Biomedical subjects
Publications and source records attributed to F S Freiha.
Two cases of bladder leiomyoma are reported. Both are women who presented with a palpable mass on pelvic examination, one asymptomatic and the second with significant bladder outlet obstruction. Results of ultrasound examinations are presented. Complete local resection was curative in both patients.
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A retrospective study of 30 adults who underwent supravesical diversion for a variety of benign and malignant conditions was done with special attention to the fate of the residual bladder. Diversion was performed for diverse conditions, including radiation cystitis, cyclophosphamide cystitis, interstitial cystitis, incontinence and trauma. All groups experienced significant morbidity from the remaining in situ bladder. Over-all, 80% of the patients experienced at least 1 complication, chief among which were pyocystis (67%), hemorrhage (23%), severe pain (13%), and unremitting feelings of incomplete emptying and spasm (17%). Complications of sufficient severity to require rehospitalization occurred in 43% of the patients. Several patients required multiple rehospitalizations. Reoperation requiring general or regional anesthesia was necessary in 9 patients (30%) and included 4 cystectomies. Serious consideration should be given to performing primary cystectomy at the time of supravesical diversion in any patient in whom subsequent undiversion is not anticipated.
Acute, fulminant bladder hemorrhage usually is seen at tertiary care centers in which cancer patients are treated with oxazaphosphorine alkylating agents, particularly cyclophosphamide and isophosphamide. These agents also are used to treat benign conditions, such as lupus erythematosis and Wegener's granulomatosis. Radiation effects from treatment of prostatic or cervical carcinoma can appear for the first time as late as 15 to 20 years after initial treatment. Other iatrogenic causes of bleeding include treatment with penicillins and, rarely, danazol. Occasionally, bladder hemorrhage may be the presenting sign of metabolic disease, such as secondary amyloidosis in rheumatic arthritis. Cases of mild to moderate hemorrhagic cystitis arising in the otherwise healthy patients should lead one to pursue the possibility of environmental toxins, accidental poisoning, recreational drug use or viruses. In all cases the diagnosis should be reserved until more common causes of hematuria, such as bacterial or fungal infection, stones, cysts or tumors, have been ruled out. Prevention of chemotherapeutically induced cystitis ideally will follow careful attention to adequate hydration and the prophylactic use of antitoxins, such as mesna. Treatment, as outlined previously, consists of a series of measures beginning with the most conservative. Intervention thereby is tailored to the gravity of the clinical situation.
Positive margins were analyzed in 189 clinical stage B radical retropubic prostatectomies. Margins were identified by serially blocking the entire specimens in planes selected for optimum demonstration of capsule surface. Positive margins were divided into 2 categories: 1) those associated with capsular penetration of cancer and 2) those caused by inadvertent surgical incisions through the capsule into intracapsular cancer. Data were analyzed separately at each of 6 anatomical sites. Frequency of positive margins was related to the volume of cancer. Cancer of greater than 12 cc constituted a distinctive category in which seminal vesicle invasion, lymph node metastases and multiple positive margins were found in the majority of cases, signifying minimal possibility of cure. However, 31 positive margins occurred among 136 patients (23%) who were potentially curable by the criteria of normal seminal vesicles and absence of pelvic lymph node metastases; 17, of these 31 surgically positive margins (55%) occurred at the apex. Positive capsular penetration margins at the apex were volume-related, while negative margins were not. Site specific recommendations for avoiding positive and negative capsular penetration margins are suggested. The prostate apex, rectal and lateral surfaces, bladder neck and superior pedicles accounted for 48, 24, 16 and 10% of all positive margins, respectively. Dissection of the apical prostate and Denonvilliers' fascia require modifications of current surgical techniques if positive margins are to be avoided. Serum levels of prostate specific antigen may require as long as 5 years to become detectable when only 1 positive margin is the only evidence of nonorgan-confined disease.
Seminal vesicle invasion and the percentage involvement by cancer of each seminal vesicle were related to cancer volume, quantitative histological grade and presence or absence of lymph node metastases in 243 radical prostatectomy specimens. There were 47 prostates with seminal vesicle invasion. Frequency and extent of seminal vesicle invasion were strongly correlated with cancer volume, with minimal invasion noted in only 6% of the cases less than 4 cc. The relationship of seminal vesicle invasion to lymph node metastasis was statistically significant but cancer volume and histological grade were much stronger predictors of lymph node metastasis. The route of invasion from the prostate in 46 cases involved direct tumor spread into the midbase region near the ejaculatory ducts. Seminal vesicle invasion often may not be identified if the tissue nearest the ejaculatory ducts at the prostate base is not sampled.
We established the location and extent of complete capsule penetration by prostate cancer in 176 radical prostatectomy specimens and related these findings to cancer volume, location of positive surgical margins, and presence of nodal metastases or seminal vesicle (SV) invasion. Extent of capsule penetration, cancer volume, and positive nodes/SV were strongly intercorrelated. It could not be shown that capsule penetration was related to prognosis independently of its correlation with cancer volume. Twelve cubic centimeters was a critical cancer volume; above that, combinations of extensive capsule penetration, positive surgical margins, and positive nodes/SV were almost universal. In cancers under 12 cc, positive surgical margins were only moderately correlated with cancer volume; they often represented surgical resection into the capsule rather than a complication of capsule penetration by tumor and were most common at the apex, where dissection is most difficult. In non-transition zone cancers (148 cases), capsule penetration was most common posterolaterally, where nerves penetrate the capsule. In transition zone cancers (28 cases), capsule penetration was much less common and was located more anteriorly. Apical positive margins were also relatively common in transition zone cancers, but seminal vesicle invasion was never seen.
Prostatic involvement with transitional cell carcinoma of the bladder is common. Surveillance for prostatic invasion consists primarily of cystoscopic examination of the urethra. Unfortunately, transitional cell carcinoma may involve other regions of the prostate that are inaccessible by cystoscopy. A total of 58 men with transitional cell carcinoma of the bladder underwent transrectal ultrasound before cystoprostatectomy or, in some cases, ultrasound-guided prostate biopsies and subsequent cystoprostatectomy. Prostatic involvement was found in 20 patients (34.5%). Of those patients 10 (50%) demonstrated prostatic urethra invasion, 7 (35%) stromal invasion, 4 (20%) ejaculatory duct and seminal vesicle invasion, and 3 (15%) involvement of the periprostatic tissues. Invasion of the prostatic urethra was not detected by transrectal ultrasound but 5 of the 7 stromal lesions exhibited hypoechogenicity. All cancer-laden ejaculatory ducts were hypoechoic on ultrasound examination. All cases of periprostatic involvement were also detectable by corresponding areas of hypoechogenicity. Transrectal ultrasound may enhance the surveillance of men with transitional cell carcinoma.
Transrectal, ultrasound guided needle biopsies were performed in 27 men greater than 18 months (mean 5.2 years) after radiation therapy for prostate cancer. Of the patients 18 (67 per cent) originally had localized (stage A or B), 6 had stage C and 3 had stage D1 prostate cancer. In addition to biopsies directed at any hypoechoic regions of the prostate, multiple systematic biopsies were performed from the apex to the base bilaterally and the seminal vesicles also were biopsied regardless of appearance. Of 27 patients 25 (93 per cent) had post-irradiation biopsies positive for cancer, including 5 of 5 with prostate induration and 20 of 22 (91 per cent) with normal post-irradiation digital rectal examinations. Ultrasound findings per se were poorly correlated with pathological findings in the irradiated prostate. Directed biopsies of hypoechoic areas were positive for cancer in 67 per cent of the cases and isoechoic areas were positive for cancer in 65 per cent. Seminal vesicle biopsies were positive in 7 patients (26 per cent), including 4 with normal post-irradiation rectal examinations and 4 with normal ultrasound appearance. Of 12 patients 10 (83 per cent) with serum prostate specific antigen levels less than 10 ng. per ml. had positive biopsies, as did all 15 with levels greater than 10 ng. per ml.
In 176 radical prostatectomy specimens areas of capsule penetration by cancer and positive surgical margins were quantified and located over the prostate surface. The presence of cancer within the perineural space was sought in these areas and compared to the normal distribution of prostatic nerve branches. Capsule penetration was found in 78 of 156 stage B carcinomas, and in 39 of these 78 (50 per cent) it occurred entirely by cancer extension through the capsule within perineural spaces. In the remaining 39 prostates capsule penetration by perineural space invasion predominated but direct spread also was found. Most often, perineural space invasion followed the oblique vertical course of nerve branches that extended superiorly to the superior pedicle near the prostate base. In such cases capsule penetration areas were localized near the superior margin of the cancer, and in 11 per cent positive superior pedicle margins resulted from continued perineural space invasion outside the capsule. In cancers near the prostate apex capsule penetration by perineural space invasion produced positive margins in 89 per cent of 18 cases because of the short inferior pedicle. The role of perineural space invasion by cancer was less prominent in 4 of 20 stage A cancers that showed capsule penetration.
Injectable materials have been used to augment the urethral sphincter and improve urinary continence with some success. However, none of these materials has received widespread use because they are difficult to inject and have been reported to migrate. We investigated the efficacy of transurethral implantation of glutaraldehyde cross-linked collagen, a highly purified bovine collagen. A total of 17 patients (16 men and 1 woman) with urinary incontinence resulting from a previous operation was selected for glutaraldehyde cross-linked collagen injection into the region of the urethral sphincter. Before and after implantation patients underwent urodynamic evaluation. Glutaraldehyde cross-linked collagen was injected into the area of the bladder neck or urinary sphincter under direct endoscopic vision. If no improvement occurred reinjection to increase the implant volume was performed at least 3 months after a previous injection. Of the 17 patients 9 were cured or improved. No complications have been reported. This investigation shows that glutaraldehyde cross-linked collagen can be injected into the urinary tract to correct urinary incontinence without observable or measurable morbidity.
Cystoprostatectomy specimens were evaluated in 66 male patients operated on for a pathological condition of the bladder with no evidence of prostatic malignancy on preoperative clinical assessment. There were 38 prostate cancers identified in 25 of 66 patients (38 per cent). Multiple foci of adenocarcinoma were noted in 10 of 25 patients (40 per cent). The mean tumor volume was 0.11 cc, with half of the cancers being less than or equal to 0.01 cc in volume. All 38 cancers were completely localized to the prostate and exact anatomical sites of origin for each of the cancers within the prostate were mapped. Whereas anatomical distribution of the cancers in the anteroposterior dimension was roughly uniform, a distinct predominance of apical prostatic cancers was observed. Possible anatomical explanations and implications of these findings in terms of the apical surgical margins at radical prostatectomy and cystoprostatectomy, and the new technologies currently available for diagnosis of prostate cancer are discussed.
The cellular distribution of tissue plasminogen activator in the prostate central zone, prostate peripheral zone, and seminal vesicle was studied by using immunohistochemistry. Samples of these three regions were taken from 20 radical prostatectomy specimens. Sixteen of 18 central zone samples showed positive staining of 20-90% of the epithelial cells. All 15 peripheral zone samples were negative, and only three of 14 seminal vesicles showed positive staining, which was present in less than 5% of cells. The distribution of tissue plasminogen activator within the prostate was the same as that previously reported for pepsinogen II. This suggests that the central zone of the prostate may be the selective site of origin for proteolytic enzymes in seminal fluid.
We present our experience with 4 patients with transitional cell carcinoma of the bladder and brain metastases. In all 4 cases a solitary intracranial metastasis occurred. In 3 patients this represented the first site of recurrent disease following systemic chemotherapy. Aggressive therapy of the brain metastases was instituted in 3 patients, including external beam radiation and in 2 cases surgical resection. Although all patients died only 3 died as a result of metastatic transitional cell carcinoma, including 2 who died as a direct result of intracranial disease. A review of the literature suggests an increasing incidence of brain metastases from transitional cell carcinoma of the bladder with the advent of more aggressive therapy for bladder cancer, which includes radical surgery for high stage disease and combination chemotherapy. Aggressive intervention for solitary brain metastases from transitional cell carcinoma can relieve neurological dysfunction and may prolong survival.
Morphological features in radical prostatectomy specimens from 11 stage A and 73 stage B prostatic carcinomas were compared by mapping of tumor locations, and determinations of cancer volumes and histological patterns. Small stage A cancers were located anteromedially, while small stage B carcinomas were concentrated against the posterior capsule at the rectal surface. Small stage A carcinomas commonly invaded the anterior fibromuscular stroma and benign prostatic hyperplasia nodules, features that were uncommon even in large stage B tumors. Stage A cancers often appeared to arise within benign prostatic hyperplasia nodules and had a distinctive histological appearance. Even when large, stage A carcinomas tended not to spread close to the rectal surface of the gland. Stages A and B cancers spanned a roughly comparable volume range, and both showed progressive dedifferentiation with increasing volume. It is proposed that stages A and B cancers are biologically similar malignancies, distinguished only by their site of origin. Prognosis for patients with stage A carcinoma probably is closely related to tumor volume and dedifferentiation, features that are not reliably estimated in tissue samples removed at operation for benign prostatic hyperplasia.
Morphometric reconstructions of 68 consecutive radical prostatectomies were analyzed for cancer volume, extent of complete capsular penetration, microscopic seminal vesicle and lymph node invasion, and histological differentiation, all of which were strongly interrelated. At less than 3.0 cc cancer volume, only 6 of 34 prostates (18 per cent) showed capsular penetration compared to 27 of 34 (79 per cent) with tumors of greater than 3.0 cc. Seminal vesicle invasion occurred once in 34 tumors of less than 3.0 cc and 15 times in those greater than 3.0 cc. All 6 patients with metastases to lymph nodes, 2 with early postoperative development of bone metastases and 4 of 5 with reappearance of detectable prostate specific antigen postoperatively had cancer volumes of greater than 4.0 cc. Correlation of digital rectal examination with cancer volume showed that of 39 palpable nodules in prostates with a cancer volume of less than 4.0 cc 30 (77 per cent) occupied 50 per cent or less of the length of 1 lobe (clinical stage B1 in our classification). Of 22 palpable lesions in tumors of greater than 4.0 cc 21 (95 per cent) exceeded 50 per cent of 1 lobe in the longitudinal extension (stage B2) or they represented bilaterally palpable disease (stage B3). Capsular penetration into the periprostatic fat occurred most commonly in the dorsolateral area of the neurovascular bundle, including 10 of 12 tumors less than 4.0 cc in volume (stage B1) and 19 of 21 with greater than 4.0 cc in tumor volume (stages B2 and B3). All 10 of the stage B1 cancers were free of contralateral lobe capsular penetration while 1 of the 13 stage B2 nodules had minimal contralateral capsule penetration in the area of the neurovascular bundle. We believe that the modified nerve-sparing radical prostatectomy should be limited to the contralateral side in stage B disease.
Epithelial cell differentiation was evaluated in 15 samples of duct-acinar dysplasia, a putative premalignant lesion of the prostate, through immunohistochemical staining for five differentiation markers. Prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), Leu-7, pepsinogen II (PG II), and tissue plasminogen activator (t-PA) are all constituents of seminal fluid that are produced by prostatic epithelium. Dysplasia foci were classified into three grades of severity and their locations mapped by camera lucida drawings of each slide. The degree of abnormal staining with each antibody was recorded on the map, and its correlation with dysplasia grade was evaluated. PSA, PAP, and Leu-7 staining were reduced in dysplasia and often absent in severe dysplasia, indicating that reduced differentiation is an early change in prostatic carcinogenesis. PG II and t-PA stains were sometimes positive in a region where they are usually absent, suggesting that deregulation of differentiation markers may accompany reduction in differentiation in these preneoplastic lesions.
For 104 prostate glands obtained at radical prostatectomy for adenocarcinoma, we mapped the tumor outline and determined the tumor volume, grade, and location relative to the transition zone boundary and location of the central zone. Among the 88 cancers whose probable zone of origin could be identified, 68% arose in the peripheral zone, 24% arose in the transition zone, and 8% arose in the central zone. Transition zone carcinomas had usually been diagnosed by transurethral resection (TUR) and often appeared to arise within BPH nodules; only two of 67 non-transition zone carcinomas had been diagnosed at TUR. Two-thirds of 21 transition zone cancers showed a distinctive histologic appearance; they were made up of columnar clear cells lining glands of widely variable size and contour. The transition zone boundary appeared to act as a barrier to the spread of non-transition zone carcinomas. We conclude that carcinoma typically arises in the region of the prostate that is susceptible to benign prostatic hyperplasia and that the great majority of Stage A (TUR) cancers are transition zone cancers. Non-transition zone cancers detectable at TUR are predominantly large tumors that are poorly differentiated and lack the clear cell histologic pattern.