Kazuhiro Takai

Validity of Short-term Examination for Antipromoters of Bladder Carcinogenesis

Various compounds were screened for antipromoter activity in bladder carcinogenesis in rats with a view to using them clinically to inhibit postoperative intravesical ectopic tumor growth of superficial papillary bladder cancer. Their inhibitions of the effect of sodium saccharin in maintaining increased agglutinability of bladder cells by concanavalin A were examined in 4‐week tests. The compounds found to inhibit the effect of saccharin were α‐tocopherol, ascorbic acid, aspirin, all‐trans aromatic retinoid, α‐difluoromethylornithine, sodium cyanate and p, p′‐diaminodiphenylmethane. Considering the toxicities of some of these chemicals, ascorbic acid and α‐difluoromethylornithine were concluded to be the most promising for future clinical trials.

Thymic enlargement following treatment for a metastatic germ cell tumor: a case report.

We describe a patient with metastatic testicular carcinoma in whom an anterior mediastinal mass developed 8 months after complete remission following chemotherapy and surgery. The mass was excised and pathological examination showed benign thymic hyperplasia. An anterior mediastinal mass encountered after successful chemotherapy does not always imply recurrence or relapse of malignant disease. The possibility of a benign etiology must be considered to prevent inappropriate treatment.

Analyses of avidin-biotin complexes with lectins of membrane glycoproteins in the urinary bladder of rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine.

The bladder epithelium was examined by staining with avidin-biotin complexes with lectins to determine the early membrane changes during bladder carcinogenesis in rats treated with N-butyl-N-(4-hydroxybutyl)-nitrosamine (BHBN). Concanavalia ensiformis (Con A), Triticum vulgaris (WGA), Ricinus communis (RCA) and Arachis hypogaea (PNA) were used as probes. The cellular distributions of lectin particles were distinguished into membranous and cytoplasmic patterns. Normal bladder cells stained very slightly and showed a spotty membranous pattern. After treatment of rats with BHBN for two or three weeks, staining became stronger and its pattern changed from a membranous to a cytoplasmic type. The staining of bladder cancer cells induced by BHBN varied from area to area and with different lectins. These data indicated that changes in carbohydrates occur in the bladder cell membrane during the early phase of carcinogenesis.

Multiple pulmonary metastasis of prostatic carcinoma with little or no bone or lymph node metastasis. Report of two cases and review of the literature.

We describe 2 cases of prostatic carcinoma with pulmonary metastasis. In the first case there was no lymph node or bone metastasis, and in the second case there was only one bony metastatic lesion. Presentation, etiology and management are discussed.

Sequential changes in the prostate of rats treated with chlormadinone acetate, testosterone and N-nitroso-N-methylurea.

An attempt was made to induce prostatic adenocarcinoma in rats. Temporary chemical castration of F344 rats was achieved by administration of diet containing 0.05% chlormadinone acetate (CMA) for three weeks. The prostate was then stimulated by three consecutive daily intramuscular injections of testosterone propionate (100 mg./kg.). On the day after the last testosterone injection, N-nitroso-N-methylurea (NMU) (50 mg./kg.) was injected intravenously. Animals were sacrificed 10 days and 4, 20, 40 and 60 weeks after NMU treatment. Well-differentiated adenocarcinomas were obtained in three of fifty-four animals (5.6%) by this treatment and a high incidence of simple hyperplasia (88%) and atypical hyperplasia (19%) was also observed at 60 weeks. More studies are necessary to develop a protocol resulting in more rapid induction of prostatic adenocarcinomas at higher incidence.

Trial to Induce Prostatic Cancer in ACI/Seg Rats Treated with a Combination of 3,2′-Dimethyl-4-aminobiphenyl and Ethinyl Estradiol

In an attempt to induce prostatic adenocarcinoma at higher incidence in a shorter period, we administered diet containing 0.75 ppm of ethinyl estradiol (EE) for three weeks to ACI/Seg rats, which are predisposed to develop a high incidence of microscopic adenocarcinoma of the prostate at higher age. Then, feeding was changed to basal diet and a single subcutaneous injection of 50 mg/kg body weight of 3,2′‐dimethyl‐4‐aminobiphenyl (DMAB) was given two days after the change. We repeated this schedule 10 times. The rats were killed in week 60 of the experiment and subjected to routine autopsy. The average body weight of rats in group 1 given EE and DMAB was lower than that of control rats in group 2. The incidence of adenocarcinoma was not significantly different in the two groups, i.e. 6/74 (8.1%) in group 1 and 2/54 (3.7%) in group 2. The lesions were all microscopic. The incidence of atypical hyperplasia was significantly higher in group 1 at 17 of 74 rats (23.0%) whereas in group 2, it was only 2 of 54 rats (3.7%). Simple hyperplasia was also observed in 25 of 74 rats (33.8%) in group 1, which was significantly higher than that in group 2, where six of 54 rats (11.1%) had this lesion. The reduced growth of animals due to treatments with EE and DMAB probably suppressed the development of prostate cancer in this experiment. Further studies are needed to develop an appropriate model to induce prostate carcinoma at higher incidence in a shorter period.

Relationship Between Papillary and Nodular Transitional Cell Carcinoma in the Human Urinary Bladder

A total of 186 cystectomized specimens were examined by step-sectioning to determine the relation between papillary and nodular transitional cell carcinomas of the urinary bladder. Tumors were classified as papillary (PC), nodular (NC), and carcinoma in situ (CIS) according to their gross and microscopic configurations. These cases, grouped as simple combinations of PC, NC, and CIS, namely, PC, PC + CIS, PC + NC, PC + NC + CIS, NC, NC + CIS, and CIS, were analyzed with respect to (a) the time from the initial symptom to cystectomy, (b) the treatment before cystectomy, (c) the grade, (d) the stage of tumors, (e) the multiplicity of tumors, (f) the presence of papillary structures inside or on the surface of nodular carcinoma, and (g) data on survival after cystectomy. Of the tumors, 17 were classified as CIS and 80 as PC and PC + CIS. Studies on 57 cases suggested an early change from PC to a mixture of PC and NC through papillonodular carcinoma during development, whereas 6 showed late development of NC during repeated recurrence of PC. These courses indicate that some cases of NC developed from PC. On the other hand, 26 cases exhibited direct progression from CIS to NC. Thus nodular invasive carcinomas may develop in two ways: by emergence of a more anaplastic cell population within a preexisting low grade papillary carcinoma; and by de novo development of an invasive nodular carcinoma directly from CIS.

[A case of proliferative chronic cystitis, progressing to obstructive nephropathy, treated by total cystectomy and enterocystoplasty].

A 52 year-old man, being pointed out as with microscopic hematuria and suspected of carcinoma of the urinary bladder at another institution, visited this hospital for further examination. DIP demonstrated an irregular right lateral wall of the urinary bladder. CT of the pelvic cavity revealed a protrusive mass lesion inside the urinary bladder. Cystoscopy proved a circular, edematous and irregular mass lesion around the urinary bladder neck. The pathological examination of TUR specimens showed a proliferative chronic cystitis. However, after about half a year, there was a recurrence of mass lesions in the urinary bladder. Moreover, right non-functional kidney and left hydronephrosis were observed. For preserving renal function, total cystoprostatectomy was performed. Nerve sparing technique for sexual function, and total bladder replacement using a detubularized sigmoid colon to obviate the need for a stoma were adopted. Postoperative course was uneventful and the function of both kidneys was recovered. Normal urination from the urethra and sexual function are both preserved. Pathological examination of the cystectomized specimen confirmed only proliferative cystitis with extensive deep ulceration and thick connective tissues. A rare case in which obstructive nephropathy was caused by proliferative cystitis is reported and discussed.

Treatment of a Case of Asynchronous Bilateral Renal Cell Carcinomas with Inferior Vena Caval Thrombus and Hepatic Metastases

A 56-year-old man underwent a right radical nephrectomy with removal of a vena caval thrombus and resection of hepatic metastases for right renal cell carcinoma. Twenty-one months after the first operation, a left renal cell carcinoma was detected which was treated with left radical nephrectomy and followed by hemodialysis. The patient then enjoyed an active life for 14 months but died 18 months after his second operation due to lung metastasis. Bilateral radical nephrectomy and hepatic resection may be justified since there is no strongly effective adjuvant therapy for such advanced cases.