Effects of alpha-difluoromethylornithine on initiation and promotion of urinary bladder carcinogenesis in a heterotopically transplanted rat urinary bladder.

We previously demonstrated that repeated intravesical instillation of DFMO, an irreversible inhibitor of ornithine decarboxylase, inhibits (or retards) urinary bladder carcinogenesis in rats. The present investigation was conducted to determine if high intraluminal concentration of DFMO alters initiation by MNU and to determine if DFMO inhibition is due to arrest of tumor progression or simply retardation of the tumor development. Results showed that the inhibitory effects demonstrated by DFMO treatment during the early phase of study disappeared as the observation period was extended. Failure to suppress tumor development might be due to failure to control intracellular polyamine levels below the critical level and this failure in turn might be due to the rapid fall of intravesical DFMO concentration following instillation.

Long-term intra-arterial infusion chemotherapy with adriamycin for advanced bladder cancer.

Long-term intra-arterial infusion chemotherapy with Adriamycin (ADM) was performed in cases of bladder cancer prior to total cystectomy. This report describes the effects in 13 cases evaluated more than 3 weeks after infusion of 10 mg ADM once or twice weekly. An oblique skin incision approximately 10 cm long was made in the gluteal region to expose the gluteus maximus muscle. A teflon catheter was then inserted into the gluteal artery and fixed; the distal end was brought out from under the skin in the precordial region. A similar procedure was performed on the contralateral side. The catheter was inserted through the superior and inferior gluteal arteries in five and eight cases, respectively. In the former group, partial response was obtained in two cases, minimal response in two and no response in one, so that primary tumor remission was evident in 40% of the cases. In the latter group, all cases but one attained partial response, i.e., remission was seen in 87.5% of cases treated by inferior gluteal infusion. Skin erosion of the gluteal, perineal, and anal regions and sciatica-like pain were observed in some cases; however neither myocardial effect nor bone marrow suppression, which have been reported as side-effects of ADM, were observed in any of the cases. These results suggest that this therapeutic modality could be effective in the preoperative work-up of candidates for total cystectomy, and also that it could be useful in the treatment of patients in whom total cystectomy is contraindicated.

Prostate specific antigen and acid phosphatase-reactive cells in cystitis cystica and glandularis.

Cystitis cystica (CC) and cystitis glandularis (CG) are common in the urothelium lining the bladder neck and trigone. Because some cases of CG show histologic features strikingly similar to prostatic acini, we hypothesized that some such foci may represent prostatelike metaplasia in the urinary bladder. Forty surgical and autopsy bladder specimens (23 males, 17 females) showing CC or CG were studied using anti-prostate specific antigen and anti-prostate specific acid phosphatase antibodies. Fourteen (35%) of these 40 cases showed positive staining for prostate specific antigen or prostate specific acid phosphatase or both in CC or CG foci. Among these were five female patients. The findings indicate that bladder epithelium is capable of undergoing prostatelike metaplasia and lend support to the hypothesis that the adult bladder stroma closest to the prostate may exert inductive influences on the overlying epithelium to show prostatelike metaplasia.

[Role of lymphangiography in staging carcinoma of the prostate].

Pedal lymphangiography was done on 21 patients with carcinoma of the prostate. The lymphangiograms were positive in 11 cases and negative in 10. Out of 9 patients who underwent lymphadenectomy (5 with positive and 4 with negative findings), operative findings were in agreement with the lymphangiogram in 8 patients (89%). Lymphangiography should be used as the primary procedure in all cases where aggressive therapy is being considered.

[Is renal arteriography necessary for the diagnosis of local staging in renal cell carcinoma?].

The accuracy of computed tomography and arteriography for the diagnosis of local staging of renal cell carcinoma was examined in 39 patients. Their accuracy in predicting perinephric, retroperitoneal lymph node, renal vein and inferior vena caval involvement by the tumor was investigated. The results were correlated with pathologic diagnoses from specimens of nephrectomy and lymphadenectomy in 39 cases. Staging was the same as the findings of computed tomography in 82 per cent of the lesions (27 of 34) and with arteriography in 74 per cent (29 of 39). Compared to arteriography, computed tomography was more accurate in the diagnosis of regional lymph node metastases. Based upon this experience, preoperative arteriography is not routinely recommended for the diagnosis of local staging of renal cell carcinoma.

[A case of gas gangrene in a vesico-vaginal fistula].

A case of gas gangrene is presented. The patient was a 78-year-old woman who was admitted with the diagnosis of vesico-vaginal fistula. Cystography revealed a vesico-intestinal fistula and leakage of contrast medium into the prevesical space, in addition to the vesico-vaginal fistula. Right ureterostomy was performed. Two weeks postoperatively, she complained of severe pain and swelling of her right thigh. The swelling grew rapidly and general condition became worse. A diagnosis of gas gangrene was made 8 days after her first complaint by demonstrating subcutaneous and intramuscular gas formation in X-ray. She died the next day. By the bacteriological examination, this case was non-clostridial gas gangrene.

[Staging pelvic lymphadenectomy for carcinoma of the prostate].

Prospective pathological staging by pelvic lymphadenectomy in 12 patients with clinically localized carcinoma of the prostate disclosed a high incidence (58%) of clinically silent and unsuspected lymph node metastases. The incidence of positive nodes was 0% in patients with clinical stage A disease, 33% in stage B, 100% in stage C disease. Serum acid phosphatase was not a useful staging marker. Excellent correlation existed between histological grade and pathological stage. Gleason's sum was predictive of nodal metastases.

[Surgical aspects of open renal biopsy done by urologic residents at Tsukuba University].

The results of the operative aspects of open renal biopsy performed by urologic residents at our University Hospital during the 18 months from July 1982 to December 1983 were analyzed. Open renal biopsy was performed by 1st to 6th year residents for various renal diseases on 19 male and 12 female patients, i.e., 14 patients from Pediatric Department, 16 patients from Nephrologic Department and 1 patient from Urologic Department. All except for 3 operations were done under the guidance of urologic staff. The length of incisional line ranged from 3 to 7 cm (average 5.1 cm) in pediatric patients, and that of nephrologic and urologic patients ranged from 5 to 15 cm (average 8.7 cm). The average operation time was 89.2 minutes for pediatric patients, although it was 81.1 minutes when 1 patient who had concurrently operated on inguinal herniorrhaphy in addition to open renal biopsy was excluded from the analysis. The average operation time was 122.2 minutes for nephrologic and urologic patients, although it was 112.8 minutes when 1 patient who had lost a large amount of blood was excluded. The average blood loss was 28.2 ml for pediatric patients when 2 patients whose blood loss was recorded as "small quantity" was excluded, but it was 24.5 ml when 1 patient who was concurrently operated on for inguinal herniorrhaphy in addition to open renal biopsy was excluded. The average blood loss during operation was 235.1 ml in nephrologic and urologic patients, but it was 149.95 ml when 1 patient who had lost a great deal of blood (1,598 ml) was excluded.(ABSTRACT TRUNCATED AT 250 WORDS)

[Chemotherapy of advanced seminoma].

Seminoma is one of the most radiosensitive of the solid tumors. Radiotherapy provides a high cure rate for patients with stage I and II seminoma, but the survival rate of the patients with clinically advanced stage III seminoma is only about 30% in the literature. Our case of advanced metastatic seminoma was treated with cisplatinum, vinblastine and bleomycin. Metastatic tumors in the lung disappeared after chemotherapy but recurred shortly. Then regional radiation was given and the tumors disappeared completely. Subsequent prophylactic chemotherapy was given. In view of the observed chemosensitivity of seminoma, it appears that all patients who present initially with metastatic or bulky retroperitoneal disease should be treated with multiple drug chemotherapy including cis-platinum. Residual tumors can be treated by radiation and surgical resection, which will improve the cure rate of advanced metastatic seminoma.

[A case of retroperitoneal liposarcoma].

A 77 year-old woman presented with the chief complaint of a mass in the right upper quadrant. The examination on admission including IVP, echography, Ga scintigraphy, barium enema, CT scan, and angiography revealed that the right kidney and ascending colon were displaced by the mass. Under the diagnosis of retroperitoneal tumor, operation was carried out. Most of the mass was resected with the right kidney. The pathological diagnosis of the resected tumor revealed well differentiated liposarcoma. Convalescence was uneventful and the patient has been well and free from disease for 14 months. Based on our experience and the review of the pertinent literature in English and Japanese, we emphasize the importance of definite surgery and close follow up, as liposarcoma is frequently recurrent.

[A case of lipoma of the spermatic cord].

A case of lipoma of the spermatic cord is presented. The patient is a 68-year-old with the chief complaint of indolent swelling of the left scrotal content which had been noticed about a month ago. A firm elastic and walnut-sized mass with positive transillumination was palpable in the left spermatic cord, but ultrasound sonography demonstrated that it was a solid mass. Though the tumor was punctured with a 18-gauge needle, nothing could be aspirated. The tumor was removed and histologically diagnosed as lipoma originating in the left spermatic cord. Including the present case, 38 Japanese cases of lipoma of the spermatic cord are reviewed.

[Clinical study of urinary cytology: with special reference to bladder cancer].

During the last 66 months, 482 urinary cytologic examinations were performed on 160 inpatients suspected of having genitourinary cancer at our University Hospital. Cytologic diagnosis was done according to the Papanicolaou's classification. The cytologic findings were compared by size, shape, numbers of the tumor and the histologic findings. The positive rate (classes IV and V) was 56.7% (90 patients) in bladder cancer, 22.2% (18 patients) in prostatic cancer, 13.3% (15 patients) in renal cancer and 62.5% (8 patients) in renal pelvic or ureteral cancer. There was no false positive case for benign disease. The positive rate of cytologic examinations for stage A bladder cancer was statistically lower than that for stage B, C and D cancers. There were no statistically significant differences among the stage B, C and D groups. The positive rate in the low grade (grade I and II) bladder cancer was statistically lower than that of high grade (grade III and IV) cancer. In the small tumor less than thumbtip -sized, cytological diagnosis was positive in 40.0%, while in the large tumor larger than this size, the positive rate was 73.3%. The difference between these two groups was statistically significant. The positive rate in the non-recurrent cases of the bladder cancer was 64.5%, while that in the recurrent cancer cases was 39.3%. The difference between these two groups was statistically significant. The positive rate of urinary cytology did not correspond to the shape or number of tumors. It is desirable to perform cytology more than 3 times on the same patient.(ABSTRACT TRUNCATED AT 250 WORDS)

[Postoperative complications and followup in cystectomy].

Clinical studies on postoperative complications and prognosis were done on 27 patients who had undergone cystectomy at our hospital. Thirty one postoperative complications were seen in 16 patients. Early complications which developed within 3 months of operation were more frequent (25 cases). They included pyelonephritis (5 cases), wound infection (4 cases), pulmonary complications (2 cases), cardiovascular complications (2 cases), ileus (2 cases) and delayed ambulance (2 cases) in decreasing order of frequency. Complications related to urinary diversion were observed in 4 out of 6 late complications. Reoperation secondary to surgical complications were done in 6 cases. Four of the 6 reoperations were related to gastrointestinal complications, all of which would be fatal if left untreated. Postoperative followup period ranged from 3 weeks to 49 months with a mean period of 12.8 months. The present status of the patients is as follows: 16 patients alive, 10 patients dead and 1 patient lost to followup. So far we cannot draw a definite conclusion regarding the relationship between surgery and the prognosis of the patients because the followup period is too short in many patients. In our experience: 1) The fewest cancer deaths occurred in patients who had undergone radical surgery; 2) the largest percentage of living patients was seen in the group of patients who had undergone radical cystectomy; and, 3) almost all patients with low stage tumors are living more than 6 months after operation.

[Studies on the urophonography (1)--Basic investigation with the model of lower urinary tract].

The purpose of this study is to ascertain whether the urinary (turbulent) flow really causes the sounds during micturition in humans. For this purpose the artificial bladder and urethra, which were made of silicon rubber (3M Co. Minnesota, U.S.A.), were used. The manometric device was attached to the bladder to measure the intravesical pressure. Outside the bladder neck a prostate like protrusion surrounding the urethra was made. A microphone was attached to this protrusion to detect the sound. A recording system was also adopted. The bladder was filled with 200 ml of sterile eater. By pressurising the artificial bladder at 100 cmH2O, the water passed through the urethra. During this artificial voiding the sound detection was undertaken. At the same time uroflowmetry was also performed. It was demonstrated that sound spikes were recorded whenever water in the artificial bladder passed through the artificial urethra.

[Studies on the urophonography (3)--Clinical investigation on prostatic cancer].

Recently we have developed an entirely new method of sonic detection of lower urinary tract disorders during micturition. This procedure was designated as "urophonography" and its recording as "urophonogram". Sixteen patients with prostatic cancer before and three months after anti-androgenic therapy and ten healthy male volunteers underwent urophonography. The urophonograms were classified into four types. Type 1 was characterized by its diamond shape, while Type 2 was characterized by its random sound spikes. Type 3 was a mixture of Types 1 and 2. Type 4 had few sound spikes. Analysis of these urophonograms also revealed that the frequencies of these urethral sounds belonged to the range from 0.4 to 1.5 KHz. The amplitude (power) of the sounds was in the range of 40-60 dB. Healthy volunteers belonged to Type 4. Prostatic cancer patients belonged to Types 1, 2 and 3 at 18.8, 68.8, nad 12.4%, respectively. After the treatment the percentages of Types 1, 2, 3, and 4 changed to 18.8, 50.0, 0, and 31.2%, respectively. Comparison of uroflowmetric parameters with urophonograms showed that Type 2 patients showed a lesser degree of micturition disturbances, evidenced by these parameters. It was considered that urophonograms were useful as urodynamic investigation.

[Studies on the urophonography (2)--Clinical investigation on normal human subjects and patients with benign prostatic hypertrophy].

Recently we have developed an entirely new method of sonic detection of lower urinary tract disorders during micturition. The detection of these sounds was performed by a data catching and recording system, consisting of a detector, amplifier, and recorder. This procedure was designated as "urophonography" and its recording as "urophonogram". Twenty-five patients with BPH before and three months after suprapubic prostatectomy and 10 healthy male volunteers underwent urophonography. The urophonograms were classified into four types. Type 1 was characterized by its diamond shape, while Type 2 was characterized by its random sound spikes. Type 3 was a mixture of Types 1 and 2. Type 4 had only few sound spikes. Analysis of these urophonograms also revealed that the frequencies of these urethral sounds belonged to the range from 0.4 to 1.5 KHz. The amplitude (power) of the sounds was in the range of 40-60 dB. Healthy volunteers belonged to Type 4. BPH patients belonged to Types 1, 2 and 3 at equal frequency. Comparison of uroflowmetric parameters with urophonograms revealed that Type 3 patients with BPH showed a lesser degree of micturition disturbances, which was consistent with the weight of prostatic tumors surgically resected. Urophonography was undertaken before and after the treatment on these patients. It was clearly shown that the pattern of urophonograms shifted to normal (Type 4). It was considered that urophonograms were useful for urodynamic investigation.

[Studies on the clinical effectiveness of combination therapy with irradiation and chemotherapy for advanced bladder cancer].

The effectiveness of a preoperative combination of chemotherapy and irradiation on advanced bladder cancer was evaluated. The combination therapy group (Arm I) included 21 patients, the preoperative chemotherapy group (Arm II) 14 patients, and a group without preoperative treatment, 35 patients. There were no distinguishing background factors among the three groups. Chemotherapy included vincristine, adriamycin, mitomycin, bleomycin/and 5-FU. A total of 3000 rads was irradiated locally, and the results were promising. The Arm I group was superior to the other two groups in terms of response rate, histological effectiveness and downstaging effects. Also, the 5-year-survival rate for Arm I was much better than in the other groups. There were no great differences in adverse effects between Arm I and II.

[Urogenital cancer].

Treatment of urogenital cancer has made great progress due to early detection by various imaging techniques. Renal cancer is a good example of cancer that has been diagnosed in the earlier stages by the routine imaging methods. BRM therapy of interferons and interleukin II has been proved useful for renal cancer. It has been difficult to diagnose the wall invasion of the bladder cancer. However, ultrasonic imaging has made it possible to detect precisely the invasion into the vesical muscles and adventitia. Also, prostatic acid phosphatase and prostatic specific antigen have become more specific markers for prostatic cancer. Various treatments for this malignancy, including operative surgery, have made progress. The results of chemotherapy for testicular cancer have become fruitful by the use of cisplatin.

[Phase II collaborative study of (2''R)-4'-0-tetrahydropyranyladriamycin (THP) for urological malignancies--Urological Co-operative THP Study Group].

A Phase II clinical trial of a new anthracycline, (2''R)-4'-0-tetrahydropyranyladriamycin (THP), was performed in 137 patients with urological malignancies. Out of them, 111 patients were evaluated for tumor responses and 125 patients were evaluated for adverse effects. In cases of intravenous administration, overall response rate was 18.5% (22.2% for bladder cancer, 30.0% for tumors of the renal pelvis and ureter, and 6.7% for prostatic cancer). In the case of intra-arterial administration, overall response rate was 42.9% (50.0% for bladder cancer). For 50 patients with superficial bladder cancer intravesical chemotherapy with THP was performed. Sixteen patients showed complete disappearance of the tumor, 2 patients showed more than 90% tumor regression and 12 patients showed more than 50% tumor regression, respectively. Overall response rate was 60%. Cardiotoxicity was minimal. Alopecia was noted in a total of 16 patients, but this was minimal. Leukocytopenia was the major adverse effect among patients undergoing systemic THP administration. In conclusion, THP was most effective against transitional cell carcinoma of the urinary tract.