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Biomedical subjects

M M Lieber

Publications and source records attributed to M M Lieber.

At least 145 records · Page 8Linked to original sources

Nuclear deoxyribonucleic acid ploidy and serum prostate specific antigen in operable prostatic adenocarcinoma.

A total of 71 patients with prostate carcinoma who underwent radical retropubic prostatectomy had preoperative measurement of serum prostate specific antigen levels and subsequent nuclear deoxyribonucleic acid ploidy analysis of the resected tumors. Prostate specific antigen levels were determined by a commercially available prostate specific antigen radioimmunometric assay (normal range 0 to 4.0 ng./ml.). The paraffin-embedded blocks of the prostate specimens were analyzed by flow cytometry for nuclear deoxyribonucleic acid content using Hedley's technique and propidium iodide staining. A strong association was found between nuclear deoxyribonucleic acid ploidy patterns and preoperative prostate specific antigen values. All patients with tetraploid and aneuploid tumors had elevated preoperative prostate specific antigen values. By contrast, all patients with preoperative antigen values of less than 4 ng./ml. had diploid tumors (p less than 0.0034). Prostate specific antigen levels were proportional to the estimated volume of the primary tumor (p less than 0.0065). However, even after statistical adjustment for tumor volume the preoperative prostate specific antigen value was still significantly and independently correlated with deoxyribonucleic acid ploidy pattern (p less than 0.007). However, only 35% of the patients with diploid tumors had antigen levels within the normal range. Conversely, 65% of the patients with diploid neoplasms had abnormally high antigen levels preoperatively. These results suggest that patients with localized biopsy proved prostate carcinoma and normal preoperative prostate specific antigen values are most likely to have diploid tumors; based on a 95% confidence level, the true proportion of patients with normal prostate specific antigen values who also have a deoxyribonucleic acid diploid tumor is 85 to 100%. Since localized deoxyribonucleic acid diploid tumors are known to be associated with a favorable prognosis for patients with prostate carcinoma treated by radical prostatectomy, a preoperative serum prostate specific antigen level within the normal range may help to predict disease outcome.

Adenocarcinoma↗

Primary adenocarcinoma of the bladder: favorable prognostic significance of deoxyribonucleic acid diploidy measured by flow cytometry.

Flow cytometric nuclear deoxyribonucleic acid ploidy analysis was done successfully on 38 specimens of primary bladder adenocarcinoma treated between 1954 and 1985. Of the specimens 10 (26%) were deoxyribonucleic acid diploid, 8 (21%) were tetraploid and 20 (53%) were aneuploid. Distribution of ploidy patterns between the 14 histological low grade and 24 high grade tumors was similar. Of 38 tumors 35 (92%) showed muscle invasion. One tumor arose in a previously exstrophied bladder, 10 were of urachal origin and 27 arose in an anatomically normal bladder. Of the urachal origin tumors 80% were deoxyribonucleic acid aneuploid. At 5 and 10 years after diagnosis 80 and 70%, respectively, of the patients with diploid tumors were free of disease. By contrast, at 5 and 10 years after treatment only 20 and 12%, respectively, of the patients with nondiploid tumors have not had disease progression (p less than 0.001 log-rank test). None of the 6 patients with diploid, high grade, high stage, muscle invasive tumors had subsequent progression. In contrast, 16 of 17 patients (94%) with high grade, high stage, nondiploid tumors had either local or distant tumor recurrence (p less than 0.0005). Nuclear deoxyribonucleic acid ploidy pattern appears to be the most significant prognostic information currently available to stratify expected prognosis for patients with muscle invasive adenocarcinoma of the bladder. This test probably should be a standard tool in the clinical management of patients with this rare bladder malignancy.

Adenocarcinoma↗

"Benign" metastasizing giant cell tumor: evaluation of nuclear DNA patterns by flow cytometry.

Nuclear deoxyribonucleic acid (DNA) ploidy was determined by flow cytometry for nine histologically benign giant cell tumors that developed systemic metastases and for eight tumors that did not metastasize. Specimens from the primary tumor, local recurrences, and pulmonary metastases were evaluated. No feature of the DNA ploidy pattern was identified to distinguish giant cell tumors that metastasized from those that did not. The mean percentage of diploid (G0/G1 peak, 2C) cells was 81% in the metastasizing group and 80% in the nonmetastasizing group. The DNA ploidy pattern of the primary tumors was not different from that of their metastases. No DNA aneuploid patterns were observed among the benign tumors.

Cell Nucleus↗

Bladder carcinoma presenting with rectal obstruction.

Two patients with bladder carcinoma that caused annular constriction of the rectum are described. A mechanism of local invasion by genitourinary malignancies (bladder and prostate) involves penetration of the rectovesical fascia of Denonvillier and circumferential rectal spread. Treatment of complete or partial obstructing lesions includes surgery, radiotherapy, or chemotherapy (or combination), as well as several new techniques, notably laser destruction and transrectal tumor resection.

Carcinoma, Transitional Cell↗

Flow cytometric DNA analysis of stage I endometrial carcinoma.

Flow cytometric DNA analysis was performed on 203 paraffin-embedded archival specimens obtained from patients with surgical stage I endometrial carcinoma. Primary therapy for those patients (1979-1983) had been definitive extirpation with adjuvant therapy determined by histologic grade, histologic subtype, myometrial invasion, and peritoneal cytologic findings. Diploid DNA patterns were identified in 171 (84%) specimens and nondiploid characteristics were observed in the remaining 32 (25 DNA aneuploid, 7 DNA tetraploid). Although DNA nondiploid specimens accounted for only 16% of all stage I patients, they accounted for 50% of all relapses. Regardless of treatment or other pathologic features, progression-free 5-year Kaplan-Meier survival estimates were 92 and 63% for patients with DNA diploid and DNA non-diploid patterns, respectively (P less than 0.001). Overall 5-year progression-free survival for patients with grade 1 or 2 lesions was 90%; stratification by DNA diploid and DNA nondiploid patterns revealed progression-free survivals of 94 and 64%, respectively (P less than 0.001). Peritoneal cytologic study was positive in seven patients; none of the five with a DNA diploid pattern had a relapse and both with the DNA nondiploid pattern had relapses. These studies suggest that DNA ploidy status may be an objective prognostic determinant for patients with stage I endometrial carcinoma.

DNA, Neoplasm↗

Pattern of failure after radical retropubic prostatectomy for clinically and pathologically localized adenocarcinoma of the prostate: influence of tumor deoxyribonucleic acid ploidy.

From 1966 to 1980, 315 patients underwent bilateral pelvic lymphadenectomy and radical retropubic prostatectomy without adjuvant treatment for clinically and pathologically localized adenocarcinoma of the prostate. Followup was 5 to 21 years, with a median of 8 years. The disease was pathological stage A in 24 patients (8%) and pathological stage B in 291 (92%). A total of 45 patients (14.2%) experienced progression. Over-all, 28 patients (8.9%) suffered local recurrence at a mean of 6.6 years postoperatively (median 5.5 years). Local recurrence was noted as late as 15 years postoperatively. Over-all, systemic progression was observed in 25 patients (8%) after a mean of 4.7 years (median 6 years). Eight patients (2.5%) experienced local and systemic failure. The projected local and systemic failure rates at 15 years were 22% and 15%, respectively. Disease-specific survival at 15 years was 93%, since only 11 patients (3.4%) died of prostate cancer. In an age-matched case control analysis, after all prognostic variables were analyzed (Mayo grade, Gleason score, capsule involvement, number of foci, volume of tumor and deoxyribonucleic acid tumor ploidy), progression was related to nondiploid deoxyribonucleic acid tumor ploidy (p less than 0.0004) as determined by flow cytometry in 63% of the patients who evidenced progression versus 8% of the nonrecurrent group.

Adenocarcinoma↗

Nuclear deoxyribonucleic acid ploidy in squamous cell bladder cancer.

Flow cytometric analysis of nuclear deoxyribonucleic acid content was performed on 76 primary squamous cell bladder carcinomas treated between January 1970 and December 1975. Patients were followed for a median of 10.1 years. Nuclei were extracted from paraffin-embedded archival material and isolated nuclei were stained with propidium iodide. Of the 76 tumors 73 were evaluable by flow cytometry providing high quality deoxyribonucleic acid histograms: 27 (37 per cent) showed a deoxyribonucleic acid diploid or normal pattern, 17 (23 per cent) exhibited a significant increase in the 4C peak (deoxyribonucleic acid tetraploid) and 29 (40 per cent) showed a distinct aneuploid peak. High grade (grades 3 and 4) and high stage (stages T2 to T4) tumors had a significantly higher incidence of abnormal (either tetraploid or aneuploid) deoxyribonucleic acid patterns than low grade (grades 1 and 2) and low stage (stages Tis/Ta/T1) tumors (p less than 0.005). The 5 and 10-year rate free of disease for patients with deoxyribonucleic acid diploid tumors was 67 per cent compared to 22 and 18 per cent, respectively, for patients with tumors showing abnormal ploidy patterns (p less than 0.0005). At 5 and 10 years after diagnosis an estimated 18 per cent of the patients with deoxyribonucleic acid diploid tumors will die of bladder cancer. In contrast, an estimated 53 per cent of the patients with tetraploid tumors and 82 per cent and 86 per cent of those with aneuploid tumors will die of squamous cell bladder carcinoma by 5 and 10 years after diagnosis (p less than 0.0001). These results demonstrate that nuclear deoxyribonucleic ploidy measured by flow cytometry is an important objective prognostic variable for patients with squamous cell carcinoma of the bladder.

Carcinoma, Squamous Cell↗

Stage C prostatic adenocarcinoma: flow cytometric nuclear DNA ploidy analysis.

Flow cytometric nuclear DNA ploidy analysis was used to study pathologic stage C prostatic adenocarcinoma (pT3, N0, M0) in 146 patients who underwent radical retropubic prostatectomy and bilateral pelvic lymphadenectomy between 1967 and 1981. Of these tumors, 46% had a DNA diploid pattern, 47% had a DNA tetraploid pattern, and 7% had a DNA aneuploid pattern. Abnormal ploidy patterns were associated more frequently with histologic high-grade tumors than with low-grade tumors. Considered alone, DNA ploidy pattern showed a strong association with subsequent prognosis. The median interval to progression for tumors with DNA tetraploid and DNA aneuploid patterns was 7.8 and 3.5 years, respectively. For the DNA diploid tumors, only 23% progressed within 18 years, the longest follow-up. At 10 years, only 10% of patients with DNA diploid tumors had died of prostatic cancer, in comparison with 28% of the DNA tetraploid and 36% of the DNA aneuploid groups (P less than 0.01). By analysis of a combination of histologic tumor grade and nuclear DNA ploidy pattern, an even stronger association with prognosis was demonstrated. For the 38 patients with histologic low-grade and DNA diploid tumors, progression-free survival was 92% at 10 years, in comparison with 57% for 23 patients with low-grade DNA nondiploid tumors. Patients with high-grade tumor had a poorer prognosis whether the DNA ploidy pattern was diploid or nondiploid. Nuclear DNA ploidy pattern is an important and independent prognostic variable for patients with pathologic stage C prostatic cancer treated by radical prostatectomy.

Adenocarcinoma↗

Carcinoma of the anal canal and flow cytometric DNA analysis.

Using flow cytometric DNA analysis of paraffin embedded tissue, DNA histograms were successfully obtained from the anal cancers of 117 patients. DNA diploid patterns were given by 82 cancers (70%) and DNA non-diploid patterns by 35 cancers (30%): 15 DNA aneuploid, 20 DNA tetraploid. Well differentiated squamous cell cancers were mainly DNA diploid, while a larger proportion of poorly differentiated and small cell cancers were DNA non-diploid. The large majority of stage A cancers were DNA diploid. A greater proportion of tumours that had invaded through the anal sphincter or had lymph node metastases or distant spread were DNA non-diploid. Prognosis was slightly poorer for patients with DNA non-diploid cancers when compared to patients with DNA diploid tumours (P = 0.08) and significantly poorer for individuals with DNA aneuploid anal cancers (P = 0.037). However, in a multivariate analysis model, the DNA ploidy pattern of an anal cancer was not of independent prognostic significance alongside tumour histology and tumour stage.

Aged↗

Seminal vesicle imaging.

The purpose of this paper is to enhance the understanding of CT, MRI and US images of the seminal vesicles. Accurate interpretation of images requires knowledge of normal anatomy, embryology and pathology. Anatomy and a spectrum of abnormalities are reviewed and discussed. Cases are from an analysis of clinical and surgical files to show the diagnostic features of various cystic diseases of the seminal vesicles. Tissue characteristics of the seminal vesicles on CT, MRI and US images are emphasized.

Adult↗

The relationship of flow cytometric DNA analysis and clinicopathology in small-intestinal carcinoids.

Paraffin-embedded archival tissue samples were used for nuclear deoxyribonucleic acid (DNA) content study by flow cytometry on 56 surgically resected, primary, small-intestinal carcinoid tumors. Sample preparation was carried out using the methods of Hedley and Vindelov. To reduce nuclear aggregation, a procedure of sonication was also performed. Nineteen (34%) cases were DNA diploid, 34 (61%) cases showed significantly increased 4C peak (DNA tetraploid), and only three (5%) cases were DNA aneuploid. Cell cycle phase analysis revealed that carcinoid tumors had significantly higher G2% than those of nontumor control tumors. However, there was no significant correlation between clinical parameters and both DNA ploidy pattern and cell cycle phase analysis. Although the difference in survival between patients with DNA nondiploid tumors and DNA diploid tumors was not significant, all of the patients with DNA aneuploid tumor had poor prognosis followed by death from carcinoid tumor.

Adult↗

Deoxyribonucleic acid ploidy pattern of cardiac myxomas. Another predictor of biologically unusual myxomas.

A group of patients with cardiac myxoma who have a heritable syndrome involving skin myxomas, endocrine tumors, and lentiginosis--the complex of myxomas, spotty pigmentation, and endocrine overactivity--has been described previously. Patients with the complex had cardiac myxomas at an early age (average, 26 years) with frequent multiple myxomas (53%) and recurrent cardiac myxomas (22%); however, no histologic differences were noted when these tumors were compared with sporadic cardiac myxomas. In the present study, deoxyribonucleic acid flow cytometric analyses of 35 cardiac myxoma specimens were correlated with clinical findings (mean duration of follow-up, 13 years). Among 30 patients with sporadic (nonfamilial) cardiac myxoma, 24 (80%) had a normal (deoxyribonucleic acid diploid) ploidy pattern, and six (20%) had an abnormal (deoxyribonucleic acid tetraploid) pattern. Specimens from each of the five patients with the complex had abnormal deoxyribonucleic acid tetraploid patterns (p = 0.002 compared with the sporadic myxoma group). Further, all four patients who had recurrent cardiac myxoma had an abnormal deoxyribonucleic acid ploidy pattern (p = 0.007 compared with patients with nonrecurrent myxomas). Unlike conventional histologic examination, the ploidy pattern of cardiac myxomas seems to be sensitive for detecting biologically unusual tumors, and a deoxyribonucleic acid tetraploid pattern suggests a high risk of recurrence.

Biomarkers, Tumor↗

Flow cytometric analysis of deoxyribonucleic acid ploidy in benign and malignant aldosterone-producing neoplasms of the adrenal gland.

Studies of nuclear deoxyribonucleic acid (DNA) ploidy were performed to determine if ploidy was a marker of a malignant disease or a predictor of prognosis. Paraffin-embedded specimens from 20 benign and six malignant aldosterone-producing neoplasms were examined by flow cytometry. For 17 of the benign aldosteronomas, the DNA histograms were similar to those for samples of normal adrenal cortical parenchyma of adult humans. The three DNA histograms from benign (histologically and clinically) aldosteronomas and all six malignant aldosterone-producing neoplasms were abnormal. Tissue from the adrenal gland from three of the patients with malignant aldosterone-producing tumors exhibited a DNA tetraploid and polyploid pattern; adrenal tissue from three other patients with malignant tumors were classified as having DNA aneuploid histogram patterns. Only patients with DNA aneuploid histogram patterns subsequently died of the disease. Flow cytometry may have an important role prognostically, rather than diagnostically, in the evaluation of aldosterone-producing malignant neoplasms, because the DNA histograms from three benign adenomas were abnormal.

Adenoma↗

Perianal metastasis from a sigmoid carcinoma--objective evidence of a clonal origin. Report of a case.

A case is described in which flow cytometric DNA analysis of a sigmoid cancer and a subsequently diagnosed anal malignancy demonstrated the same DNA aneuploid pattern in both tumors. The ability to show, by this technique of DNA analysis, that an anal malignancy has seeded from a colon cancer could be important for future therapy. This is because the positive identification of such a deposit as a "dropped" metastasis would prevent inappropriately radical surgery.

Adenocarcinoma↗

DNA aneuploidy in solitary colonic adenomas and the future risk of colorectal cancer.

Flow cytometric DNA analysis was performed on the colonic adenomas of 24 patients who had resection of an invasive colorectal carcinoma subsequent to polypectomy. The incidence of DNA aneuploidy among these adenomas was only 13 percent. Thus, simple recognition of colonic adenomas as being DNA diploid or DNA aneuploid is unlikely to be helpful for identifying patients with adenoma who are at high risk for developing a future colorectal carcinoma.

Aneuploidy↗