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SUMMARY- Twelve patients with primary carcinoma arising in a vesical diverticulum are presented. Treatment included diverticulectorny with or without post-operative irradiation and transurethral resection. Recurrences were detected in 6 patients and the disease-free survival rate was 8%. [ABSTRACT FROM AUTHOR]

Purpose: To assess the antitumor activity of the benzothiopyranoindazole CI-958 ¿5-[(2-aminomethyl)amino]-2-[2-(diethylamino)ethyl]-2H- [l]benzothiopyrano[4,3,2-cd]-indazol-8-ol trihydrochloride¿ in hormone-resistant prostate carcinoma, using an intravenous dose of 700 mg/m(2) every 3 weeks., Patients and Methods: Patients eligible for this study had advanced prostate carcinoma that had failed hormonal treatment. Changes in an initially elevated prostate-specific antigen (PSA) level and regression of objectively measurable disease were used as response criteria., Results: All 33 patients enrolled were evaluated. Of 30 with elevated PSA levels, 6 had a >50% decline maintained for >30 days; response durations ranged from 105 to 623 days. Eleven patients had objectively measurable disease; two had partial responses (lasting 316 and 461 days) consisting of shrinkage of retroperitoneal nodes and of masses surrounding the rectum and bladder. The survival of all responding patients ranged from 366 days to 709 days and the median survival of all patients was 12 months (range 1-23 + months). Neutropenia was common, but thrombocytopenia was not. Nonhematologic side effects included nausea, vomiting, anorexia, asthenia, and chills, but were usually mild. The drug caused phlebitis when given into peripheral veins and central venous administration is recommended. No consistent reductions in cardiac function were documented by sequential assessment of left ventricular ejection fractions., Conclusions: CI-958 has modest but definite antitumor activity in hormone-resistant prostate carcinoma. Its toxicities include neutropenia, nausea, vomiting, anorexia, asthenia, chills and phlebitis.

Background: Between 20-30% of patients with advanced germ cell tumors relapse or fail to achieve a complete response to conventional cisplatin based chemotherapy. Ifosphamide has been used very effectively in combination with cisplatin and etoposide (VIP) or in combination with cisplatin and vinblastine (VeIP). Actinomycin D with chlorambucil and methotrexate was widely used in the 1960s with complete responses in 20% of patients and long term survival of 6-10%. There exists no information on the use of actinomycin as a salvage in cisplatin refractory patients., Methods and Results: One patient with metastatic germ cell tumor who failed chemotherapy with cisplatin and ifosphamide was successfully treated with an actinomycin D based regimen., Conclusions: Actinomycin D is an active agent in testicular cancer and maybe used in patients refractory to platinum.

Background: Methotrexate is readily absorbed from the intestinal tract. When given to patients with urinary diversion to the intestinal tract, methotrexate may be reabsorbed into the circulation, thus increasing its serum concentration and potentially increasing its toxicity., Methods: Forty-eight patients with transitional cell carcinoma of the urinary tract who had undergone cystectomy and either an ileal conduit or a continent diversion were evaluated for their tolerance of chemotherapy. Of the 42 evaluable patients, 23 had a continent diversion and 19 had an ileal conduit. None of the patients with the continent diversion had an indwelling Foley catheter during the course of chemotherapy., Results: There were no statistically significant differences in incidence of fever or neutropenia, mucositis, dose modification, or delay in chemotherapy between the two groups. When compared with a group of patients with native bladders who received the same chemotherapy, patients with continent diversions did not have increased incidence or severe toxicity from chemotherapy., Conclusions: Patients with continent diversions tolerated chemotherapy as well as patients with ileal conduits.

Purpose: The clinical impact of hematolymphoid malignancies discovered during radical prostatectomy has not been previously defined to our knowledge., Materials and Methods: From October 1988 to September 1995, 1,092 patients underwent radical retropubic prostatectomy., Results: Of 1,092 radical prostatectomy specimens, 13 (1.2%) were found to have hematologic malignancies involving the prostate and/or lymph nodes sampled during concomitant pelvic lymph node dissection. The malignancies detected included Hodgkin's disease (3) and hairy cell leukemia (1), which required further therapy. However, 9 of the 13 patients (62%) demonstrated either chronic lymphocytic leukemia (3) or low grade, small lymphocytic lymphoma (6), which requires symptomatic treatment only. The transrectal ultrasound guided prostate biopsies revealed suspicious lymphocytic infiltrate in addition to prostatic adenocarcinoma in 2 of the 13 patients (15%)., Conclusions: The majority of hematologic malignancies discovered at radical prostatectomy do not require further treatment and should not delay treatment of prostatic adenocarcinoma.

Purpose: To our knowledge the transrectal ultrasound appearance of prostatic granulomas occurring after intravesical bacillus Calmette-Guerin (BCG) therapy has not been thoroughly described., Materials and Methods: A total of 13 men with a history of transitional cell carcinoma of the bladder treated with intravesical BCG underwent transrectal ultrasound followed by prostate biopsy and/or cystoprostatectomy., Results: Of the 13 patients studied 9 (69.2%) had intensely hypoechoic lesions anteriorly in the transition zone of the prostate on ultrasound images. The lesions were histologically proved to be necrotizing granulomas., Conclusions: Prostatic granulomas secondary to BCG instillation appear as distinct, intensely hypoechoic anterior lesions within the transition zone of the prostate. Prostatic adenocarcinoma arising in the transition zone is usually not visible and would not be easily confused with granulomas. However, since transitional cell carcinoma involving the prostate can appear hypoechoic in the transition zone, transrectal or transurethral tissue sampling may be indicated.

We present a unique papillary thyroidlike carcinoma of the kidney. The patient had an incidentally discovered renal mass that, histologically and immunohistochemically, resembled papillary thyroid carcinoma. Workup revealed no primary site other than the kidney and no evidence of metastasis. This is the first reported case of a malignant papillary thyroidlike cancer of the kidney.

Erectile dysfunction was evaluated in 459 men with prostate cancer before and after radical prostatectomy. Potency was defined as the ability to achieve unassisted intercourse with vaginal penetration. Of the patients 51 were potent postoperatively, including 2 of 187 (1.1%) undergoing surgery without nerve sparing, and 27 of 203 (13.3%) undergoing unilateral and 22 of 69 (31.9%) undergoing bilateral nerve sparing prostatectomy. Less than half of the patients who were sexually active postoperatively were satisfied with the erections or achieved intercourse at least once a month. Postoperative potency was statistically related to the number of neurovascular bundles spared, frequency of intercourse preoperatively, absence of seminal vesicle or lymph node involvement with cancer, absence of postoperative incontinence or strictures, patient age and cancer volume.

Objective: To evaluate transrectal ultrasound as a means of diagnosis and of monitoring patients with rhabdomyosarcoma involving the prostate., Patients and Methods: Serial transrectal ultrasonography was utilized to evaluate prostatic rhabdomyosarcoma in three patients., Results: Unlike prostatic adenocarcinoma and transitional cell carcinoma involving the prostate, which are predominantly hypoechoic, the echogenicity of rhabdomyosarcoma is similar to that of the normal prostate. Transrectal ultrasound provided a simple means of monitoring prostate size and sampling tissue in these patients., Conclusion: Transrectal ultrasound imaging can be useful in both diagnosis and evaluation of treatment response as well as provide easy access for biopsies in patients with rhabdomyosarcoma involving the prostate.

A case of transitional cell carcinoma of the bladder metastasizing to the spermatic cord is reported. This represents the only clinically recognized site of tumor recurrence in a man treated with radical cystoprostatectomy followed by four cycles of adjuvant cis-platinum/methotrexate/vinblastine (CMV) chemotherapy for Stage D1 disease (local pelvic lymph node involvement). The existing literature concerning metastatic tumors of the spermatic cord is reviewed.

The natural history of prostate cancer has long been regarded as unpredictable. The discrepancy between histologically identifiable (40%) and clinically diagnosed carcinomas (8%) led to the term of "latent" prostate cancer and to considerable diagnostic and therapeutic dilemmas. Based on our previous studies showing that biological aggressivity of prostate cancer is a direct function of tumor volume and that tumor volume and serum PSA are proportional, we evaluated two basically different groups of patients. The first group consisted of 43 patients with untreated carcinomas of the prostate followed with serial PSA determinations. The exponential (log-linear) rise in PSA led us to the conclusion of an exponential tumor growth rate. The median doubling time of clinically organ-confined tumors was 4 years and became shorter with higher clinical stages and poorly differentiated histological grades. The second group consisted of 139 patients who underwent cystoprostatectomy for bladder cancer and had no evidence for simultaneously identifiable prostate cancer. In 55 patients (40%), unsuspected prostate cancer was found in the specimen; the volume distribution of these carcinomas was exponential. These 139 men included 11 (7.9%) who had a prostate cancer with a volume greater than 0.5 cm3, corresponding to the 8% risk for a man being diagnosed within his lifetime with a clinically significant carcinoma of the prostate. We conclude that the other 44 carcinomas, which were less than 0.5 cm3 in volume, will never reach clinical significance because of their small size and their long doubling time; in this sense they can be considered latent.(ABSTRACT TRUNCATED AT 250 WORDS)

Transitional cell carcinoma of the upper urinary tract is rare. Tumors arising in the renal pelvis and calyces should be treated with nephroureterectomy, irrespective of stage and grade. Low-grade, low-stage ureteral tumors may be treated with conservative resection in order to preserve renal function. High-grade, more advanced ureteral tumors should be treated with nephroureterectomy because of the high incidence of recurrence associated with local resection. The role of lymphadenectomy for upper tract transitional cell carcinoma has never been evaluated; however, it is recommended for better staging of the disease and for recommendations regarding adjuvant therapy. Adjuvant radiation therapy to sterilize microscopic residual disease and prevent local recurrence is logical. The role of adjuvant chemotherapy is under investigation.

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.

Chemotherapy with cisplatin, methotrexate and vinblastine (CMV) is active in advanced transitional cell carcinoma of the urothelium. Aggressive surgical resection of residual disease following responses produced by CMV was incorporated into a combined modality approach. Between 1982 and 1990, 64 patients were entered into the study. Of 55 patients evaluable for response 11 (20%) had a pathological complete response, 14 (25%) achieved a complete response following resection of residual disease and 5 (9%) whose disease was not surgically restaged had a clinical complete response. The overall complete response rate was 55%. Patients with liver, lung or bone involvement had significantly decreased survival compared to patients without visceral disease (p = 0.002). With a median followup exceeding 50 months, 14 patients (22% of all patients entered into the study) were free of disease at 23 to 98+ months. There were no deaths related to treatment. CMV produced high rates of response in patients with advanced disease, including those with distant metastases. Surgical resection of residual disease following responses produced by chemotherapy proved to be feasible, without treatment related mortality, and may have prolonged survival in selected cases.

Detection of microscopic seminal vesicle invasion with prostate cancer by transrectal ultrasound-guided seminal vesicle biopsies provides a method of evaluation that is much less subjective than digital rectal examination or imaging techniques. The accuracy of seminal vesicle biopsy is analyzed in 73 patients undergoing transrectal ultrasound-guided biopsy of 145 seminal vesicles followed by radical prostatectomy. Of 133 benign seminal vesicle biopsies 11 (8.3%) were found in the surgical specimen to have cancer involving an average of 6% of the seminal vesicle area. Of 8 seminal vesicle biopsies showing cancer adjacent to seminal vesicle epithelium 100% demonstrated seminal vesicle invasion in the surgical specimen extending for an average of 19% of the seminal vesicle area. Three biopsies exhibited cancer but no seminal vesicle epithelium; only 1 (33%) of these had seminal vesicle invasion for 5% of the seminal vesicle area. One biopsy revealed normal prostate tissue. Careful placement of bilateral biopsy sites cephalad to the prostate base (not traversing any portion of the prostate gland) is recommended. Caution should be exercised when basing treatment decisions on seminal vesicle biopsies that do not reveal seminal vesicle epithelium histologically.

We evaluated the usefulness of an ultrasensitive immunoassay for prostate specific antigen (PSA), modified from the standard Yang Pros-Check PSA test and with a biological detection limit for PSA in serum of 0.07 ng./ml., to detect residual prostate cancer at an earlier date. We studied retrospectively serial frozen serum samples from 22 prostate cancer patients after radical prostatectomy who later had residual cancer with detectable PSA levels of 0.3 ng./ml. or more by the standard PSA test. As controls we studied 33 cystoprostatectomy patients (for bladder cancer) without histological evidence of prostate cancer and 23 patients after radical prostatectomy who had the highest probability of cure of the cancer. All control patients without cancer had PSA values (282 of 283 samples, 99.6%) of less than 0.1 ng./ml. This value was called the residual cancer detection limit. In the 22 patients with recurrent cancer the ultrasensitive assay detected cancer recurrence (PSA 0.1 ng./ml. or more) much earlier (median 202 and mean 310 days) than the standard assay (PSA 0.3 ng./ml. or more). On screening 187 current post-radical prostatectomy patients without evidence of cancer by the standard assay the ultrasensitive assay detected 21 (11.2%) with evidence of residual cancer, that is PSA level of 0.1 ng./ml. or more. We conclude that an ultrasensitive assay for PSA can detect residual cancer after radical prostatectomy much earlier than current immunoassays for PSA. Earlier detection of residual cancer may improve long-term survival by allowing for earlier institution of adjuvant therapy.

Denonvilliers' fascia consists of a single fibromuscular structure covering the posterior aspect of the prostate and surrounding the seminal vesicles. This structure has multiple layers that are fused together, and to the stroma of the prostate and seminal vesicles. A separate posterior layer of Denonvilliers' fascia was not seen during radical prostatectomy. The cleavable interprostatorectal plane extends posteriorly throughout the thickness of Denonvilliers' fascia and anteriorly to the muscular wall of the rectum. Medially this fascia is fused with the prostatic capsule into a single sheath and contains thick smooth muscle bundles in continuity with the prostatic stroma. In a series of 243 radical prostatectomy specimens for prostate cancer, we studied the morphological relationship of Denonvilliers' fascia with the prostatic capsule and stroma, and traced the progression of prostatic cancer in relation to the anatomical landmarks. In 19% of the cases tumor was found progressing within Denonvilliers' fascia, in the medial posterior area of the prostate, unrelated to perineural space invasion. For specimens with an intracapsular cancer volume of less than 12 cc, which may be cured by radical prostatectomy alone, the frequency of invasion of Denonvilliers' fascia was 13%. In these cases cephalad progression of cancer was seen almost exclusively in Denonvilliers' fascia overlying the central zone at the prostate base and surrounding the seminal vesicles. Invasion of Denonvilliers' fascia can lead to positive surgical margins if complete excision of this fascia is not performed during radical prostatectomy. Even among large tumors in our series there were no cases of tumor invasion completely through the full thickness of Denonvilliers' fascia at the posterior medial area and, therefore, rectal wall invasion was never suspected at this level.

Background: Using the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute and American total mortality rates, the authors calculated the probability at birth of having a diagnosis of prostate cancer within a man's life to be 8.8% and then subtracted the incidence of microscopic Stage A cancers too small to ever be clinically significant. This gave a final probability of 8%., Methods: Prostates were examined after 139 consecutive unselected cystoprostatectomies from patients with bladder cancers in whom it was unknown whether they had prostate cancer. Prostate cancer was found in 55 patients (40%); the volume of the largest cancer in each specimen was determined using histologic morphometry. The authors identified the 8% of these 139 cytoprostatectomy specimens with the largest volume of prostate cancer., Results: The largest 11 of the 55 cancers represented 7.9% of the total 139 samples. These cancers ranged in volume from 0.5-6.1 ml, representing only 20% of all patients with prostate cancer., Conclusions: If the strong evidence is accepted that cancer progression is proportional to cancer volume, it was concluded that prostate cancers larger than 0.5 ml appear to correspond to the 8% of men who will be diagnosed with a clinically significant carcinoma, as derived previously. Conversely, those 80% of prostate cancers smaller than 0.5 ml probably are not likely to reach a clinically significant size in view of the long doubling time of this cancer.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.