IMMUNE REACTIONS IN PATIENTS WITH BLADDER AND PROSTATIC CANCER1

Although there are many reports of cellular immune reactions in bladder and prostatic carcinoma patients, few have demonstrated the presence of humoral reactivity. The use of microtechniques, especially the enzyme-linked immunosorbent assay (ELISA), has made sequential studies possible on patients with early or small tumours. Using this assay, the presence of serum antibodies has been demonstrated in both bladder and prostate patients, the specificities of these reactions being checked against a battery of different tumours and normal tissues. In many of the patients, with low or transient antibody levels, the presence of circulating immune complexes was shown by the Raji cell assay and analysed by double counter-current immunoelectrophoresis (DCIE). The content of these complexes appeared to be either antibody and tumour antigen or antibody and antiimmunoglobulin. In a small series of cryosurgically treated prostatic carcinoma patients, the course of these antibodies was monitored over several weeks, and the fluctuations in antibody levels were related to the presence of these different types of complexes.     

THE MOLECULAR CHARACTERISTICS OF BLADDER CANCER IN YOUNG PATIENTS

Purpose

The molecular characteristics of bladder cancer in children and young adults remain largely undefined. We sought to identify common molecular changes in bladder tumors in young patients using standard immunohistochemical and interphase cytogenetic methods.

Materials and Methods

We retrospectively evaluated 73 bladder tumors removed from patients younger than 30 years for the p53 tumor suppressor gene product using immunohitochemical techniques and numerical aberrations of chromosomes 9, 17, X and Y.

Results

Regardless of stage, immunohistochemical evidence of p53 gene product over expression was found in the majority of tumors studied. Numerical abberations (mosomy) of chromosome 9 were rare. Aneuploidy of chromosome 17 was common, particularly in carcinoma in situ and invasive bladder cancer.

Conclusions

These data suggest that immunohistochemical evidence of p53 gene product over expression is common in bladder cancer in young patients. Further prospective analysis of lesions in this population may help to establish a comprehensive molecular progression model for urothelial neoplasms.     

PREDICTIVE VALUE OF p53 AND pRb IMMUNOSTAINING IN LOCALLY ADVANCED BLADDER CANCER TREATED WITH CYSTECTOMY

Purpose

We elucidate the association between altered immunostaining for retinoblastoma gene protein (pRb) and p53 nuclear proteins, and cancer specific death in patients treated with cystectomy for locally advanced bladder cancer.

Materials and Methods

The hospital records of 173 patients treated with cystectomy for advanced urothelial bladder cancer between 1967 and 1992 were retrospectively reviewed. Representative biopsies obtained before treatment were sectioned and stained using the standard immunohistochemical technique with antibody DO-7 (p53) and antibody PMG3-245 (pRb). A tumor was considered to have an altered p53 expression if 20% or more of tumor cells exhibited nuclear staining. Similarly, if no tumor cell had nuclear immunostaining the tumor was considered to have an altered pRb expression.

Results

An altered expression was observed for p53 in 98 tumors (57%) and for pRb in 60 (35%). In a proportional hazards analysis no association was found between an altered expression of pRb or p53 and cancer specific death. This finding was also true in another analysis when the results of immunostaining for pRb and p53 were combined.

Conclusions

An altered expression for pRb and/or p53 was not correlated to cancer specific death. Thus, these parameters could not be used as predictors of treatment outcome after cystectomy for locally advanced bladder cancer.     

DETECTION OF BACILLUS CALMETTE-GUERIN IN THE BLOOD BY THE POLYMERASE CHAIN REACTION METHOD OF TREATED BLADDER CANCER PATIENTS

Purpose

Following intravesical bacillus Calmette-Guerin (BCG) instillation, we attempted to detect BCG in the blood using the polymerase chain reaction (PCR) method and correlate these findings with the occurrence of major complications due to this treatment.

Materials and Methods

Intravesical BCG immunotherapy was given to 22 consecutive patients with superficial bladder tumors. In 2 patients the BCG instillation has to be discontinued due to serious side effects of therapy. Blood samples (252 aliquots) were obtained from 126 BCG courses in 22 cases, and 2 additional samples (4 aliquots) were obtained from 1 patient 1 and 3 months after cessation of therapy. All blood samples were analyzed by the PCR technique for detection of deoxyribonucleic acid tuberculosis Mycobacterium tuberculosis.

Results

Of the 126 blood samples 9 (7.1%) were PCR positive for M. tuberculosis. These 9 positive samples belonged to 3 patients, all of whom were among those 4 patients who had major clinical side effects.

Conclusions

We demonstrated that rapid and sensitive detection of mycobacteremia by PCR correlated with the clinical course of these patients. We also demonstrated that PCR can be used to monitor BCG in the blood after antituberculous therapy. The early, fast and accurate diagnosis of BCG in the blood by PCR may alter the serious clinical course of these patients by initiation of specific treatment early. However, further extensive studies are needed to validate these results.     

TUMOR LOCALIZATION AND SYSTEMIC ABSORPTION OF INTRAVESICAL INSTILLATION OF RADIO-IODINATED IODODEOXYURIDINE IN PATIENTS WITH BLADDER CANCER

PURPOSE: We evaluated tumor uptake and systemic distribution of intravesically instilled iododeoxyuridine (IUdR) in patients with superficial bladder cancer. MATERIALS AND METHODS: We performed 24 intravesical instillation studies in 11 patients with a mean age of 71 years. Radio-iodinated IUdR was administered through a Foley catheter. Gamma camera imaging was done after instillation and after 5 to 7 bladder irrigations. Tumor uptake was estimated by region of interest analysis. Bladder biopsy samples and surgical tumor specimens were tested for acid insoluble (deoxyribonucleic acid incorporated) radioactivity. Blood samples were obtained and analyzed for systemic absorption. RESULTS: Imaging was positive in all patients with bladder cancer. Average tumor uptake plus or minus standard deviation was 0.185+/-0.120% of the instilled dose. Preferential uptake of IUdR in the tumor was observed in all 6 patients undergoing tissue analysis. The tumor-to-normal bladder ratio ranged from 3.2 to 74,000 (median 202). Systemic absorption of IUdR was minimal. Blood sample analysis performed after intravesical instillation in all 11 cases revealed an average uptake of 3.2x10(-5)% instilled dose per ml. (range 0.69x10(-5) to 6.7x10(-5)) in the systemic circulation. Instillation within 24 hours after transurethral bladder tumor resection in 5 cases resulted in a higher but not dangerous average systemic uptake of 7.3x10(-4)% instilled dose per ml. (range 1.3x10(-5) to 2.6x10(-3)). Instillation 1 to 4 weeks after transurethral surgery in 8 cases resulted in no increased systemic absorption with an average blood level of 3.4+/-1.8x10(-5)% instilled dose per ml. There was no detectable distribution of radioactivity into other organs, including the thyroid. We noted no evidence of systemic toxicity in the study. CONCLUSIONS: Intravesical instillation of radio-iodinated IUdR achieves selective localization in the bladder tumor with minimal uptake by the normal bladder and minimal systemic absorption. The use of intravesical IUdR therapy for bladder cancer appears to be promising and requires further study.     

THE STATUS OF BLADDER. P. RESERVING THERAPEUTIC STRATEGIES IN THE MANAGEMENT OF PATIENTS WITH MUSCLE–INVASIVE BLADDER CANCER

The recommended treatment for medically fit patients with muscle–invading bladder cancer is usually radical cystectomy. However, transurethral resection of the tumor, partial cystectomy, irradiation and systemic chemotherapy are each effective in some patients. These latter treatments allow bladder preservation and cure as an alternative to radical cystectomy although when used unselectively the survival rates are inferior to those of radical cystectomy. The updated results of conservative surgery, radiation therapy and systemic chemotherapy as monotherapy, as well as strategies of combined modality treatment were reviewed. Based on this review many areas of consensus were reached which include: 1. The primary goal of any treatment for a patient with muscle–invading bladder cancer is survival; bladder preservation in the interest of quality of life is a secondary objective. 2. Only a small proportion of carefully selected patients may be cured by transurethral surgery alone, or by partial cystectomy alone. 3. Radiation therapy is currently the standard bladder–preserving therapy against which all other bladder–preserving methods must be compared. 4. Systemic chemotherapy as monotherapy is inadequate and cannot be recommended. 5. The addition of cisplatin–containing systemic chemotherapy to radiation therapy or conservative surgery appears to improve local control. While no multi–modality therapeutic regimen has yet been shown to be clearly optimal with regard to local efficacy and minimizing toxicity, monotherapy for bladder preservation is probably not desirable as a routine approach. 6. Deferring the patient from immediate cystectomy does not appear to compromise survival, nor does the addition of primary systemic chemotherapy appear to significantly increase the morbidity of cystectomy or radiotherapy. 7. All patients treated by .bladder–preserving therapy must return to the urologist for regular cystoscopic follow–up so that additional therapy may be started at the earliest opportunity if relapse occurs. 8. Bladder substitution is suboptimal compared with a normally functioning, disease–free bladder. 9. If alternatives to cystectomy are not considered, little progress will be made in the treatment of muscle–invading bladder cancer. 10. Randomized phase III trials must be performed to establish the role of optimal combined modality treatment for bladder preservation, but patient recruitment into such trials may prove difficult unless urologists are prepared to open their minds to the possibility that cystectomy may not be the best treatment for all patients with muscle–invading bladder cancer. Further, urologists must be prepared to have their patients randomized into phase III protocols and investigators must not allow premature publication of findings.     

THE FATE OF PATIENTS WITH LOCALLY ADVANCED BLADDER CANCER TREATED CONSERVATIVELY WITH NEOADJUVANT CHEMOTHERAPY, EXTENSIVE TRANSURETHRAL RESECTION AND RADIOTHERAPY: 10-YEAR EXPERIENCE

Purpose

We asses the results of bladder preservation for infiltrating cancer. The potential for neoadjuvant chemotherapy followed by extensive transurethral resection and radiotherapy was evaluated in 40 patients with T2-T4a G2-G3 bladder carcinoma.

Materials and Methods

From 1983 to 1995, 40 patients with bladder cancer underwent bladder sparing treatment, consisting of neoadjuvant chemotherapy, extensive transurethral resection and radiotherapy. Most patients had T3G3 cancer. A deep transurethral resection biopsy was performed before and after chemotherapy, and an extensive transurethral resection was repeated at the end of radiotherapy. Of the patients 30 received cisplatin and methotrexate and 10 also received vinblastine. Total dose of radiotherapy was 60 to 65 Gy. Recurrent superficial tumors were treated transurethrally. Radical cystectomy was considered for persistent or recurrent invasive disease.

Results

Complete response occurred in 19 patients (47.5%) after chemotherapy, and in 8 patients after transurethral resection and radiotherapy (67.5%). Within 10 years 8 responding patients (30%) had local recurrences and 3 underwent cystectomy. Of the patients 14 (35%) are alive, including 13 with no evidence of disease (mean survival 65 months), 5 died of unrelated disease and 21 (52.5%) died of distant metastases (mean survival 28 months). Of the 21 patients 14 had residual tumor after radiotherapy, 3 presented with distant metastases after vesical infiltrating recurrence and 4 had distant metastases in the absence of locoregional recurrence. In 22 patients (55%) the bladder was salvaged. Patients with complete response to chemotherapy had a low risk for recurrent infiltrating tumors and metastases.

Conclusions

Complete tumor control was maintained at 5 years in more than 50% of the patients treated conservatively. Bladder salvage is feasible in select patients.     

转移性肝癌外科治疗及预后因素分析

目的 为探讨转移肝癌肝切除术疗效及影响预后因素,对７８例转移性肝癌切除术进行性分析。方法 我院从１９８２年１月至１９９４年１月对７８便肝转移癌的病人,在原发癌根治术的基础上行肝切除术。其中４８例原发癌结肠癌,３０例为非结直肠癌,随访生存期并分析影响预后诸因素累进要转移性肝癌切除术后总的１、３、５的眩分别为７６．９１％、３９．６％、２５．６４％。肝转移癌数目超过２个的病人５年生存率为０％,而转移灶少     

肝移植患者术后检测AKBR的临床意义

目的 探讨检测动脉血酮体比（ＡＫＢＲ）在肝移植术后的临床作用。方法 将二例肝移植患者术后动脉检测ＡＫＢＲ３０天,并与其它标志供肝活力的指标作比较。结果 ＡＫＢＲ在肝移植术后的变化与其它标志供肝活力的指标有相关性,且较其它指标敏感。结论 ＡＫＢＲ可作为特异性判断肝移植是否存活及肝移植预后和转归的指标。     

PROGRESSION IN AND SURVIVAL OF PATIENTS WITH LOCALLY ADVANCED PROSTATE CANCER (T3) TREATED WITH RADICAL PROSTATECTOMY AS MONOTHERAPY

Purpose

We determine the progression and survival rates in patients with locally advanced prostate cancer treated with radical prostatectomy without adjuvant treatment, and investigate subgroups of patients who may not benefit from this treatment.

Materials and Methods

Radical prostatectomy was performed in 83 patients with T3 prostate cancer. The patients were divided in subgroups with T3G1 to 2 and T3G3 tumors, which were evaluated for clinical progression, local recurrence, distant metastases, biochemical progression, and overall and cancer specific survival at 5 and 10 years by Kaplan-Meier curves. The results were compared to those of 190 patients with locally confined tumors.

Results

At 5 and 10 years overall survival was 75 and 60%, and cancer specific survival was 85 and 72%, respectively. At 5 and 10 years clinical progression was 41 and 69%, local recurrence 18 and 44%, and distant metastases 31 and 50%, respectively. Biochemical progression at 5 years was 71%. Patients with poorly differentiated tumors showed significantly lower survival and higher progression rates compared to those with well or moderately differentiated tumors. Progression and survival in patients with T3G1-2 tumor were not significantly different from those for patients with locally confined tumors.

Conclusions

Radical prostatectomy as monotherapy in patients with locally advanced non-metastatic prostate cancer (T3) produces acceptable results in those with well or moderately differentiated tumors. The results of progression and survival are not significantly different from those in patients with locally confined prostate cancer. However, patients with poorly differentiated tumors (T3G3) have early progression and need adjuvant treatment following surgery.     

SECOND PRIMARY MALIGNANCIES IN T1-3N0 PROSTATE CANCER PATIENTS TREATED WITH RADIATION THERAPY WITH 10-YEAR FOLLOWUP

Purpose

The risk of patients with prostate cancer to have second primary malignancies is unclear. Population and autopsy based studies have shown no increased risk, which is at variance with several institutional analyses. A retrospective review was performed with comparison to expected cancer data from the Connecticut Tumor Registry.

Materials and Methods

Records of a cohort of prostate cancer patients treated with staging pelvic lymphadenectomy and definitive radiotherapy between November 1, 1974 and July 7, 1987 were reviewed. Median potential followup from date of diagnosis was 10.9 years.

Results

Of the 164 patients 150 (91.5%) had followup to death or to August 1995, with data available in part on 4 of the remaining patients. In 43 patients 51 second primary malignancies developed. Increased frequency of lymphomas, and kidney, bladder and rectal lesions (all p <0.001) was observed concurrently with diagnosis of prostate cancer, although this may be due to bias since full staging for the prostate cancer may have led to their diagnosis. An increased frequency of renal lesions in the 1 to 4-year followup period (p = 0.032) also was observed. Two sarcomas and a leukemia were putatively radiation induced but their frequency was not significantly different from the comparison baseline.

Conclusions

Much of the apparent increase in second primary malignancies associated with prostate cancer noted by some authors may be attributed to bias in the staging process. Renal cancers may occur more frequently in patients with prostate cancer but the distribution of these lesions is inconsistent with a field defect mechanism of cancer induction.