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Biomedical subjects

M M Lieber

Publications and source records attributed to M M Lieber.

At least 19 recordsLinked to original sources
PubMed1992

Stage D1 prostate cancer treated by radical prostatectomy and adjuvant hormonal treatment. Evidence for favorable survival in patients with DNA diploid tumors.

BACKGROUND: Stage D1 disease is found in at least every sixth patient undergoing bilateral pelvic lymphadenectomy and radical retropubic prostatectomy (RRP) for clinically localized prostate cancer (PC). Previous recommendations for monotherapy using surgery, radiation, or systemic therapy alone for Stage D1 disease have usually been associated with a poor outcome in regard to progression and survival. Unlike other pathologic stages, D1 disease treated with RRP is mainly related to DNA ploidy pattern in regard to all end points (progression and survival) and immediate adjuvant hormonal treatment (AHT) rather than to the usual pathologic variables, including the number of positive nodes. METHODS: Complete DNA ploidy information was available in 370 patients with Stage D1 disease (age range, 40-77 years; mean, 64 years) undergoing RRP with or without AHT with a follow-up of up to 22 years (mean, 5 years). RESULTS: Overall, 80% of all DNA ploidy classes (diploid, 37%; tetraploid, 46%; and aneuploid, 17%) had AHT that highly significantly delayed progression for diploid (P less than 0.0001) more than tetraploid (P less than 0.0001) and more than aneuploid (P less than 0.0001) tumors. Significant prolongation of the disease-free interval might have improved the quality of life for tetraploid and aneuploid patients. Survival (crude and cause-specific) was significantly (P = 0.02) improved only for diploid patients who received AHT but not for tetraploid and aneuploid patients. This was due to the significantly accelerated death rate after progression in those patients with early AHT for tetraploid and aneuploid (but not diploid) tumors. Delayed (on progression only) AHT resulted in high progression rates for all DNA ploidy classes (aneuploid greater than tetraploid greater than diploid); e.g., 21 of 30 diploid patients progressed and 6 patients died from disease at a median of 31.5 months in spite of immediate hormone treatment on progression. RRP and AHT for patients with Stage D1 disease resulted in a highly significant delay in overall progression (76% at 10 years) and excellent local control, depending on DNA ploidy pattern (diploid greater than tetraploid greater than aneuploid) compared with a treatment regimen without AHT (24% overall nonprogression); only 20% of all patients with AHT are projected to die of disease at 10 years. Disease in diploid patients (37%) treated with AHT rarely progressed and those patients are unlikely to die of disease in 10 years or less; delayed (on progression) hormone treatment for diploid patients seemed ineffective. Inclusion of values for prostate specific antigen led to a higher failure rate on progression, and this is dependent on DNA ploidy class (diploid greater than tetraploid greater than aneuploid). CONCLUSION: Only patients with nondiploid tumors should be entered into prospective studies using innovative adjuvant treatment protocols to improve survival.

Adult↗
PubMed1992

The clinical significance of nuclear DNA ploidy pattern in 184 patients with pheochromocytoma.

Flow cytometric nuclear DNA analysis was performed on paraffin-embedded tissue samples taken from 184 patients with pheochromocytoma and paraganglioma treated between 1960 and 1987. The Hedley technique was used for measurement of nuclear DNA content. Thirty-five percent of the tumors were DNA diploid, 33% showed a DNA tetraploid pattern, and 32% had DNA aneuploid pattern. Familial pheochromocytoma and associated endocrine or neoplastic disorders were more common among patients with DNA nondiploid tumors. Eighty-four percent of the tumors that invaded blood vessels and all patients with regional or distant metastases had tumors classified as DNA tetraploid or DNA aneuploid. Of 22 patients who had disease progression, 21 (95%) had tumors with abnormal DNA ploidy pattern (P less than 0.001). All 12 patients who died of cancer-related disease had abnormal DNA ploidy; none of the patients with DNA diploid tumor (n = 64) have died of pheochromocytoma (P less than 0.01). These results suggest that nuclear DNA ploidy pattern is an important and independent prognostic variable for patients with pheochromocytoma and paraganglioma.

Adrenal Gland Neoplasms↗
PubMed1992

DNA ploidy: early malignant lesions.

The nuclear DNA content of prostate cancer specimens, both needle biopsies and aspiration biopsy specimens as well as transurethral resection (TUR) chips and radical prostatectomy specimens, can now be reliably measured by standardized methods of flow and static image cytometry. For prostate carcinomas of every clinical stage (A1-D2), DNA diploid tumors have a better prognosis than tumors of a similar stage and grade which are non-diploid. Of particular importance to this symposium is the fact that DNA diploid stage D1 and D2 tumors treated early by androgen deprivation generally have a remarkably good prognosis. In contrast, those patients with DNA non-diploid tumors progress early despite androgen deprivation. Such a result suggests that DNA ploidy can be used to identify prostate cancers which are potentially sensitive to hormonal manipulation. Additional investigations from several groups indicate that early stage prostate malignant lesions, for example stages A1, A2, B1, and B2, are generally DNA diploid (about 75%). Swedish data suggest a steady progression of prostate cancer from early diploid to tetraploid, to non-tetraploid aneuploid, to multiple stemline aneuploid tumors with time and advancing stage. Taken together, these data suggest that the earliest detectable prostate carcinomas should be overwhelmingly DNA diploid. A large majority of these patients with early tumors should be candidates for "chemoprevention" by pharmacologic methods which reduce the effective androgen stimulation of prostate tumor cells.

Androgens↗
PubMed1992

Chemoprevention of prostate cancer: guidelines for possible intervention strategies.

The "natural history" of prostate cancer may bedevil the development of guidelines for chemoprevention interventions. Can strategies be designed to direct agents to those lesions which have the potential to develop localized extension that may become symptomatic or metastatic disease? Of necessity our interventions will focus on the identification and quantification of appropriate biomarkers as intermediate endpoints, although no reliable endpoints for prostate cancer have yet been identified. The reduction of prostate cancer incidence may be the ultimate objective, but a decrease in the progression of microfocal or "latent" cancer may well be just as effective as prevention when the age of the target population and competing causes of death are taken into account. Early intervention strategies must focus on the analysis of the interactions of the chosen chemopreventive agents upon precancerous and cancerous cellular dynamics in the prostate. Whether the requirements of such molecular epidemiology necessitate a more deliberate strategy of Phase II studies or a high risk-high gain strategy of a broad Phase III study is open to debate. Factorial designs for proposed randomized chemoprevention trials may be desirable to test multiple chemopreventive agents simultaneously, provided knowledge of the biochemical synergism of the agents is solid. Stratification of study participants by degree of risk will ameliorate concerns regarding the precision targeting of lesions at different stages in the precancer/cancer continuum.

Androstenes↗
PubMed1992

Prognostic profile for patients with pheochromocytoma derived from clinical and pathological factors and DNA ploidy pattern.

Eighty-eight patients with pheochromocytoma and paraganglioma treated over a 28 year period (1960-1987) were studied. Based on clinical course, they were divided into three prognostic groups: benign (n = 57); multiple (n = 12); and metastatic (n = 19). Using clinical data, histopathologic findings, and tumor nuclear DNA content a prognostic profile for each group was constructed. The following variables were studied: age, familial pheochromocytoma, associated endocrine or neoplastic disorders, number and location of the lesion at diagnosis, size of the tumor, and the nuclear DNA ploidy pattern. Of these prognostic factors the most significant to predict a future malignant clinical course were large size and local tumor extension at time of surgery. Family history of pheochromocytoma, associated endocrine disorders, and young age at presentation predicted multiplicity. Old age, absence of familial pheochromocytoma or related endocrine disorders and DNA diploid tumors seem to be favorable findings. Using these variables in combination may be helpful for early identification of patients with malignant, multiple, or benign pheochromocytoma and paraganglioma.

Adrenal Gland Neoplasms↗
PubMed1992

DNA ploidy of ovarian dysgerminomas: correlation with clinical outcome.

Abnormal nuclear DNA content, as determined by flow cytometry, when combined with conventional prognostic variables such as tumor grade or stage at diagnosis, appears to identify patients who are at increased risk for recurrence of disease. The DNA content of ovarian dysgerminoma, a tumor that is homologous to testicular seminoma and is found in young women of childbearing age, was studied to determine if there is a correlation between DNA content and outcome. Such information would be useful in selecting treatment regimens and making possible the preservation of childbearing potential in women who are likely to have a good outcome. The specimens from 23 cases of ovarian dysgerminoma seen at our institution between 1950 and 1985 were analyzed by DNA flow cytometry. Five of the tumors were diploid (21%) and nineteen were nondiploid (79%). Patient outcome was not predicted any better by nuclear DNA content than by conventional prognostic variables.

Adult↗
PubMed1992

Validation of a new quality of life questionnaire for benign prostatic hyperplasia.

In planning a longitudinal study to characterize the natural history of benign prostatic hyperplasia (BPH), we validated a new disease-specific quality of life questionnaire in a pilot study. We studied 110 men in Rochester, Minnesota who spanned the severity of BPH, from men with no known BPH to men who underwent surgery for this condition. Baseline data were obtained on all men, and the 30 who underwent prostatectomy were re-interviewed to test responsiveness. Reproducibility was examined on the pre-post responses (10 weeks apart) of the 37 men with BPH who did not undergo prostatectomy. Six of twelve question domains were retained in the final questionnaire on the basis of their responsiveness to change, reproducibility, internal consistency, and validity. These were: urinary symptoms, degree of bother due to urinary symptoms, BPH-specific interference with activities, general psychological well-being, worries and concerns, and sexual satisfaction. Most of the more generic measures were deleted.

Adult↗
PubMed1992

Nuclear deoxyribonucleic acid content measured by static cytometry: important prognostic association for patients with clinically localized prostate carcinoma treated by external beam radiotherapy.

To determine if relative nuclear deoxyribonucleic acid (DNA) content is an important prognostic parameter for patients with clinically localized prostate carcinoma treated by external beam radiotherapy, we performed static DNA cytometry on archival paraffin embedded prostate needle biopsy specimens obtained before treatment. DNA content was measured with the Zeiss IBAS 2000 Image Analyzer and the Feulgen staining method. Tumor samples from 65 patients with clinically localized carcinoma of the prostate treated with at least 6,000 cGy. from 1974 to 1980 were studied. Patients and tumors were divided into 2 groups: group 1 - 31 patients with relative DNA content less than 1.5 times normal and group 2 - 34 patients with relative DNA content greater than 1.5 times normal. The prostate cancer nonprogression rate at 10 years was 64% for group 1 and 11% for group 2. Prostate cancer cause specific survival at 10 years was 73% for group 1 and 20% for group 2. These differences are highly significant (p less than 0.0001). By contrast, stratification and analysis according to tumor clinical stage, Mayo histological nuclear grade or Gleason score proved not to be as significant. Cox multivariate analysis also identified DNA content as the most important independent variable for cancer specific survival and progression. Nuclear DNA content measured by static cytometry appears useful in identifying those patients with clinically localized prostate carcinoma who may have a favorable probability of long-term disease control by external beam radiotherapy.

Aged↗
PubMed1992

Hormonal treatment at time of radical retropubic prostatectomy for stage D1 prostate cancer: results of long-term followup.

In this long-term study with a median followup of greater than 10 years 62 patients who underwent bilateral pelvic lymphadenectomy and radical retropubic prostatectomy for stage D1 adenocarcinoma of the prostate were subdivided with respect to nuclear deoxyribonucleic acid ploidy status of the primary cancer and according to whether they received adjuvant early antiandrogen therapy. Patients with diploid cancers who underwent the operation and received adjuvant early endocrine therapy did significantly better than a similar group without early endocrine therapy with respect to disease-free survival (p less than 0.001) and survival from prostate cancer death (p = 0.03). Among patients with nondiploid tumors early endocrine therapy was of some benefit for disease-free survival (p = 0.06) but not for prostate cancer death (p = 0.46).

Adenocarcinoma↗
PubMed1992

A prospective randomized comparison of epidural infusion of fentanyl and intravenous administration of morphine by patient-controlled analgesia after radical retropubic prostatectomy.

In a prospective, randomized study, continuous infusion of epidural fentanyl citrate (group E) was compared with patient-controlled intravenously administered morphine sulfate (group P) for analgesia in 66 men after radical retropubic prostatectomy. Although both methods provided satisfactory analgesia, the mean comfort level scores were lower (that is, greater comfort) in group E than in group P at all observation times. The difference in mean resting comfort level scores between groups E and P was statistically significant (P < or = 0.05) at 9 of the 11 observation times. In addition, significant differences in comfort level scores were noted at 8 of the 11 observation times during deep breathing, 5 of 11 during coughing, and 3 of 9 during ambulation. Maximal and minimal comfort level scores recorded by each patient during the course of the study were significantly lower (that is, less pain) in group E than in group P for all four categories of activity. The percentage of patients who reported no pain was significantly higher in group E than in group P at 9 of 11 observation times during resting and 5 of 11 observation times during deep breathing. No significant differences were noted in side effect profiles or duration of hospital stay. In summary, when two effective methods of analgesia used after radical retropubic prostatectomy were compared prospectively, patients who received epidural infusion of fentanyl were more comfortable than those with patient-controlled intravenous administration of morphine, as evidenced by lower mean, maximal, and minimal comfort level scores and a greater proportion of patients with complete relief of pain.

Aged↗
PubMed1992

Effect of external beam radiotherapy on prostatic carcinoma DNA content as measured by static image cytometry.

Static image cytometry was used to study the effect of radiotherapy on the DNA content of prostatic carcinoma. Feulgen-stained specimens from 50 patients before and after radiotherapy were examined. The DNA index increased significantly after treatment (p less than 0.03), and it occurred equally in those with low (less than 1.5) and high (greater than or equal to 1.5) indices. The level of the initial DNA index was significantly related to the rate of symptomatic progression (p less than 0.05). The initial change in and final DNA indices were not related to survival however. There was a significant increase in Gleason score (p = 0.001) and histological grade (p = 0.01) after irradiation and, when taken individually, the degree of change was related to survival in both, p = 0.05 and 0.004, respectively. As Gleason score, Mayo grade and clinical stage were not independent variables; none of them was related to survival when corrected for the other factors. Thus, DNA content or ploidy, as well as Mayo grade and Gleason score, increases in recurrent tumor after radiotherapy. This may be of importance when considering what treatment to use and how intensively the patients should be followed up.

Actuarial Analysis↗
PubMed1992

The prognostic significance of DNA ploidy pattern in transitional cell cancer of the renal pelvis and ureter: continuing follow-up.

Among 190 patients operated on for transitional cell cancer of the renal pelvis and/or ureter from 1976 to 1990, 95 had their tumor studied by flow cytometry. Of these, the prognostic significance of the DNA ploidy pattern with respect to the standard pathologic features was assessed in a retrospective analysis, where survival information were updated to October 1991 and the mean follow-up of patients exceeded 5.5 years (longest follow-up: 15.5 years). Five and ten-year survival probabilities for the whole group were, respectively, 65.5 and 51%. Patients with a diploid tumor had significantly better survival rates than patients with tetraploid/aneuploid cancer (p less than 0.00001). The impact of the DNA ploidy on survival was confirmed by a multivariate analysis of prognostic factors, where only tumor grade (p less than 0.0001), tumor stage (p less than 0.0001), number of neoplastic foci (p = 0.022) and nuclear DNA pattern (p less than 0.068) had a significant influence on survival. In the group of patients with low-stage (pTa-pT1) and low-grade (G1-G2) transitional cell cancer of the upper urinary tract, the DNA analysis was unable to identify any subset of patients at higher risk for disease progression.

Carcinoma, Transitional Cell↗
PubMed1991

Treatment of primary squamous cell carcinoma of the upper urinary tract.

Forty-six patients with primary squamous cell carcinoma of the upper urinary tract treated over a 44-year period were studied. The lack of characteristic presentation caused delay in diagnosis. Associated urinary calculi were found in only five (11%) of the patients. Almost all of the tumors were histologically high grade; at surgery, 84% of the tumors were locally advanced or metastatic. Prognosis is poor independent of treatment; the overall 24-month survival rate was 22%. Comparison with a previous study of renal pelvic transitional cell carcinoma indicates that these two forms of urothelial neoplasm are biologically different.

Adult↗
PubMed1991

Urinary symptom and quality of life questions indicative of obstructive benign prostatic hyperplasia. Results of a pilot study.

In a pilot study of a urinary symptom and health-related quality-of-life questionnaire for benign prostatic hyperplasia (BPH), responses from 64 Mayo Clinic patients with cystoscopic evidence of obstructive BPH were compared with those of 14 men with no cystoscopic evidence of BPH and a community sample of 64 comparably aged men with no medical history of prostate enlargement. Questions which best discriminated between the groups were those dealing with urinary symptom frequency, bother due to urinary symptoms, and worry and concern about urinary problems. The results suggest that urinary-symptom-bother and worry due to urinary symptoms may be important additions to the more usual questions asked about urinary frequency in the identification of men with BPH. These findings are preliminary, however, and will be verified in an ongoing natural history study of BPH.

Humans↗
PubMed1991

Adenocarcinoma of the prostate involving 2 cell types (prostate specific antigen producing and carcinoembryonic antigen producing) with selective metastatic spread.

Of 3 patients with clinically localized adenocarcinoma of the prostate 2 were treated by radical prostatectomy and 1 was treated with radiation therapy. Serum prostate specific antigen (PSA) values were elevated before therapy. After treatment the PSA levels were decreased to zero. All 3 patients later had evidence of metastatic tumor spread to the liver with elevation of serum carcinoembryonic antigen but not PSA. Immunohistochemical staining of the 2 primary tumors from the prostatectomy specimens identified 2 cell clones, one immunoreactive to PSA and prostatic acid phosphatase (PAP) and nonimmunoreactive to carcinoembryonic antigen, and the other immunoreactive to carcinoembryonic antigen but not PSA or PAP. Biopsy of a hepatic metastasis in 2 patients confirmed anaplastic carcinoma of the carcinoembryonic antigen-producing cell type. Immunohistochemical staining of a lymph node metastasis identified the PSA-producing cell type only. Such results suggest selective metastatic spread of each cell type to its own organ tropic site. Occasional carcinoembryonic antigen-producing prostate cancers may metastasize to the liver. Serum carcinoembryonic antigen measurements occasionally may be useful in the management of certain prostate adenocarcinoma patients.

Adenocarcinoma↗
PubMed1991

Transitional cell carcinoma of the upper urinary tract: evaluation of prognostic factors by histopathology and flow cytometric analysis.

Prognostic factors in transitional cell carcinoma of the upper urinary tract were assessed with histopathological examination and flow cytometric analysis in a series of 127 patients operated upon between 1976 and 1988. In particular, we evaluated the usefulness of flow cytometry to identify patients who require adjuvant treatment among those with low grade and low stage disease (51% in this series). A multivariate analysis was done on 92 cases, considering patient age and sex, stage, grade and number of lesions (unifocal versus multifocal), site (renal pelvis versus ureter), presence of vesical tumors, recurrences along the urinary tract or in the bladder, type of operation and nuclear deoxyribonucleic acid (DNA) ploidy (diploid versus tetraploid/aneuploid tumors). Only the stage (p = 0.001), grade (p = 0.001) and, to a lesser extent, the DNA pattern (p = 0.031), as well as the number of lesions (p = 0.061) were determinant for prognosis. In regard to the subgroup of 41 patients with grade 2 or less, stage P1 or less tumors, no significant difference in survival was demonstrated between diploid and nondiploid tumor patients. However, 7 of 10 patients from the latter group are still under observation. Therefore, our conclusions may have to be modified in the future.

Adult↗
PubMed1991

Congenital cystic disease of the seminal vesicle.

Thirteen cases of congenital seminal vesicle cysts with pathologic correlation were diagnosed between 1970 and 1988. Twelve of the 13 patients had ipsilateral renal anomalies. Intravenous urography, performed in 11 of the 13 patients, demonstrated associated renal anomalies. Computed tomography, performed in nine of the 13 patients, demonstrated associated renal anomalies and displayed the cystic seminal vesicles. Transabdominal or endorectal ultrasonography, performed in eight patients, allowed characterization of the seminal vesicle masses as cystic. Magnetic resonance imaging, performed in three of the 13 patients, accurately demonstrated dilated ejaculatory ducts into which ectopic ureters inserted. The fluid in the seminal vesicle cysts had an increased signal intensity on T1- and T2-weighted sequences. Seminal vesiculographic study demonstrated anomalous communications with the seminal tract. Cystic disease of the seminal vesicles can be either congenital or acquired; congenital cysts are associated with anomalies of the ipsilateral mesonephric duct.

Adult↗