Of 3 kinds of animals with congenital hormone deficiency, i. e., mouse with Snell pituitary dwarfism (dw)in which hypoplasia of the pituitary anterior lobe is seen from embryonal stage and which almost lacks in growth hormone (GH), prolactin (PRL), thyroid stimulating hormone (TSH)and adrenocorticotrophic hormone (ACTH); mouse with little dwarfism lacking only in GH (lit); and mouse with congenital primary hypothyroidism in which the thyroidal gland shows hypoplasia, thyroxine (T4)in blood is not measurable and, conversely, TSH level is abnormally high (hyt), the males of dw/dw and hyt/hyt have been proved to be infertile, but it is little known about lit/lit. After performing early recovery experiment by administering GH+T4 to dw/dw, GH to lit/lit and T4 to hyt/hyt from birth, the testicles of 40-day-old mice were investigated morphologically in the normal control group, non-treated group and treated group in order to clarify the relation between hormones and the sperm-generating potency. The total number of sperm-generating cells, which consist of spermatogonia, spermatocytes, spermatids and sperms, showed remarkable decreases, compared with each control group, and the decrease in total cell number was improved favorably by treatment with hormone. In comparison with the control groups, significant decreases were showed in the spermatid number for the dw/dw group, sperm number for the lit/lit group, and spermatid and sperm numbers for the hyt/hyt group. These results indicate that GH and T4 have a potential effect on sperm-generating function.
Flow cytometric DNA analysis (FCM) of adrenal tumors was studied to evaluate whether FCM will be a useful examination for differentiating between benign and malignant adrenal tumors. 10 specimens of surgically resected (for renal cell carcinoma confined within the middle or lower pole) normal adrenal glands and 20 specimens of surgically resected adrenal tumors were submitted for the study. Hyperplastic adrenal cortex as well as normal adrenal gland showd normal diploid pattern. On the other hand, some of the cortical adenomas showed tetraploid patterns, which has been known to be an index of malignancy in most of the flow cytometric intervention to other solid tumors. Conn adenomas were especially apt to show this tendency, in which as much as 86% showed tetraploid pattern. Proliferation Index (PI) (ratio of S+G2+M cells for the whole population of analized cells) were as much as 9.45±6.97% in normal adrenal cells, whereas it was much higher in cortical adenomas (17.75±8.53%). As a matter of fact, PI of hyperplastic adrenal cortex was within the same range as that of the normal adrenal glands. In pheochromocytomas, aneuploid pattern, which has been believed to be a definite index of malignancy, was shown in 60% of the cases, tetraploid pattern in 20%, and normal diploid pattern in only 20%. As a matter of fact, a case of non functioning cortical adenocarcinoma and a case of malignant pheochromocytoma were judged to show typical aneuploid pattern. Thus, the application of the flow cytometric diagnosis for adrenal tumors was supposed to require some refinement in understanding the significance of aneuploidy or tetraploidy.
The chorioallantoic membarane of chick embryo was used to examine the responses of tumor cell lines and surgically resected specimens to anticancer agents in combination with or without hyperthermia. B16-F10 melanoma, KK-47 cell line derived from a transitional cell carcinoma of the bladder and surgical specimens from urological malignancies were transplanted onto the chorioallantoic membrane of chick embryo 10 days after fertilization. The effects of intravascularlly injected cyclophosphamide, cisplatin, adriamycin, mitomycin C, vincristine and vinblastine, in combination with or without hyperthermia, on the growth of the grafts were investigated. A 15-minute 42.5°C hyperthermia exhibited most favorable anticancer effects in B16-F10 grafts (P<0.01) of all heating conditions tested. A combined use of hyperthermia and cisplatin, cyclophosphamide or adriamycin demonstrated a significantly high tumor regression rate in B16-F10 grafts (P<0.01). In KK-47 grafts, a single use of cyclophosphamide and a combined use of hyperthermia and cyclophosphamede exhibited a highly significant antitumor regression (P<0.05). Surgical specimens from 14 urological malignancies were subjected to this assay. Growth which was adequate for sensitivity test was obtained in 11 of the 14 malignancies. The results obtained suggest that this assay system may be a useful chemohyperthermia sensitivity test.
Ten cases were treated by partial cystectomy for bladder carcinoma (anterior wall 5 cases, dome 1 case, dome to anterior wall 2 cases, lateral wall 2 cases) and these defects were covered with lyophilized human dura (LHD). A few minutes before use, LHD was put into saline for rehydration and, for anastomosis, we used 2 zero plain catgut. In eight cases cardiovascular complications, DM and livercirrhosis were found before operation. The mean operation time±SD was 109±26 minutes, and the indwelling catheter was left in place for 15 to 42 days. In three cases, prolonged urine leak from the wound continued after operation, and in one case temporal VUR was found without clinical significance. No severe urinary tract infection was found in all cases. The inner surface of dura was almost epithelialized after 8 weeks, 8 cases were in good clinical condition but one case was treated by TUR for recurrence of bladder tumor 1 year and 3 months after operation. Our results with LHD as a substitute for the bladder wall have been satisfactory. The main advantage of this technique is that large vesical segmental resection is possible to such an extent as to satisfy Prout's criteria (at least 3cm of apparently normal bladder are available to be excised around the tumor).
We herein report the preliminary but appreciable results of regional transarterial infusion of 2 gravity subtypes of autologous lymphokine-activated killer (LAK) cells into the metastatic sites in combination with systemic recombinant interleukin-2 (rIL-2) administration in 3 patients with advanced renal cell carcinoma. Leukapheresis was performed once a week and peripheral blood lymphocytes were separated into 2 different subtypes by Percoll gradient centrifugation. These lymphocytes were incubated with rIL-2 for a few days to induce LAK cells. LAK cells were transfered to the metastatic lesions through cannula twice a week. A large iliac bone metastatsis disappered 3 months after the initial LAK cell therapy via a superior gluteal artery. A case of complete disapperance of psoas muscle and para-aortic lymphnode metastaseis as well as partial regression of a lumbar bone metastasis was seen after lumbar arterial infusion treatment. Another case with brain metastasis showed a rapid exacerbation of brain edema after one week's LAK therapy. Our treatment modality seems to be worthwhile and promising for treatment of the advanced renal cell carcinoma.
Transrectal longitudinal ultrasonography was performed in 34 patients with chronic nonbacterial prostatitis. Prostatic stones and cystic lesions were associated with chronic non-bacterial prostatitis in 67.6% and 11.8%, respectively. The annual relapse rates of clinical symptoms were related to the presence of prostatic stones and cystic lesions. Transrectal ultrasonography plays a very important role in predicting the clinical courses of chronic non-bacterial prostatitis.
From November 1981 to November 1987, 35 patients with newly diagnosed advanced prostatic cancer (6 Stage C cases and 29 Stage D2 cases) were treated by chemoendocrine therapy consisting of orchiectomy, diethylstilbestrol-diphosphate and cisplatin. Objective responses were assessed at 3 months after the start of treatment. Of the 35 patients, 8 had PR (partial response) and 27 was objective stable by NPCP criteria. Objective progression was not seen. In analysis of long-term results, the 3-year and 5-year survival rate for total cases were 75.8% and 60.7%, respectively. For Stage C cases, the 3-year and 5-year survival rates were 100% and 100%; for Stage D2 cases, they were 72.2% and 54.2%, respectively. Relapse was seen in 7 (24.1%) of the 29 Stage D2 cases. All of these 7 patients had poorly differentiated adenocarcinoma and most of them had more than 10 bone metastases. As for side-effects, gastroenteric symptoms (nausea and vomiting), anemia and slight liver dysfunction were seen. These results suggest that the chemoendocrine therapy is an effective treatment in newly diagnosed cases of advanced prostatic cancer.
The advancement in image diagnostic methods has been great in recent years and image diagnosis has become indispensable for the diagnosis of renal and other cancers. However, the clinical images are fixed and recorded on film as analog images for storage and the expansion of storage space, the poor efficiency in arrangement and control and the inconvenience of transfer have become big problems. Digitization of the clinical images offers the advantages of solving these problems and of allowing a variety of image analyses to be made easily. The tendecy is for the digitization of all images for medical use in the near future. We applied a handy image analysis system (Shonic GA) using a personal computer as the mainframe and tried to digitize the analog images of a pyelogram, DSA, ultrasonogame, and X-ray CT of renal carcinoma for digital analysis. The results were displayed. This system is handy and easy to operate and thus is useful for the purposes of understanding and gaining experience in digitization and digital analyses of images for medical use.
The urinary N-acetyl-β-D-glucosaminidase (NAG) activities were determined in acute pyelonephritis patients with spinal cord injuries. The urinary NAG activity was significantly elevated in 23 of 31 cases (74%) compared with normal controls. Out of 7 acute pyelonephritis patients without spinal cord injuries, 4 patients (57%) showed significantly elevated urinary NAG activities. The urinary NAG activities were within normal range in 20 patients with acute simple cystitis and 11 patients with chronic complicated cystitis. Out of 6 patients with urethritis, only one case (17%) showed a significantly higher level of urinary NAG activity. Significantly higher levels in urinary NAG activities were observed in 6 of 9 patients (67%) with acute prostatitis and 5 of 9 patients (56%) with acute epididymitis. In patients with spinal cord injuries, having frequent urinary tract infections and complicated pathophysiological conditions, urinary NAG is one of the helpful laboratory findings for the diagnosis of acute pyelonephritis.
We took cultures of many human renal cell cancers and established two cell lines in vitro which were derived from the spindle cell carcinoma of a 67-year-old woman (MR-1) and from the dark cell carcinoma of a 74-year-old woman (MR-2). Using a nude mouse, we established the cell line in vivo (MRV) which was derived from the same patient as that for MR-1. MR-2 was maintained through 140 passages and MR-2 110 passages. MRV was maintained through 7 passages. With passaging, the characteristics, the doubling times and the chromosomal numbers of these cell lines changed, these changes were caused by the transformation, the mutation and the selection of the passaging cells. The study of the sensitivity test of the anti-cancer drugs to the established cell lines was done using the radioisotope uptake assay in vitro and the tumor volume changes in nude mice in vivo. We considered there were differences between the effective drugs used in vitro assay and in vivo assay. As to radioisotope uptake assay, it is difficult to judge the exact effect of the plant alkaloids, which inhibit the cell division and are dependent on the contact time, and we may overestimate the effect of the cytotoxic antibiotics. Further investigation on the methodology of the sensitivity test of the anti-cancer drugs would be necessary for the clinical application.
During about 10 years from November, 1977 to March, 1987, 46 patients with renal pelvic and ureteral tumors were treated at the Department of Urology, Hamamatsu University School of Medicine and the affiliated hospitals. There were 34 males and 12 females with the highest age incidence in the seventies. Histologically, 44 transitional cell carcinomas and 2 squamous cell carcinomas were found. Of the 44 transitional cell carcinomas, 1 was Tis; 13T1, 2T2, 8T3, 15M+(with metastatic lesion), and 5 TX. As to grading, 1 was G1; 24G2, 15G3, and 4GX. Staging was correlated with grading. The 5-year survival rates (Kaplan-Meier's method) were 37% in patients with transitional cell carcinoma. Among patients with transitional cell carcinoma, the 5-year survival rate was 43% for G2 and 42% for G3. As to staging, the 5-year survival rates were 71% and 46% in patients with stage of T1 and T3, respectively. No patient with M+survived longer than 4 years. The 5-year survival rates were 38% and 34% in renal pelvic tumors (24 cases) and ureteral tumors (20 cases), respectively. As to the treatments, the 5-year survival rates after curable treatment (24 cases) and non-curable treatment (20 cases) were 63% and 7%, respectively.
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-Meier's method) were 64% in patients with transitional cell carcinoma; 58% in those with squamous cell carcinoma. In patients with transitional cel 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-Meier's method. The 5-year non-recurrence rates after TUR (137 cases) were 58% overall; 63%, 59%, 58% and 80% in patients with G0, G1, G2 and G3, respectively. As to staging, the 5-year non-recurrence rates were 66%, 57% and 50% in patients with Ta, T1 and T2, respectively. The 5-year non-recurrence rates were 70% and 40% in single papillary and multiple papillary tumors, respectively. No patients with non-papillary tumors were found without recurrence 5 years after TUR. Intravesical recurrence after TUR was significantly more frequent in patients with multiple papillary tumor or non-papillary tumor than single papillary tumor. There was no significant difference with respect to grade, stage and prophylactic treatment in the non-recurrence rate.
Forty-seven patients with high grade invasive bladder cancer were treated with preoperative radiation therapy (910rad by fast neutron or 3000rad by X-ray for two weeks) followed by radical cystectomy and urinary diversion. Stage down effect was observed in 32% of patients when comparison was made between the clinical and pathological stages. Those who showed stage down effect had better prognosis when compared those without it. Histopathological effect of Grade 2B or Grade 3, according to the criteria described by Ohboshi and Shimosato, was noticed in 49% of the patients. Five year survival was as follows: 100% (PT0, PTis), 75% (PT1), 100% (PT2), 47% (PT3), 0% (PT4). These results clearly showed the improvement of prognosis compared to the historical control.
We studied an antiproliferative effect of cancer chemotherapeutic agents, interferon (IFN) and, in particular, their combination effect on renal cell carcinoma. Either of colony formation assay (CFA) or [3H]-thymidine incorporation assay ([3H]-TdR assay) was employed as an in vitro chemosensitivity testing system. When compared, these two systems produced similar results with a good correlation (r=0.97, p<0.01), in the antiproliferative effect of 30 drugs for 4 primary renal cell carcinomas and 5 xenotransplantable renal cell carcinomas. In vitro chemosensitivity test (CFA or [3H]-TdR assay) screened successfully only 5 “sensitive” drugs (7.9%) out of a total 63 cancer chemotherapeutic agents for 24 human renal cell carcinoma. This comfirmed the findings reported by others. In the study of the antiproliferative effect of a cancer chemotherapeutic agent, human lymphoblastoid interferon (HLBI) and their combination on human renal cel carcinoma cell line (SMKR2). Each of VBL, MTX or HLBI tended to suppress [3H]-TdR uptake in a dose-dpendent manner. The combination of VBL (0.05μg/ml) and HLBI (102 or 103IU/ml) produced a subadditive effect, and that of MTX (0.1μg/ml) and HLBI 102IU/ml produced a synergistic effect on the human renal cell carcinoma cell line, the effect which is evaluated by Valeriote and Lin's criteria of combination. In particular, the synergistic effect by MTX and HLBI under the clinically achievable drug concentration seems important, when its clinical application is considered.
Acute focal bacterial nephritis (AFBN) is one of the acute renal infections, its entity can be distinguished from other renal infectins by the findigns of sonography and computed tomography. There is no evidence of liquefaction in focal masses of AFBN in contrast to renal abscess. We present two cases with AFBN. The first case was a 52-year-old man with diabetes mellitus and benign prostatic hypertrophy. The second case was a 24-year-old woman with bilateral vesico-ureteral refluxes. Although their initial symptoms mimicked those of acute pyelonephritis, the findings of sonography and computed tomography revealed renal masses. They were treated with anti-microbial agents, and showed rapid improvement on both clinical symptoms and renal masses.
A case of prostatic cancer treated with an LH-RH analogue depo-preparation was found to have a mediastinal thymoma which was later removed by surgery. The association of thymoma and prostatic cancer has not been documented in the world literature, and it remains to be elucidated whether the occurrence of the both tumors is a coincidence or etiologically inter-related.
A 63 year old man, having right renal cell carcinoma which was found after initial symptoms of left supraclavicular tumor and gross hematuria, is presented. The points to note with this case are; (1) An unusual production of alpha-fetoprotein (AFP), (2) Being discovered at a very advanced stage and that the disease progressed rapidly (at initial presentation the patient had lymph nodes metastases from the paraaorta, mediastinum to the left supraclavicular region. Later the patient had a recurrent tumor in the left supraclavicular area and multiple cutaneous metastases), (3) Various modalities of treatment were given (right nephrectomy, abdominal lymph nodes dissection, resection of the supraclavicular and mediastinal lymph nodes metastases, hyperthermia combined with irradiation for the recurrent tumor in the supraclavicular region and systemically adoptive immunotherapy with tumor infiltrating lymphocytes). During this treatment course, the drift of serum AFP showed a good correlation. The possiblity of AFP as a tumor marker of renal cell carcinoma in selected cases was presented and the suitablity of the treatments performed to this patient was discussed.