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Biomedical subjects

F S Freiha

Publications and source records attributed to F S Freiha.

At least 37 records · Page 2Linked to original sources

Incidentally discovered solid renal masses: what are they?

In 36 of 99 consecutive patients operated on for the presumptive diagnosis of renal carcinoma the tumour was discovered accidentally during investigations for a variety of complaints. CT and ultrasound scans were responsible for discovery of the tumour in 24 of the 36 patients. Renal carcinoma accounted for 92% of incidentally discovered solid renal masses. Of 33 incidentally diagnosed renal carcinomas 27 were stage 1. An incidentally discovered solid renal mass should be regarded as a low stage renal carcinoma until proven otherwise.

Aged↗

Pathologic parameters and flow cytometric ploidy analysis in predicting recurrence in carcinoma of the prostate.

Recurrence of prostate cancer following radical prostatectomy is determined by the extent of local disease. Tumor volume and grade have improved our ability to predict extraprostatic extension, but tumors of intermediate volume and grade vary in their biologic behavior. To assess the prognostic significance of DNA ploidy, we performed flow cytometry in 85 patients with prostate cancer volumes > 4 cm3. Post-radical prostatectomy serum prostate-specific antigen was used to prove recurrence of cancer. Mean follow-up was 35 months (median 31 months). 26 patients (30%) had diploid histograms, 55 (65%) non-diploid histograms. In 4 cases (5%) the histograms were uninterpretable. Tumor volume and percent of Gleason grades 4 or 5 separated the recurrent from nonrecurrent groups in a highly significant manner (p < 0.001). When tested alone, ploidy had no ability to predict recurrence (p = 0.26). However, in a subset of patients with 4-8 cm3 of cancer with < 30% Gleason grade 4 or 5 tumor, ploidy conferred significant additional prognostic information (p < 0.005).

DNA, Neoplasm↗

[Epidemiologic observations on prostate cancer based on tumor volumes].

Using the SEER Program of the NCI, and the U.S. total mortality rates, we calculated the probability at birth of being diagnosed with prostate cancer within one's lifetime to be 8.8%, and we subtracted the microscopic stage A cancers too small to ever be of clinical significance which gave a final probability of 8%. Prostates were examined in 139 consecutive, unselected cystoprostatectomies from patients with bladder cancers who were unknown to have prostate cancer. Prostate cancer was found in 55 patients (40%); the volume of the largest cancer in each of these 55 prostates was determined by histologic morphometry. We identified the 8% of these 139 cystoprostatectomies with the largest volume of prostate cancer. The largest 11 of the 55 cancers represented 7.9% of the 139 cystoprostatectomies. These cancers ranged in volume from 0.5 cc to 6.1 cc, representing only 20% of all patients with prostate cancer. Thus, if one accepts the strong evidence that cancer progression is proportional to cancer volume, we conclude that prostate cancers larger than 0.5 cc appear to correspond to the 8% of men who will be diagnosed with a clinically significant carcinoma, as derived from SEER data. Conversely, those 80% of prostate cancers under 0.5 cc are probably not destined to reach clinically significant size in view of the very long doubling time of this cancer.

Adult↗

Multiple cancers in the prostate. Morphologic features of clinically recognized versus incidental tumors.

Multiple independent tumors were identified in specimens from 117 of 234 prostatectomies for clinical adenocarcinoma; there were 266 incidental cancers in these 117 prostates. The clinically detected carcinoma was the largest (or only) tumor in all 202 Stage B cases. However, among 32 Stage A cases (detection by transurethral resection), there were 8 prostates in which an incidental tumor was larger than the clinically manifest cancer. These were all small tumors except for two incidental cancers with a volume greater than 2cm3; roughly 80% of incidental carcinomas were smaller than 0.5 cm3, whereas fewer than 20% of manifest tumors were smaller than 0.5 cm3. Comparison with a series of cancers found incidentally at cystoprostatectomy for bladder cancer showed the same volume distribution as incidental (smaller) carcinomas in patients with prostate cancer. This distribution was thought to reflect the volume distribution of prostate cancer in the general population older than 50 years of age. It was concluded that additional incidental tumors are common in patients with prostate cancer, but their sum of volumes is seldom as large as the clinical cancer volume.

Adenocarcinoma↗

Morphologic analysis of surgical margins with positive findings in prostatectomy for adenocarcinoma of the prostate.

Apical invasion and positive apical margins were assessed in 165 consecutive radical prostatectomies. Apical invasion, defined as cancer in the distal 8 mm of the prostate, was evident in more than 80% of the cases, and apical margins occurred in 16% of the specimens with apical Clinical judgement was not effective in predicting apical cancer. Frequency of apical margins increased in proportion to greater cancer volume, from 9.8% in cancers smaller than 4 cc to 30.7% in cancers larger than 12 cc. However, most positive margins in the group with cancers smaller than 4 cc were caused by inadvertent incision into the prostate during the operation, whereas the vast majority of apical margins in cancers larger than 4 cc were caused by capsule penetration of the tumor. Although margins associated with capsule penetration occurred characteristically in the posterior (rectal) portion of the apex, margins caused by incision into the prostate were distributed over the entire apical surface of the gland. Positive margins at the urethral stump were quite uncommon (occurring in four cases). These findings suggest that modifications of surgical technique might reduce the frequency of this complication.

Adenocarcinoma↗

Impact of radical prostatectomy on the characteristics of bladder and urethra.

A prospective study was done to evaluate the long-term effects of radical prostatectomy on the function of the bladder in filling and voiding. Preoperative urodynamic studies were done on 29 patients with a mean age of 62.9 +/- 5.2 years. The preoperative results show that 16 of the 29 patients demonstrated detrusor instability with maximum contractile pressures of 59 +/- 28 cm. water. Followup urodynamic assessment was done in 13 of these patients 22.9 +/- 1.1 months after surgery. Postoperatively, the maximum detrusor instability pressure did not decrease significantly (49 +/- 17 cm. water). Comparison of the operative and postoperative urodynamic characteristics of bladder filling shows that radical prostatectomy produced no significant change in the filling characteristics of the bladder in terms of bladder capacity, or volume at which sensations of fullness or urgency are reported. Voiding pressure-flow studies show a significant increase in maximum flow rate (8 +/- 1 to 13 +/- 2 ml., per second, p = 0.007), and significant decreases in maximum detrusor pressure (61 +/- 5.4 to 39 +/- 4 cm. water, p = 0.002), urethral opening pressure (45 +/- 7 to 25 +/- 4 cm. water, p = 0.004) and residual volume (150 +/- 37 to 62 +/- 43 ml., p = 0.019). Urethral profile measurements show that there was no significant change in either the maximum urethral closure pressure (94 +/- 9 to 83 +/- 9 cm. water) or external sphincter length (3.6 +/- 0.8 to 3.2 +/- 0.8 cm.). Preoperatively, the bladder neck pressures were 25 +/- 4.4 cm. water and were abolished after prostatectomy, indicating that the decrease in obstructive characteristics is due to removal of the prostate.

Aged↗

Transitional cell carcinoma of the prostate in patients undergoing radical cystoprostatectomy.

To assess the impact of prostatic involvement with transitional cell carcinoma we reviewed the clinical outcome of 49 patients with transitional cell carcinoma of the prostate. In addition, 115 step-sectioned cystoprostatectomy specimens removed for bladder transitional cell carcinoma were studied to determine the true incidence of secondary prostatic involvement by transitional cell carcinoma. Specimens from 300 prostates removed for prostatic adenocarcinoma also were reviewed to investigate the presence of incidental transitional cell carcinoma arising within the prostate. Transitional cell carcinoma was found in 29% of the step-sectioned specimens and in none of the radical prostatectomy specimens. The presence of prostatic invasion either into the stroma or involving prostatic ducts and acini only had no adverse effect on outcome. Lymph node status and bladder stage, and not prostatic invasion were the determining factors of survival. The presence of seminal vesicle involvement or prostatic stromal invasion appeared to predict for lymph node involvement. With a mean followup of more than 3 years 75% of our patients who had negative lymph nodes and low stage bladder lesions are alive without evidence of disease. In our series prostatic involvement by transitional cell carcinoma did not impact on survival when patients were treated aggressively with radical cystoprostatectomy.

Adult↗

The predictive significance of substaging stage A prostate cancer (A1 versus A2) for volume and grade of total cancer in the prostate.

Morphometric analysis was performed on 44 radical prostatectomy specimens for clinical stages A1 and A2 carcinoma of the prostate. The majority of stage A cancers (86%) were located in the transition zone of the prostate, while only 14% arose in the peripheral zone. The subclassification into stages A1 and A2 based on the percentage of cancer in the transurethral resection chips did not reliably distinguish those cancers of high volume (transurethral resection plus residual). All 6 cases with Gleason grade 4 elements in the transurethral resection chips had relatively high volume cancer. In 32 of the 44 cases (73%) unsuspected cancers unrelated to the tumor detected at transurethral resection were found in the radical prostatectomy specimen. Of these cancers 87% were nontransition zone tumors. Eight unsuspected cancers were larger than the stage A cancer but only 2 of them were larger than 1 cc. Post-resection serum prostate specific antigen (PSA) levels were elevated with increasing total residual cancer volume in the radical specimen. In 19 of 20 cases with a PSA of greater than 2.5 ng./ml. the total residual cancer volume was more than 0.9 cc, while in 7 of 8 with a PSA of less than 1 ng./ml. total residual tumor volume was lower than 0.4 cc.

Adult↗

[Systematic morphometry of radical prostatectomy samples. A guideline for general practice].

The predictive value of quantitated tumor volume for the prognosis of the individual patient with prostate cancer has been established in analysis of more than 500 radical prostatectomy specimens at Stanford Medical Center. The Stanford technique for detailed tissue sectioning involves considerable time and expense plus computer planimetry. Therefore we have developed two simplified protocols which are suitable to routine diagnostic pathology. Histologic slides of 145 radical prostatectomy specimens, as evaluated by the Stanford technique, were reviewed and a selection of slides was made in a systematic fashion according to two protocols ("bilateral" and "parasagittal"). Tumor volume was estimated manually from this reduced sample of slides by comparing cancer areas to a millimeter grid. The bilateral protocol used an average of 11.7 slides per case (range 8-20), the parasagittal protocol used an average of 8.8 slides per case (range 6-15) versus an average of 26.2 slides per case (range 16-67) by the original Stanford technique. Volume estimates were within +/- 20% of true (computer) volume in 96% and 89% of cases, respectively. A simplified tissue sampling technique can yield accurate cancer volume determinations in radical prostatectomy specimens with reduced time and expense.

Histological Techniques↗

Mucinous differentiation in prostatic adenocarcinoma.

Morphologic and histochemical analysis was performed on 33 carcinomas with mucin-secreting areas that were identified among 100 carcinomas from radical prostatectomy specimens. The most common mucin-secreting pattern was Gleason grade 3, which usually showed distinctive luminal distention. The "colloid carcinoma" pattern with mucinous lakes was the only histologic pattern that was unique to mucinous areas. Its frequent association with cribriform Gleason grade 4 carcinoma suggests that it is a variant of grade 4 cancer, whose deviant appearance is a consequence of mucus hypersecretion. Collagenous stromal micronodules, found in 13 cases, are a previously undescribed and distinctive pattern thought to be a stromal reaction to contact with acidic extraluminal mucin. In grade 3 carcinoma, glands that secreted into the stroma rather than the gland lumen accounted for the stromal mucin, which appeared to lead to micronodule formation. In the grade 4 "colloid cancer" pattern, collagenous micronodules sometimes completely obliterated mucinous lakes, isolating residual cribriform glands in a "pseudo-grade 3" pattern. Lectin histochemical staining showed similar sialated and/or sulfated acidic mucin in all cases. Immunohistochemical staining showed downregulation of several differentiation antigens accompanying the alteration to mucinous differentiation.

Adenocarcinoma, Mucinous↗

Microcarcinoma in the prostate: its association with duct-acinar dysplasia.

In a series of 100 prostatectomy specimens obtained for adenocarcinoma, 107 additional incidental microscopic (less than 0.05 cm3) carcinomas were identified. Their morphologic features including location, histologic grade, and associated premalignant changes were documented. In 51 cases there was strong evidence of transition between microcarcinoma and the premalignant lesion, duct-acinar dysplasia. Invasive cancer was usually related to dysplasia through a characteristic intermediate morphologic stage of transitive glands. These glands were smaller than prostatic ducts; they appeared to arise by budding from dysplastic duct walls and showed the same distinctive lining epithelium. They were distinguished from invasive glands by their pseudo-stratified epithelial lining and by consistent association with a sparse, discontinuous basal cell layer. Cytoplasmic differentiation at the point of junction of invasive cancer with transitive or dysplastic glands was studied by immunohistochemical staining for the differentiation markers prostate-specific antigen and pepsinogen II, and staining for mucin. Markedly reduced cytoplasmic differentiation was common in dysplastic and transitive glands. Invasion often coincided with an abrupt increase in cytoplasmic differentiation with expression of ectopic differentiation products. This sequence of biologic changes should be tested in other carcinomas where the exact point of invasion can be identified.

Adenocarcinoma↗

Radical prostatectomy after definitive radiation therapy for prostate cancer.

Radical prostatectomy was performed in 14 patients following local failure of radiation therapy for adenocarcinoma of the prostate. Ten patients were treated with external beam and 4 with interstitial radiation. The interval from beginning radiation therapy to biopsy-proved residual or recurrent disease was twenty-four to one hundred fourteen months (mean 61 months). Ten patients had significant anterior and lateral fibrosis. Five patients had loss of tissue planes between the prostate and rectum, however, no rectal injuries occurred. Estimated blood loss was 300-8,000 cc (median 1,000 cc). Operative time was one hundred ten to three hundred seventy-five minutes (median 185 minutes). Significant late complications are impotence (100%) and incontinence (55%). Tumor volume was 1.1-27.2 cc (mean 11.1 cc). Seven patients had seminal vesicle involvement, 9 had level III capsule penetration, and 6 had positive surgical margins. Follow-up ranges from one to fifty-two months (median 18 months). Currently, 6 patients are clinically without disease and have serum prostate-specific antigen (PSA) of 0.0 ng/mL. Four patients have no clinical evidence of disease but do have detectable serum PSA, and 4 patients have evidence of metastatic bone disease on bone scan with elevated serum PSA levels. Radical prostatectomy following radiation therapy has no greater immediate morbidity or mortality compared with radical prostatectomy without prior irradiation and takes only slightly longer to perform. However, there is a marked increased risk of impotence and incontinence. More patients followed for a longer time are needed to assess the benefit of radical prostatectomy on survival of patients who fail radiation therapy.

Combined Modality Therapy↗

Efficacy of transrectal ultrasound for identification of clinically undetected prostate cancer.

A total of 51 patients underwent transrectal ultrasound of the prostate before radical cystoprostatectomy for transitional cell carcinoma of the bladder. Each had a normal prostate by digital rectal examination, no history of prostatic adenocarcinoma and no invasion of the prostate by transitional cell carcinoma. Real-time and step-sectioned ultrasound images were interpreted at the time of sonography and results were compared to pathological examination of the step-sectioned prostate specimen. When adenocarcinoma was identified in the specimen, cancer volume was determined. Positive ultrasound scans consisted of those exhibiting hypoechoic lesions. Hypoechogenicity due to transurethral resection defects, benign hyperplasia, vascular structures or shadowing from calcifications was not considered positive. Of 51 patients 27 (52.9%) exhibited no abnormality on ultrasound and were free of cancer in the prostate specimen, while 8 (15.7%) demonstrated a hypoechoic lesion that was proved to be prostate cancer. Seven patients (13.7%) with normal transrectal ultrasound scans had adenocarcinoma of the prostate, while 9 (17.6%) had lesions on ultrasound but no cancer. Based on these results, transrectal ultrasound has a sensitivity of 53.3% and a specificity of 75%. Further analysis reveals that transrectal ultrasound is more accurate in the detection of cancers of greater than 0.20 cc in volume than those of 0.20 cc or less. Transrectal ultrasound also is more accurate in the detection of peripheral zone than transition zone cancers.

Adult↗

Adjuvant radiation therapy in patients with detectable prostate specific antigen following radical prostatectomy.

Adjuvant radiation therapy following radical prostatectomy for adenocarcinoma of the prostate was given to 25 patients. Of these patients 8 had microscopic lymph node metastasis, 8 had seminal vesicle invasion without positive lymph nodes, 6 had positive surgical margins and 3 had only capsule penetration. Their only evidence of residual disease was detectable serum prostate specific antigen (PSA) by the Yang assay. A total of 15 patients (60%) had a subsequent decrease in PSA to less than 0.3 ng./ml. and an additional 5 (20%) had a decrease in PSA by more than 50%. Currently 8 patients have no detectable PSA after a median followup of 18 months (17 to 38 months) since initiating radiation therapy. Only 1 of 12 patients with detectable PSA immediately after radical prostatectomy has had a durable response to adjuvant radiation therapy. In contrast 7 of 13 patients with a delayed increase in PSA had a durable response. The ability of adjuvant radiation therapy to eliminate serum PSA in patients with a delayed increase in PSA after radical prostatectomy is encouraging. However, longer followup, including the use of nonradiated control subjects, is needed to assess the ability of adjuvant radiation therapy to control local disease and prolong patient survival.

Adenocarcinoma↗

Development of prostatic carcinoma. Morphometric and pathologic features of early stages.

The natural history of prostatic adenocarcinoma has been studied in a series of 261 radical prostatectomy specimens from Stanford. Total tumor histologic grade, cancer volume, zonal distribution of the tumor and correlation with its direction of spread, capsular penetration, seminal vesicle invasion and periprostatic extension were quantitated for each case. We identified specific morphologic and histologic features for cancers which arise in the anteromedial transition zone which contains BPH nodules, and for cancers which arise in the posterolateral peripheral zone. Stage A cancers are almost equivalent to transition cancers and stage B cancers to peripheral zone cancers. Prognosis as measured by lymph node metastasis was not different between these two groups of cancers but only related to their volume of poorly differentiated areas.

Adult↗

Serum markers in germ cell neoplasms.

Innovations in the treatment of testicular cancer, including surveillance of clinical stage I patients and curative chemotherapy for disseminated disease, have increased the need for sensitive ways to stage and monitor patients, both during and after therapy. Serum tumor markers, in combination with radiographic studies, have significantly improved our ability to evaluate and treat patients with seminomas and NSGCT. Elevated AFP and BHCG levels provide prognostic information at diagnosis, indicate persistent disease following orchiectomy or RPLND, and signal a recurrence after chemotherapy. Significantly delayed clearance of markers during chemotherapy often indicates persistent disease. Serum markers help define the duration of therapy, thus minimizing the substantial toxicities often associated with curative chemotherapy. Despite these advances, areas of concern remain. A small percentage of patients with NSGCT and the majority of patients with seminoma have undetectable levels of AFP and BHCG. The search for additional sensitive and specific serum markers in these cases has not been wholly successful. LDH, PLAP, and BFP occasionally serve as useful markers in seminoma but suffer lack of specificity. In addition, normal postoperative or postchemotherapy serum marker levels do not always ensure complete remission. This is difficult clinically when residual masses persist following therapy. Resection is always required to rule out persistent disease. The next decade may reveal additional useful serum tumor markers and potentially new imaging techniques incorporating antimarker antibodies to differentiate necrotic tissue from active disease.

Biomarkers, Tumor↗

Histologic differentiation, cancer volume, and pelvic lymph node metastasis in adenocarcinoma of the prostate.

The Gleason grading system for prostate cancer was applied quantitatively to analysis of entire tumors in 209 radical prostatectomy specimens from patients with clinical Stage A and Stage B carcinoma. Percentage of poorly differentiated tumor (Gleason histologic pattern 4 and/or 5) was related to quantitated cancer volume, cancer location within the prostate, and presence or absence of pelvic lymph node metastasis. A strong correlation was found between cancer volume, percentage of poorly differentiated cancer, and nodal metastasis. Twenty-two of 38 patients with more than 3.2 cc of Gleason histologic pattern 4-5 cancer had nodes with positive results, compared with one of 171 patients with less than 3.2 cc of pattern 4-5 cancer. Gleason histologic patterns 1 and 2 cancer was found mainly in a small subgroup of tumors whose site of origin was in the anatomic transition zone and whose volume was less than 1 cc. Gleason "cribriform" histologic pattern 3 cancer was thought to represent mainly intraductal carcinoma. Its increase in area with increasing cancer volume paralleled the increase in pattern 4 cancer and was counter to the decrease in other types of pattern 3 cancer.

Adenocarcinoma↗