Tumor control of locally advanced prostate cancer following combined estramustine, vinblastine, and radiation therapy.

PURPOSE: A prospective phase II study was carried out to determine whether estramustine phosphate (EMP) plus vinblastine (VBL) in combination with radiotherapy (RT) would improve the control of locally advanced prostate cancer. The rationale for combining EMP plus VBL with RT was based on the clinical and radiobiological data that EMP plus VBL acted as an excellent radiation sensitizer in cultured human prostatic carcinoma cells with the property of tissue selectivity. The combined EMP and VBL were well tolerated in the phase II clinical study of patients with advanced prostate cancer. MATERIALS AND METHODS: Between January 1991 and July 1996, 65 patients, stage T2 (B2) through stage T4 (D1), were entered into the study. Gleason pattern scores ranged from 4 to 10. Pretreatment prostate-specific antigen (PSA) was as follows: < 20 in 21 patients (32%), 20 to 50 in 23 patients (35%), and > 50 in 21 patients (32%). The median age was 70 years (55-83). All patients were treated with megavoltage beam radiation with a total tumor dose of 65 to 70 Gy. Oral EMP 450 mg/m2 daily and VBL 3 mg/m2 weekly were given concomitantly in 46 patients during the 7- to 7 1/2-week course of radiotherapy. RESULTS: All patients showed prompt and complete tumor regression on digital rectal examination at 6 weeks following the completion of treatment. Median follow-up time is 43 months (3-65). PSA fell to an undetectable level by 6 weeks in 56 of 65 patients (86%). For the whole group at 5 years clinical control was 81%, but biochemical control (PSA < 4 ng/mL) was 48%. The likelihood of being free of biochemical relapse at 5 years was a function of initial PSA value (PSA < 20 in 64% of the cases, 21-50 in 60%, and > 50 in 0%). The biochemical-relapse-free survival at 5 years for each stage was T2, 49%; T3, 38%; and T4, 17%. In particular, a group of patients with pretreatment PSA levels of 20 to 50 ng/mL responded quite favorably to the present combined regimen in that only 40% of the patients showed a biochemical failure at 5 years, considering the high level of initial PSA. CONCLUSIONS: The present combined approach is effective in achieving a high rate of tumor control with no disproportionately enhanced side effects. The rapid regression of the tumor nodules and sustained freedom from biochemical relapse suggest excellent long-term tumor control, especially in the group of patients with pretreatment PSA levels of 20 to 50 ng/mL.

Changes in in vivo optical properties and light distributions in normal canine prostate during photodynamic therapy.

The optical absorption and transport scattering coefficients of normal prostate tissue have been measured in vivo in dogs. The measurements were made at 630 nm before and during treatment by Photofin photodynamic therapy using interstitial optical fiber fluence-rate detectors. Corresponding measurements were made ex vivo, at 1 week after treatment, in the contralateral lobe. The optical properties were derived by applying a diffusion theory model to the fluence rates measured at two different source-detector fiber distances. While the in vivo pretreatment and in vivo contralateral post-treatment absorption and scattering values are self-consistent and in agreement with published data, significant changes were observed in the light fluence rates, and hence in the derived optical properties, during light irradiation. The possible causes of such changes are considered, and the implications for light dosimetry in photodynamic therapy are discussed.

Autocrine motility factor receptor as a possible urine marker for transitional cell carcinoma of the bladder.

PURPOSE: To determine whether autocrine motility factor receptor (AMFR) is detectable in the urine of patients with transitional cell carcinoma (TCC) of the bladder. MATERIALS AND METHODS: We assayed the urine of 89 patients with bladder pathology and 28 normal controls for AMFR. A monoclonal antibody to AMFR was used. RESULTS: All patients with muscle-invasive TCC tested positive for AMFR. Autocrine motility factor receptor was detectable for 80% of superficial tumors, with a correlation between AMFR and tumor grade. Seventy-five percent of control urines tested negative. CONCLUSIONS: Autocrine motility factor receptor is detectable in the urine of patients with TCC. Long-term follow-up and refinements in the assay should define the marker's utility for detection and prognosis.

Prognostic significance of DNA quantitation in stage D1 prostate carcinoma with the use of image analysis.

BACKGROUND: A characteristic feature of prostatic adenocarcinoma is its great variation in biologic behavior. This variation and the observation that most carcinomas are of intermediate grade make standard histologic grading of limited value in determining the prognosis of a patient. METHODS: DNA quantitation with the use of computer-assisted image analysis on Feulgen-stained nuclei was performed on the metastatic lymph nodes from patients with Stage D1 prostate carcinoma to determine whether ploidy was a useful predictor of survival or progression. The Gleason histologic score of the primary tumor, the number and extent of lymph node metastases, and the progression and survival intervals were documented. Treatment modalities included pelvic lymph node dissection, radical prostatectomy, external beam radiation therapy, and iodine 125 implantation. RESULTS: DNA ploidy quantitation showed that 65% (33 of 51) of cases were aneuploid, 2% (1 of 51) were tetraploid, and 33% (17 of 51) were in the diploid range. Progression to Stage D2 disease occurred in 76% of the patients with aneuploid cases and 53% of those with cases in the diploid range. CONCLUSION: There was a significant difference in progression between the two ploidy groups (Cox regression analysis, P less than 0.05).

Radical surgery in the treatment of localized carcinoma of the prostate.

New methods of early detection combined with recent advances in surgical techniques have resulted in more patients undergoing radical surgery for treatment of localized carcinoma of the prostate. Over 350 radical prostatectomies have been performed by our group since January 1987. We review the role of radical prostatectomy in the treatment of prostate cancer and our experience with 100 patients undergoing radical retropubic prostatectomy since the advent of nerve-sparing techniques to preserve potency.

The current role of prostatic acid phosphatase and prostate-specific antigen in the management of prostate cancer.

Although PSA is considered to be the true serum marker of prostatic tissue and a valuable indicator for cancer in the gland, knowledge of its significance and limitations is essential to its use for screening, staging, and monitoring CAP. PSA may be used in conjunction with DRE for early detection of CAP. Men with abnormal DRE should have a TRUS with or without biopsy. In men older than 50 years and with negative DRE and PSA < 4 ng/mL, annual evaluations are prudent. In patients with a PSA range of 4.0 to 9.9 ng/mL, high-risk groups such as black males and those with a positive family history should have TRUS. Males with negative DRE in the PSA range of 4.0 to 9.9 ng/mL should have TRUS to evaluate prostate volume and PSAD. Biopsy should be considered in those with PSAD > 0.15. Men with PSA > 10 ng/mL, even in the presence of an enlarged benign prostate, should have multiple directed biopsies under TRUS guidance.

Evaluation of the Velcom-100 pulse Doppler cardiac output computer.

The use of Doppler ultrasound as a means of obtaining cardiac output (CO) measurements quickly, easily, and noninvasively has been made possible by recent technologic developments. We evaluated a new pulse Doppler ultrasonic unit (Velcom-100, Waters Instruments, Inc) in the Surgical Intensive Care Unit at the University of Michigan Medical Center. Accuracy of this device was determined by comparison of CO results obtained from the Velcom-100 (COV) against those of conventional thermal dilution cardiac output (COT) measurements. Twenty-six postoperative patients were used for this study, ranging in age from 20 to 82 years old. Initial studies prior to in vivo standardization demonstrated a significantly lower result (p = 0.039) for the Velcom-100 with a mean difference of 0.86 L/min (COT-COV). This comparison was significantly improved in subsequent studies following in vivo standardization (COT-COV = 0.02 L/min, p = 0.646). Linear regression analysis showed a significant, positive correlation between the two results (r = 0.82, p less than 0.05) indicating an excellent trending capability for the Velcom-100. Our evaluation found the Velcom-100 to be user friendly, allowing rapid training of ICU technicians and applicability for postoperative monitoring.

Cytogenetic study of four cancers of the prostate.

We cytogenetically studied four cases of adenocarcinoma of the prostate. All tumors were moderately differentiated or well-differentiated, with different degrees of invasion. One tumor with microscopic seminal vesicle invasion and lymph node metastasis (tumor 4) had trisomy 7 as a sole clonal abnormality, suggesting that this is a primary change in some prostatic tumors. Although only normal karyotypes were observed in the other three tumors, several nonclonal changes were evident. Monosomy 9 or deletion of the long arm of 9 was observed in at least one cell in the three tumors without trisomy 7. Furthermore, in one of these tumors (tumor 3, moderately differentiated), several rearrangements (five of 26 cells) were observed, two of which had a common breakpoint at 15q11. Although complex chromosome changes including del(10q) and del(7q) have been described in prostatic tumors, they were not observed in the four tumors studied. This is the first report of a prostate tumor with trisomy 7 as a single clonal chromosome abnormality.

Measurement of elemental nitrogen by chemiluminescence: an evaluation of the Antek nitrogen analyzer system.

Application of indirect calorimetry has aided nutritional support and management in critically ill populations. However, knowledge of resting energy expenditure is only one-half of the nutritional profile. Knowledge of protein losses and requirements are also important. Attainment of positive protein balance is believed to play an important role in wound healing, host defenses, morbidity, and mortality. Previous limitations of the measurement of protein losses (time and cost) have limited its application to the ICU patient. This report describes a relatively new technology which measures elemental nitrogen in biologic samples. We have found this instrument to be fast, accurate, easy to calibrate and use. Its application in the critically ill patient allows us to monitor daily changes in protein losses and balance.

Advances in the diagnosis of urothelial neoplasia.

Urothelial neoplasia is a unique cancer in that is consists of a spectrum of tumors with different biologic behaviors. The most common urothelial neoplasm is the low grade superficial papillary carcinoma or papilloma which may recur numerous times but does not result in significant morbidity or mortality. A variant of the superficial papillary carcinoma, which represents approximately 10% of the tumors, is the noninvasive papillary neoplasm which progresses to a less differentiated invasive transitional cell carcinoma (TCC). Considerable effort has been directed at identifying which of the superficial well differentiated papillary tumors will persist, recur, and progress to invasive cancer. Current approaches to identifying such tumors include cytogenetics, molecular biology, and flow cytometric DNA analysis. In the final group of bladder carcinomas, the high grade invasive neoplasms, evidence suggests that these life-threatening tumors arise de novo without identifiable precursors. Unfortunately, 75% to 90% of invasive TCCs are classified in this group, with the remaining minority progressing from preexisting recurrent superficial papillary carcinomas. Obviously the biologic behavior of these aggressive poorly differentiated tumors is life-threatening, and application of traditional diagnostic procedures and new technologies need to be directed at early diagnosis.

The high incidence of benign testicular tumors.

Of 2,800 testicular procedures performed at our institution between 1965 and 1985, 233 inguinal explorations were done for suspicion of cancer. Malignancy was present in 161 patients but in 72 cases (31 per cent) benign lesions were found. Despite the benign nature of the lesion 51 of these patients (70 per cent) underwent radical orchiectomy. The incidence of benign testicular tumors is much higher than previously suspected and awareness of this condition should lead to increased testicular preservation in selected cases.

Phototherapy of bladder cancer: dose/effect relationships.

Hematoporphyrin derivative photodynamic therapy has very important clinical applicability in the diagnosis and treatment of transitional cell carcinoma of the bladder, but many aspects of the photodynamic process are yet to be elucidated. This paper investigates the role of dihematoporphyrin ether (DHE) concentration, the duration of light exposure, and the initial size of the tumors in the treatment of a transplantable murine transitional cell tumor system. The best results were noted in tumors less than six mm. in diameter when treated with 15 mg./kg. DHE and exposed to 100 to 180 minutes of visible light. Animals with small initial tumor size combined with higher DHE concentration and longer light exposure time were most likely to show tumor response.

Conservative management of epidermoid cyst of testis.

Epidermoid cysts are rare benign tumors of the testicle whose management is controversial. Only 186 cases have been reported, and most were treated with radical orchiectomy. We report 2 cases managed with local excision, and we review the world literature.

Use of occlusion balloon catheter in percutaneous renal stone extraction.

Using an occlusion balloon catheter during percutaneous removal of renal calculi can increase the success of obtaining a nephrostomy as well as enhance the removal of stone fragments.

The synergistic effect of hyperthermia and chemotherapy on murine transitional cell carcinoma.

The in vivo effect of hyperthermia and chemotherapy was studied in a murine transitional cell carcinoma model. Localized hyperthermia (43.5C) of 60 and 90 minutes duration was combined with systemic doxorubicin hydrochloride, cis-platinum, cyclophosphamide or mitomycin to treat tumors implanted into the hind legs of C3H mice. The data were compared to the results obtained from the application of hyperthermia or chemotherapy alone as well as to the natural growth rate of untreated tumors. Untreated tumors grew with an exponential rate and had a doubling time of 4 +/- 1.5 days. Animals bearing such tumors survived for 25 +/- 7 days. When treated with hyperthermia alone, there was no significant reduction in the growth rate and no improvement was noted in the survival time. Treatment with doxorubicin hydrochloride, cyclophosphamide or mitomycin administered alone was likewise not effective. Cis-platinum alone was able to induce a minimal decrease in the growth rate. When the administration of chemotherapy was accompanied by hyperthermia, significant synergistic effect was noted for doxorubicin hydrochloride, cis-platinum and cyclophosphamide (p less than .01); only the mitomycin and hyperthermia combination failed to improve survival and decrease the growth rate. The duration of the hyperthermia exposure influenced the degree of tumor response. Hyperthermia of 90 minutes duration resulted in consistently greater decrease in tumor growth rate with doxorubicin hydrochloride, cis-platinum or cyclophosphamide than 60 minutes of hyperthermia combined with the same agents. These results indicate that local hyperthermia combined with doxorubicin hydrochloride, cis-platinum or cyclophosphamide can induce tumor regression, increase tumor doubling time and improve the survival of the tumor-bearing animal. Only the hyperthermia-mitomycin combination did not result in significant improvement from the baseline values. Thus, hyperthermia combined with selected chemotherapeutic agents can have an adjuvant effect in the treatment of established, implanted mouse bladder tumors.

Pre-transplant urologic investigation and treatment of end stage renal disease.

We investigated 112 patients with end stage renal disease. Clinical evaluations included cystoscopy, cystometry, voiding cystography, bilateral retrograde pyelograms, history and physical examination, and appropriate serum and urinary studies. Of the 112 patients 28 (25 per cent) had significant abnormalities of the urinary tracts. Of the 28 patients 17 had lower tract abnormalities, such as detrusor hyporeflexia, obstructing prostatic hyperplasia and urethral stricture, and 11 had upper tract disease, 9 of whom required a pre-transplant surgical procedure. Included in the group of 9 patients were those with polycystic kidneys, staghorn calculi, renin-related renal hypertension, chronic pyelonephritis and persistent vesicoureteral reflux. None of the azotemic patients had significant morbidity with the timing of the surgical procedures. We believe that eradication of such conditions in the pre-transplant period resulted in a more suitable candidate for renal transplantation. Furthermore, we believe that our finding of 25 per cent abnormalities underscores the need for early urologic evaluation of these patients to ensure their functional capabilities as a recipient.

Probable clonal origin of aldosteronomas versus multicellular origin of parathyroid "adenomas".

Adrenocortical adenomas causing hyperaldosteronism in two women heterozygous at the X chromosome-linked glucose-6-phosphate dehydrogenase (G-6-PD) locus exhibited only one G-6-PD isoenzyme. This finding suggests a clonal development for these benign tumors and contrasts with the multicellular origin of parathyroid adenomas reported in three patients from our institution in 1977 and found subsequently in seven other hyperparathyroid women whose cases are reported here. One of these seven patients had hereditary hyperparathyroidism. In this case each of three glands removed showed both A and B G-6-PD isoenzymes in similar ratios as were found in normal tissues. The multicellular origin of hereditary hyperparathyroidism is compatible with the concept of parathyroid lesions being manifestations of the first genetic event in Knudson's two-mutational-event theory for the initiation of cancer. The multicellular origin of sporadic parathyroid tumors suggest that they are caused by some factors stimulating many cells in the parathyroid glands. The young average age of onset of eight cases of parathyroid cancer from five families with hereditary hyperparathyroidism in the literature is also compatible with Knudson's theory. G-6-PD studies of other aldosteronomas, parathyroid tumors, and other endocrine neoplasms may provide important information about the pathogenesis of these conditions.