(Purpose) To study whether nephron sparing surgery is suitable or not for the operation for renal cell carcinoma (RCC) by examing the style of the existence and proliferative potential of satellite tumor lesions (STL). (Method) We made whole area histological sections on 58 cases of RCC and investigated histological behavior and proliferative potential of RCC using H & E staining and silver staining for Argyrophilic Nucleolar Organizer Resions (AgNORs) of following lesions: main tumors, STL, adenomas (AD), and dysplastic foci (DF) in which the latter two are supposed to be preneoplastic lesions. (Result) In 58 cases, STL were observed in 27 cases (46.6%) and either AD or DF was noted in 19 cases (32.8%). Thus, either of above lesions including STL, AD and DF was found in 37 cases (63.8%). The frequency of STL had no relationship with main tumor size, but tended to be higher in high grade and/or high stage cases. STL were located more than 2cm away from the margin of main tumors in 6 (22%) of 27 cases with STL. The numbers of AgNORs in each high power field were 5.09±1.53 (mean±SD) in main tumors, 4.24±1.36 in STL, and 2.27±0.07 in AD and DF, respectively. (Conclusion) These results suggest that STL are composed of cells with accelerated proliferative potential, and that nephron-sparing surgery had the risk of remaining STL. Therefore, further studies are needed to elucidate whether STL have any relation to local recurrence after nephron-sparing surgery.
(Purpose) Cell adhesion molecules (CAMs) have been considered to play key roles in cancer metastasis through binding of cancer cells to the endothelial cells or matrix. We have found that constitutive expression of E-selectin, ICAM-1 (intercellular adhesion molecule-1) and VCAM-1 (vascular cell adhesion molecule-1) on the cell surface of prostate cancer cell lines, PC-3 LNCaP, and DU145. In an attempt to explain the highly metastatic potential of these cells, we investigated expression of CAMs. Since these expressed CAMs are known to be regulated by a transcription factor NFκB. We have examined if NFκB is activated in these prostate cancer cell lines. (Material and Method) Expression of E-selectin, ICAM-1, Sialyl-Lewis X, LFA-1 (lymphocyte function-associated antigen-1), integrinα 4, and integrinβ1 were examined by indirect immunofluorescent staining and Western blotting using specific monoclonal antibodies. We then examined whether pro-inflammatory cytokines known to stimulate NFκB, IL-1 and TNF, could drive the nuclear translocation of NFκB. Ten ng/ml of recombinant human IL-1β or TNFα was added to the cell culture and the CAMS level, as well as nuclear translocation of NFκB, was examined. (Results) The staining levels of ICAM-1, VCAM-1, and integrinβ1 were highly elevated in PC-3 and DU145. In surprising, NFκB was retained in the cytoplasm (as an inactive form) and not detectable in the nucleus (active form) as demonstrated by immunofiuorescence. Although time-dependent expression of these molecules were explored, the level of ICAM-1 and VCAM-1 on the cell surface were unchanged. However, nuclear translocation of NFκB could be induced. (Conclusion) These observations indicate that while the signaling pathway to NFκB is intact, it is not directed to induction of its target CAM genes. It is possible that other transcription factors might be involved in these cells and that they might to be constitutively stimulated during the carcinogenesis of prostate cancer.
(Background) Chromosomal aberration and DNA ploidy pattern are regarded as prognostic markers of the bladder cancer. In this paper, numerical chromosomal aberrations were analysed by interphase fluorescence in situ hybridization (FISH) for the cases with bladder cancer. (Methods) FISH was carried out on touch smear of 35 cases of transitional cell carcinoma of the urinary bladder. DNA probes were digoxigenin labeled α/β-satellite probes for chromosome 1, 7, 9, 11, 17, Y. FISH signals were counted using confocal laser microscope (LSM GB 200, OLYMPUS). Touch smear preparations were also examined with image cytometer (CAS 200, Becton Dickinson) and DNA index was obtaind. (Results) Numerical chromosomal aberrations were observed in 9 of 21 (42.9%) diploid cases and in all 14 non-diploid cases. Among 6 kinds of chromosome examined imbalance was observed and most common imbalance was loss of chromosome 9 (11 cases, 32.4%). (Conclusion) Even in the diploid tumors, chromosomal aberration was observed. Combined analysis of chromosomal aberration and DNA ploidy pattern was easily and quickly performed in our series. Clinical application could be possible and possess diagnostic and prognostic value.
(Background) The objective of this study is to evaluate prognostic factors of non-metastatic renal cell carcinoma using univariate and multivariate statistical methods. (Methods) 390 patients who were performed radical surgery in our hospital between 1960 and 1994 were enterd to this study. Kaplan-Meier method with log-rank test and Cox's proportional hazard model were used for statistical analysis. (Results) Chief complaints, tumor localization on kidney, tumor size, fever, hemoglobin, C-reactive protein, erythrocyte sedimentation rate, immunosuppresive acidic protein, operative method, blood loss, histologic grade, cell type, pT, pN and pV revealed to have prognostic statistical significance in the univariate analysis. Whereas, sex, age, blood type, hypertension, affected side and preoperative embolization did not. In the multivariate analysis of the preoperatively evaluable factors, CRP, tumor size and tumor localization proved to be significant prognostic predictors in this order. When the pathological factors were included to the multivariate analysis, pV, historogic grade and pN revealed to be significant prognostic predictors in this order. (Conclusion) These results suggest that pathological factors were significant prognostic predictors for non-metastatic renal cell carcinoma.
(Background) We investigated the propriety of neoadjuvant chemotherapy and the possibility of bladder preservation based on clinical and pathological responses in invasive bladder cancer. (Method) Nineteen cases of invasive bladder cancer which had been subjected to two courses of neoadjuvant chemotherapy followed by radical cystectomy were analyzed. (Results) The overall response rate was 79% (5/19), and 7 cases (37%) had a pathological complete response (pCR). Many cases showed degeneration or necrosis of cancer cells and infiltration of lymphocytes around the original cancer sites. Foamy macrophage or fibrous change was observed in high response cases. Thickening of the bladder wall were found after chemotherapy in such cases, which led to over-staging of the CT scan. We deviled invasive bladder cancers into four different types based on gross tumor appearance and histology from TUR biopsy specimen: Type 1 which has an nodularly elevating pedunculated structure: Type 2A which has an elevating nonpedunculated structure with partly papillary component and no lymph vessel invasion: Type 2B which has an elevating nonpedunculated structure with partly papillary component and marked lymph vessel invasion: and Type 3 which has a nonelevating diffuse invasive structure with CIS lesion. The therapeutic effect was greater than grade 2 in 7 cases out of 8 (88%) Type 1, 2 cases out of 3 (67%) Type 2A, no case out of 6 (0%) type 2B, and 1 case out of 2 (50%) type 3. (Conclusion) This classification will indicate the appropriate preoperative treatment for invasive bladder cancer, and will be useful when formulating criteria for bladder preservation. In particular, Type 1 or Type 2A is chemosensitive and may be considered for bladder preservation.
(Background) The long-term results of systematic treatment based on overnight simultaneous monitoring of electroencephalography (EEG) and cystometry in the patients with enuresis were evaluated. (Methods) From January to December, a total of 213 patients were classified into 3 types. Enuresis Type I: such cases show a normal cystometrogram (CMG) with an awakening response on the EEG before enuresis, but they do not awake. Enuresis Type IIa; such cases show a normal CMG without an awakening response on the EEG. Enuresis Type IIb; such cases show an abnormal CMG with no awakening response on the EEG. When such cases enter the deep sleep stage, continuous uninhibited contractions of the bladder are observed on the CMG. 136 cases were of Type I, 20 cases of Type IIa, and 57 cases of Type IIb. (Results) Out of 213 patients who were followed up for 2 years, cured cases were 94 (44%), effective cases were 81 (38%) and unchanged cases were 38 (18%). In 136 patients with Type I, cured cases were 71 (52%), effective cases were 50 (37%) and unchanged cases were 15 (11%). In 20 patients with Type IIa, cured cases were 8 (40%), effective cases were 9 (45%) and unchanged cases were 3 (15%). In 57 patients with Type IIb, cured cases were 15 (26%), effective cases were 22 (39%) and unchanged cases were 20 (35%). The age of the effective group, which included cured cases and effective cases, was significantly higher than that of the unchaged group. In enuresis Type I, the percentage of the patients with incontinence in daytime were significantly in the unchanged group than in the effective group. No significant differences in the frequency of enuresis and the percentage of the patients who had awakened spontaneously by urinary sensation were found between the two groups. (Conclusions) The therapeutic response was best in enuresis Type I and worst in enuresis Type IIb. The patients, in whom not only frequency of enuresis but also type of enuresis was unchanged by systematic treatment for two years, was approximately 10% across the types. Accordingly they were thought to be non-responders to this systematic treatment.
(Background) Monoclonal antibodies (mABs) against urinary proteins originated from renal tubules were obtained in order to find a possible tumor marker for renal cell carcinoma. (Methods) Urine samples were collected from healthy adult males. After removal of Thamm-Horsfall protein (THP) by sodium chloride precipitation, supernatant urine was ultrafiltered, thus, THP-free urinary proteins were obtained. Then, proteins of plasma origin were removed by circulating the urinary proteins through an affinity column which contained immobilized rabbit anti-human whole serum immunoglobulins. BALB/c mice were immunized with the THP- and plasma protein-free urinary proteins. The spleen cells were fused with mouse myeloma cells. Hybridomas were screened by indirect immunofluorescence of fresh frozen kidney tissue sections using culture supernatants. (Results) Five hybridomas producing mAbs which reacted with renal tubular segments were established. One mAb reacted strongly with distal renal tubules. Using this mAb, formalin fixed and paraffin embedded sections of 39 renal cell carcinomas were stained by immunoperoxidase method. Twenty-six of the 39 cancer tissues (66.7%) were stained positive. According to the histological classification, positive staining rate of clear cell subtype, granular cell subtype and mixed subtype was 75% (6/8), 80% (8/10) and 66.7% (6/9), respectively. According to the tumor grade, positive staining rate of G1, G2, G3 was 66.7% (6/9), 71.4% (15/21) and 55.5% (5/9), respectively. (Conclusion) These findings indicate that most of renal cell carcinomas were originated from common precursor cells for both proximal and distal tubules, because normal proximal tubular cells were not stained by the mAb.
(Background) The side effects of steroid are serious problems in renal transplant patients. However, withdrawal of steroid has been controversial. We evaluated the benefits and risk of early steroid withdrawal after renal transplantation. (Patients and Methods) The outcomes of early steroid withdrawal from triple immunosuppressive drug therapy were analyzed in four living related and one cadaveric renal transplant recipients. The dosage of steroid was gradually reduced and the time of steroid withdrawal after transplantation was 5 to 7.5 months. (Results) Four Patients have been able to be free from steroid and maintained stable graft functions and normal urinary findings for 14 to 33 months after withdrawal. The findings of rejection were not observed in the graft specimens obtained by serial biopsies. One patient who received a living related graft developed an increase in serum creatinine level and proteinuria two weeks after discontinuation of steroid. The serum creatinine level returned to that before withdrawal and proteinuria disappeared by steroid readministration. Long term side effects of steroid were not observed in 4 patients with successful steroid withdrawal. (Conclusion) These results suggest that steroid withdrawal about 6 months after transplantation can be accomplished without jeopardizing graft function in selected renal transplant recipient and the withdrawal in the early stage is preferred for reducing the side effects. Careful and long-term follow up are required to assess the further risk and benefit of steroid withdrawal on immunosuppressive morbidity.
A 49-year-old female was admitted with chief complaint of fecaluria on March 4th 1993. A radiation therapy had been performed for uterocervical cancer 18 years ago. The small intestine and bladder was detected by DIP and cystogram simultaneously. It was diagnosed as an ileovesical fistula. A segmental resection of the ileum with partial cystectomy was performed on March 23rd. Histopathologically, the ileum showed a radiation enteritis. Eventually, we diagnosed that this ileovesical fistula was caused by radiation. After operation, an incompletion of suture occured. So we made an ileostomy secondarily and performed hyperbaric oxygen therapy. The patient was getting well temporarily but died of gastric hemorrhage on May 1st.
A forty four-year-old house-wife presented with gross hematuria and difficulty on urination of a year and 3 months duration. Transvaginal examination showed a hen egg-sized soft mass on the anterior vaginal wall. Urine cytology revealed many clusters of malignant cells suggestive of adenocarcinoma. Cystourethrography revealed two urethral diverticula, whose orifices were cystoscopically located at the proximal and distal side of urethral sphincter, respectively. By vaginal digital pressing, a soy-bean sized papillary tumor came out of the proximal diverticulum. Histopathological examination of the biopsied tumor suggested poorly differentiated transitional cell carcinoma with inverted growth. Under the diagnosis of carcinoma arising in the urethral diverticulum, anterior pelvic exenteration with formation of Indiana pouch was carried out. The tumor in the proximal diverticulum was histologically composed of a variety of adenocarcinomatous pattern, such as tubular, papillary and cystic structure with a distinctive pattern of tubules lined by a superficial layer of hobnail cells, leading to the diagnosis of mesonephric adenocarcinoma of urethral diverticulum. Postoperative radiation therapy was given because the diverticulum was adherent to the pubic bone, though lymph node metastasis was negative. She has been well with no evidence of the disease for 1 year and 4 months after the operation. Although the histogenesis of female urethral mesonephric adenocarcinoma was still controversial, this case seems to be the forty fourth case in the world literature.