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Biomedical subjects

G M Farrow

Publications and source records attributed to G M Farrow.

At least 55 records · Page 3Linked to original sources

Flow cytometric DNA histograms of paraffin-embedded pheochromocytomas.

We proposed a new classification of pheochromocytomas according to DNA ploidy patterns. Proliferation index (PI = S% + 4C%) might be an alternative to 4C% which was used as a critical marker of DNA nonaneuploid histograms. The follow-up survey revealed that DNA tetraploid with minimum increase of PI could not rule out the substantial possibility of malignancy and the comparison of DNA diploid histograms disclosed that 22 and 0% showed significant increase of the ratio of 4C% to S% under PI and 4C% criteria, respectively. In conclusion, 4C% was more effective and reliable than PI in order to classify DNA nonaneuploid pheochromocytomas.

Adrenal Gland Neoplasms↗

Stage B prostate adenocarcinoma. Flow cytometric nuclear DNA ploidy analysis.

Over a 16-year period (1966 to 1981), 349 patients underwent radical retropubic prostatectomy for pathologic stage B adenocarcinoma of the prostate. Nuclear DNA content was measured by flow cytometry on available archival material of 283 patients. Two hundred sixty-one patients (92%) had high-quality histograms. The ploidy distribution was as follows: DNA diploid, 177 (68%); DNA tetraploid, 74 (28%); and DNA aneuploid, 10 (4%). The average follow-up was 9.4 years. At the time of follow-up, 53 patients (20%) within the study group had developed tumor progression: 22 local, 23 systemic, and 8 both. The ploidy distribution of the population that developed tumor progression was 27 DNA diploid (51%), 16 DNA tetraploid (30%), and 10 DNA aneuploid (19%). This ploidy distribution is significantly different from that found for the nonprogression group with stage B disease. Overall, 31% of patients with DNA nondiploid tumors had tumors that progressed compared with 15% of patients with DNA diploid tumors. All (100%) DNA aneuploid tumors progressed. The DNA ploidy distribution of all pathologic stage B prostate cancers differs significantly from that found in more advanced stages (C and D1) previously reported for the same time interval. However, the ploidy distribution of stage B tumors that progressed closely resembles that of the stage C and D1 tumors. These results further support the working hypothesis that nuclear DNA content has marked prognostic significance for patients with adenocarcinoma of the prostate. It seems to us that analysis of ploidy by flow or static cytometry will become an essential tool for treating patients with localized prostate cancer.

Adenocarcinoma↗

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↗

Primary malignant lymphoma of the bladder.

We treated 11 patients with primary malignant lymphoma of the bladder. The typical patient is a woman more than 50 years old who presents with urgency and frequency of micturition, and occasionally gross hematuria. Hydronephrosis is present in half of the patients and cystoscopy usually reveals a solid tumor. Partial cystectomy, when feasible, with or without radiotherapy and chemotherapy is the usual treatment modality. When localized to the bladder, malignant lymphoma has an over-all favorable prognosis.

Female↗

In situ hybridization of prostate-specific antigen mRNA in human prostate.

Prostate-specific antigen (PSA) mRNA was detected by in situ hybridization utilizing a 428 base pair [35S]-labelled cDNA probe from the 3' noncoding region of the PSA gene. Thirty six fresh surgical specimens were collected from patients undergoing radical retropubic prostatectomy for carcinoma of the prostate. Quantitative analysis of the levels of PSA mRNA in both the benign and malignant tissues was performed using an IBAS 2000 Image Analysis System. The results of this study demonstrated that there is a significant decrease in the expression of PSA mRNA in the carcinoma tissue when compared to the benign epithelium. The average binding (number of silver grains/1 x 10(4) microns. 2) for 20 specimens of malignant epithelium was 475 +/- 161 and 586 +/- 140 for 16 specimens of benign epithelium (p less than 0.05). Eleven patients had both benign and malignant tissue from the same surgical specimen available for study. From these paired specimens, the PSA mRNA expression was also significantly reduced in the malignant epithelium when compared to the benign epithelium, 445 +/- 162 and 588 +/- 135 respectively (p less than 0.005). The PSA protein was detected using a monoclonal antibody to PSA with an immunohistochemical staining technique. The PSA protein expression paralleled the expression of the PSA mRNA in the majority of the tissue sections. Many of the tumor specimens showed a heterogeneous expression of PSA, whereas all of the benign epithelium had a uniform high level of PSA expression. In conclusion, PSA mRNA and protein are located only within the glandular epithelial tissue, the expression of PSA protein parallels that of the PSA mRNA, and both the PSA protein and PSA mRNA are significantly decreased in the malignant epithelium when compared to benign prostatic epithelium.

Adenocarcinoma↗

Clinical course of an incompletely removed cavernous hemangioma of the orbit.

Cavernous hemangioma is a frequent tumor of the orbit in adults. Its complete removal results in dramatic relief of proptosis. The clinical course of an incompletely removed cavernous hemangioma is seldom recorded in the ophthalmic literature. The authors report the behavior of such a tumor that was observed during an 18-year period. Serial computed tomography (CT) documented a long period of slow growth, followed by a shorter interval of arrest, with eventual involution of tumor and relief of proptosis. No treatment was administered during observation.

Adult↗

Urine cytology in the detection of bladder cancer: a critical approach.

Bladder cancer is composed of a group of tumors heterogeneous with respect to configuration, degree of differentiation, and biological course. Lethal and nonlethal forms of the disease exist. The nonlethal forms of cancer are generally well differentiated and not readily detected by voided urine cytology. The lethal form of cancer is accurately detected by voided urine cytology in symptomatic patients, but current evidence indicates a very short preclinical phase for most cases. A screening program should concentrate on detection of the lethal form of bladder cancer.

Humans↗

Correlation of prostate-specific acid phosphatase and prostate-specific antigen immunocytochemistry with survival in prostate carcinoma.

Prostate-specific acid phosphatase, a secretory product of prostatic cells, may be a secondary product of the interaction of hormones with their receptor proteins. In this study we have examined two independent patient populations to see whether the intensity or extent of prostate-specific acid phosphatase and/or prostate-specific antigen staining correlated with survival and hormonal manipulation. One population of 24 patients was selected from patients undergoing surgical resection for adenocarcinoma Stage B or C at the Mayo Clinic. The second population of 123 patients was obtained from Radiation Therapy Oncology Group Protocols 75-06 and 77-06. Tissue from both populations was analyzed. In both populations, the intensity of prostate-specific acid phosphatase staining correlated with survival in a statistically significant manner. Staining with prostate-specific antigen was present in greater than 90% of specimens; data was therefore not analyzed. In those patients who subsequently relapsed and were subjected to hormonal manipulation, there appeared to be a higher likelihood of response to hormones with intense prostate-specific acid phosphatase staining.

Acid Phosphatase↗

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↗

Amyloidosis of the urethra.

Primary, localized amyloidosis of the urethra is rare. The patient usually presents with hematuria and the appearance of urethral carcinoma. However, the disease is benign and it is treated effectively with local removal. We report our experience with 5 cases.

Adult↗

Incidental adenocarcinoma after open prostatic adenectomy.

Adenocarcinoma of the prostate occasionally is discovered incidentally in the enucleated gland at open prostatic adenectomy for benign disease. Among 468 men who underwent open prostatic adenectomy, unsuspected adenocarcinoma of the prostate was found on pathological examination in 28 (6.0 per cent). The tumors were stage A1 in 14 patients and stage A2 in 14. Careful tissue review resulted in reassigning 5 cases from stage A1 to stage A2. At a mean followup of 10.6 years disease progression had occurred in 4 patients with stage A2 disease. When stage A adenocarcinoma is discovered after open prostatectomy we recommend careful review of the surgical specimen for accurate staging, and adjuvant therapy for all patients with stage A2 disease an for younger patients (less than 65 years old) with stage A1 disease who have favorable life expectancies.

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↗

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↗