK cells
NAITOH, a pathologist in our univesity ( now the associate professor ), found stone-like clusters in a well which had been left for more than a month with alive MDCK cells in it: a cell line derived from canine renal tubular cell. It might give us the clue to the genesis of urolithiasis.
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Urinary tract infection (UTI) is very difficult to eradicate when the patient has an indwelling catheter. UTI after TUR-P is a big problem because the indwelling catheter is inevitable after surgery. FUJITA studied this problem from various aspects; the pharmacokinetics of antimicrobials especially their penetration into the prostate tissue, clinical risk factors to develop post-TUR UTI, and tactics to prevent it. Interestingly, he demonstrated that post-TUR UTIs increased in hot summer seasons. He was the first to advocate that oral antimicrobial, instead of intravenous infusion, is enough to prevent post-TUR UTI.
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KAWABE previously studied renin-aldosterone system at the Tokyo Univeristy. His interest moved from hypertension to urinary dysfunction through the study of α-blockers. He studied the distribution and specificity of α-adrenoceptors in the prostate. He also made co-operative studies on the clinical efficacy of various α-adrenoceptor antagonists.
KAGEYAMA made various studies under KAWABE. His method to moniter the collagen injection with ultrasonography was a good idea to perform the procedure safely. He is now trying to establish an experimental method to access bladder muscle activities using intracellular Ca++ concnetration as the index.
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Benign prostatic hypertrophy(BPH) is a popular disease among elderly men. Transurethral resection of the prostate(TUR-P) is well-known to be the most difficult technique to learn for urologists. Based on the experience of near 3,000 TURs, FUJITA published a textbook on TUR-P in 1986. The Japanease version included many valuable suggestions for urologists. Therefore, the Chinese, Spanish and English versions, as well as the second Japanease edition were published.
Recently, various treatment modalities have been developed to replace the difficult technique of TUR-P. We have tried these techniques but have not found an ideal one. The search for a more ideal treatment is still going on. Please see the chaptor of urinary dysturbances.
KURITA tried an extensive ultrasonographic study on BPH. His main concern was the relation between the serum prostate specific antigen(PSA) and transition zone hyperplasia because it became possible to distinguish the peripheral and transition zones by ultrasonography. Interestingly, PSA level depends on the transition zone, not on the peripheral zone. BPH had been believed as the result of the glandular hyperplasia. However, the role of α1 adrenaline receptor is recently stressed and now the main mechanism is considered to be the increase of α1 receptors in the extraglandular tissue. KURITA found that gland-hyperplasia type BPH responded well to hormone therapy, and non-glandular hyperplasia type BPH responded well to α1 blocker and also, to hyperthermia therapy.
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Renal cancer is notorious because it is not refractory to various drugs. Among the drugs, tegaful and related compounds are fairly effective. In the other hand, sometimes renal cancer disappeared spontaneously. Probable immunologic response was suggested, and interferon was developed as a drug to treat renal cancer.
As we have no effective treating modalities except surgery, prognostic factors of patients themselves are very important. MASUDA, H. analysed the prognostic factors of patients with renal cancer.
HIRANO is trying chemosensitivity test. His aim is to select the most proper anticancer drugs for each patient based on the result of the sensitivity test. He found that some of the renal cancers are sensitive to a certain drug.
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FUJITA, based on his hypothesis that most of the post-TUR recurrences arise from the dissemination of monoclonal bladder cancer cells, made various efforts to decrease the recurrence. The pre-TUR local injection of OK-432 to provocate active immune reaction, and also the intravesical instillation of anticancer agents immediately after TUR to disturbing the possible dissemination of cancer cells, were the methods he tried. He, through the trials, realised that the submucosal injection of nonelectrolyte solution facilitates the complete resection of cancer together with surrounding precancerous lesions, and also found that the injection helps to avoid dangerous perforation which sometimes happens by electrostimulating the obturator nerve.
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Prostate cancer is the most common cancer in men and the second leading cause of male cancer deaths in the United States. It is increasing also in Japan. Because the incidence of subclinical prostate cancer among Japanese is almost same with that of Americans, the incidence of clinical prostate cancer among Japanese will increase. FUJITA compared the rate of incidental prostate cancer among patients underwent TUR-P with that in China (Beijing), and found the rate to be almost the same.
FUJITA was the first urologist in Japan who advocated to use cytotoxic drugs for the treatment of prostate cancer(1976). Although we have no satisfactory drug at now, chemotherapy is one of the most important strategies for patients with prostate cancer. It is especially true with poorly differentiated cancer.
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USHIYAMA is specialised in the ultrasonographic diagnosis. He is famous for his accuracy to identify small parathyroid adenoma by ultrasonography. Ultrasonography is also useful at the bedside to differentiate the genesis of renal failure after renal transplantation.
KURITA, by identifying the transition zone and peripheral zone of prostate, improved the diagnosis of benign prostate hypertrophy(BPH） and cancer.
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Bladder, prostate and urethra
FUJITA experienced many transurethral resections. He published an exellent textbook on
TUR-P, made varous advances in TUR-Bt, and develped internal urethrotomy with a newly developed endoscope.
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Upper urinary tract
ASO reported the first ureteral fiberscope in the world. The Olympus Co., Tokyo, has developed useful fiberscopes and now it is possible to perform various surgical procedures through the transurethral route.
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Laparoscopic surgery
SUZUKI tryed laparoscopic surgery on various lesions. Adrenal is one of the most suitable organs to be removed by laparoscopic surgery.
SUZUKI also dveloped laparoscopy-assisted surgery without gas insufflation. It is a very useful technique advisable for a variety of retroperitoneal and intraperitoneal surgeries.
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