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Biomedical subjects

E E Fraley

Publications and source records attributed to E E Fraley.

At least 19 recordsLinked to original sources

Extragonadal abdominal germ cell cancers.

The charts of eleven patients with abdominal germ cell tumors were reviewed; one had a seminoma. They all had normal testes by physical examination. Therapy consisted of cisplatin-based chemotherapy and, in some cases, surgical debulking. A complete clinical response occurred in seven patients (63%). Two patients relapsed after achieving pathology complete responses and died of progressive disease despite second-line chemotherapy. All patients that failed to achieve a complete clinical response died of progressive disease. Five patients (45%) are long-term disease-free survivors, having no recurrence 4-10 years from the time of the diagnosis (median 6 years). The outcome for this group of patients did not differ significantly from that for patients with mediastinal germ cell tumors in this institution. They do not fare as well as patients with testicular cancer.

Adolescent

Total bladder replacement using detubularized sigmoid colon: technique and results.

We performed total bladder replacement with a detubularized segment of sigmoid colon in patients after cystoprostatectomy. The surgical technique and long-term results in 27 patients are reported. This neobladder configuration compared favorably with other neobladder types regarding ease of construction. The surgical complications were acceptable. Initial reservoir function was good but improved further with time. After 1 year the capacity averaged 600 cc, pressures during filling and at capacity were low (average 12 and 16 cm. water) and emptying was satisfactory (residual urine 4 to 80 cc). All patients were continent during the day and 67% were continent at night without excessive voiding habits. Nighttime incontinence was further resolved in 2 patients by using the AMS 800 artificial sphincter around the bulbous urethra. The detubularized sigmoid is an excellent neobladder configuration after cystoprostatectomy.

Carcinoma, Transitional Cell

Epidermoid cyst (monodermal teratoma) of the testis.

We report 14 patients with epidermoid cyst of the testis (monodermal teratoma). In 7 patients (5 treated within the last 5 years) the mass was excised and adjacent testicular tissue was biopsied. Seven patients underwent radical inguinal orchiectomy. Carcinoma in situ was not detected in any testicular tissue examined. There was no evidence of tumour recurrence in any patient after a mean follow-up of 10 years. Ultrasonographic appearance was not specific for a diagnosis of epidermoid cyst and exploratory surgery was required in all cases. Excision of the tumour and biopsy of adjacent testicular tissue to determine the presence or absence of carcinoma in situ is adequate treatment for this rare testicular neoplasm.

Adult

Intratubular germ cell neoplasia in testicular teratomas and epidermoid cysts. Correlation with prognosis and possible biologic significance.

The clinicopathologic features of 4 testicular teratomas in infants, 13 testicular epidermoid cysts in adults, and 8 pure teratomas in adults were compared. Intratubular germ cell neoplasia (ITGCN, carcinoma in situ) was observed in 88% of the teratomas in adults; 63% of the patients in this group had metastases and 37% died. No ITGCN was observed in infant testes with teratomas or adult testes with epidermoid cysts; all of the neoplasms in the latter two groups behaved as benign tumors. ITGCN is associated with malignant potential (P = 0.0004; Fisher's exact test). These tumors comprise a spectrum of clinicopathologic entities that probably reflect differences in pathogenesis.

Adult

The role of ilioinguinal lymphadenectomy and significance of histological differentiation in treatment of carcinoma of the penis.

We reviewed retrospectively the medical records of 58 patients treated for squamous cell carcinoma of the penis who were followed for more than 3 years or until they died. Tissue sections from all patients were reviewed. Of 15 patients with stage I disease 11 underwent partial penectomy, and 4 underwent partial penectomy and immediate ilioinguinal lymphadenectomy; none died of cancer. Nine patients with stage II and 9 with stage III disease underwent partial or total penectomy and immediate ilioinguinal lymphadenectomy, and 5-year survival was 100 and 75%, respectively. Of 20 patients with clinical stage II disease who did not undergo immediate ilioinguinal lymphadenectomy 18 had metastasis to the groin. Of these 18 patients 12 underwent delayed ilioinguinal lymphadenectomy but only 1 survived more than 5 years. We evaluated the possible significance of the degree of histological differentiation of the primary tumor to the course of the disease. Of the 23 cases of carcinoma in situ or well differentiated disease only 1 became metastatic, while of the 35 cases of moderately to poorly differentiated disease 31 metastasized to the groin. Vascular invasion of cancer cells in the primary tumor was another indicator for poor prognosis.

Aged

The value of serum prostate specific antigen determinations before and after radical prostatectomy.

We evaluated serum prostate specific antigen before and after radical prostatectomy. In 100 consecutive patients who underwent radical prostatectomy, preoperative prostate specific antigen levels tended to increase with the increasing severity of pathological stage. However, even at levels of greater than 10 ng. per ml. the positive and negative predictive values (78 and 61 per cent, respectively) of prostate specific antigen to predict extracapsular disease were not sufficient to make this test useful alone for staging. In theory, after radical prostatectomy prostate specific antigen should be zero if no remaining prostatic tissue is present. Tests of precision and analytical sensitivity in our laboratory using a commercial prostate specific antigen assay revealed that a value of 0.4 ng. per ml. or more is different from zero at a greater than 95 per cent confidence level. With this guideline we evaluated the meaning of prostate specific antigen levels 3 to 6 months after radical prostatectomy in 59 men. Among men whose prostate specific antigen level was less than 0.4 ng. per ml. only 9 per cent demonstrated recurrence as evidenced by the development of positive bone scan or progressively elevated prostate specific antigen levels within 6 to 50 months. Alternatively, in men whose 3 to 6-month prostate specific antigen level was 0.4 ng per ml. or more there was evidence of recurrence in 100 per cent within 6 to 49 months (p less than 0.0001). Progressively elevated (more than 0.4 ng. per ml.) prostate specific antigen levels preceded recurrence from 12 to 43 months in all 6 patients who had positive bone scans, while increasing prostate specific antigen levels since radical prostatectomy have continued from 9 to 65 months in the 11 patients who have no radiological evidence of recurrent disease to date. Prostatic acid phosphatase serum values after radical prostatectomy were not useful to predict persistent disease. Prostate specific antigen values 3 to 6 months after radical prostatectomy are a sensitive indicator of persistent disease after radical prostatectomy and often precede other evidence of this occurrence by many years. This fact may alter concepts about surgical results, and possibly shorten and sharpen clinical studies involving adjuvant therapy after radical prostatectomy.

Acid Phosphatase

Sarcomas of the retroperitoneum and genitourinary tract.

A total of 62 patients with retroperitoneal or genitourinary sarcoma was treated at our institutions during the last 46 years. Of the patients 51 were followed for at least 5 years or until they died (median followup 11 years); 5 patients were lost to followup. The most common site was the retroperitoneum. Liposarcoma, leiomyosarcoma and malignant fibrous histiocytoma were the most common tumors (74 per cent). Tumors were completely resected in 42 patients (68 per cent) and incompletely resected in 11, while a biopsy only was performed in 9. Some patients also received adjuvant radiation therapy and/or chemotherapy. There were no long-term survivors among patients with unresectable tumors. Over-all 3 and 5-year survival rates were 68 and 39 per cent, respectively. The histological type of the tumor appeared to have prognostic significance. The highest 5-year survivals were for liposarcoma (70 per cent), malignant fibrous histiocytoma (33 per cent) and leiomyosarcoma (13 per cent). The mean survival for patients after adjuvant radiation therapy or chemotherapy was similar to that after a radical operation alone. The primary cause of treatment failure was local recurrence (45 per cent of the patients), which was detected within 3 years of complete resection in most cases (82 per cent). Complete extirpation that provided adequate margins free of tumor was the most effective initial treatment and provided the best chance for cure.

Combined Modality Therapy

Endoscopic treatment of posterior urethral obliteration: long-term followup and comparison with transpubic urethroplasty.

We compare our results with the endoscopic management of posterior urethral obliteration in 8 patients to our previous experience with transpubic urethroplasty in 6 patients. Although most patients who underwent an endoscopic procedure required 2 or 3 followup internal urethrotomies within the first 2 to 10 months after treatment, 6 have remained free of stricture for more than 2 years after this initial period of aggressive endoscopic management. This finding suggests that total obliteration of the posterior urethra can be managed effectively by endoscopic techniques. Comparison of endoscopic treatment with transpubic urethroplasty revealed a decrease in operative time, blood loss and hospital stay with endoscopic management. We recommend that transpubic urethroplasty be reserved for patients in whom urethral continuity cannot be re-established with relatively safe and simple endourological techniques.

Adult

Progressive metastatic renal cell carcinoma controlled by continuous 5-fluoro-2-deoxyuridine infusion.

We treated 19 patients with progressive metastatic renal cell carcinoma with continuous infusion of 5-fluoro-2-deoxyuridine, 52 per cent of whom had previously received and failed chemotherapy. Implantable pumps were used for automatic drug delivery. 5-Fluoro-2-deoxyuridine was infused continuously for 14 days at monthly intervals. The starting dose was 0.15 mg. per kg. per day (intravenous) or 0.25 mg. per kg. per day (intra-arterial). Intravenous doses were increased or decreased in increments of 0.025 mg. per kg. per day as permitted by toxicity. Abdominal pain, diarrhea and mucositis limited the intravenous infusion, while malaise, anorexia and hepatic function abnormalities limited intra-arterial infusion. Of 18 evaluable patients we observed 1 complete, 4 partial (objective response rate 28 per cent) and 2 minor responses. The duration of response ranged from 2 to greater than 18 months. During a median follow up of 7.5 months (range 2 to 21 months) only 4 of the 18 patients had objective tumor progression. Over-all survival for the 19 patients was 94 per cent. Continuous infusion of 5-fluoro-2-deoxyuridine may be effective for the treatment of progressive renal cell carcinoma.

Adult

Radiation therapy as adjuvant treatment after radical prostatectomy.

Between 1977 and 1984, adjuvant radiation therapy was administered after radical prostatectomy to 71 patients at high risk for recurrence of carcinoma of the prostate. In 35 patients, tumor remained at the surgical margin (stage C2 disease) and/or the disease had invaded the seminal vesicles (stage C3). Thirty-six patients had microscopic metastases in the pelvic lymph nodes (stage D1a). Radiation therapy was administered only after full recovery from surgery, which included full recovery of continence. The average period between surgery and initiation of radiation therapy was 3 months. Serious or long-term complications attributable to irradiation occurred in 7% of the patients. Tumor recurred locally in only 2 patients. Five-year actuarial survival, disease-related survival, and disease-free survival for patients with stage C2 and C3 disease were 86%, 96%, and 80%, respectively. These survival values for patients with stage D1a disease were 74%, 90%, and 69%, respectively. Our results suggest a greater therapeutic benefit from radical prostatectomy and adjuvant radiation therapy than from radical prostatectomy alone for stages C2 and C3 disease or from radical prostatectomy alone or radiation therapy alone for stage D1a disease; however, the length of follow-up, number of patients treated, and problems in comparing our results with those from historical controls do not allow us to draw firm conclusions about the benefits of this combined therapy. Controlled, randomized studies clearly are required. The serum levels of prostate-specific antigen, but not prostatic acid phosphatase, were invariably elevated in patients at the time of clinical detection of disease recurrence and predicted recurrence up to 4 years before the event.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Neoplasm

Circadian-based infusional chrono-chemotherapy controls progressive metastatic renal cell carcinoma.

We treated 25 patients with progressive metastatic renal cell carcinoma with continuous infusion of 5-fluoro-2-deoxyuridine (FUDR) by implanted pump. FUDR was infused for 14 days at monthly intervals. Starting dose was 0.15 mg/kg/day intravenous or 0.25 mg/kg/day intra-arterial; intravenous doses were increased or decreased in increments of 0.025 mg/kg/day as permitted by toxicity. Circadian time modification of the infusion shape (sinusoidal with the peak centered around 6 p.m.) significantly lowered serious intravenous infusion-associated toxicity, allowing higher dose intensity. In 24 evaluable patients, two complete responses (8%), six partial responses (25%), and one minor response were seen. One secondary partial response was observed after infusional velban (total objective response rate 37.5%). Previously progressive disease was controlled in greater than 80% of our patients. During a median follow-up period of 8 months (range of 2-26 months), the overall survival for all 25 patients is 75%. Our results indicate that metastatic renal cell cancer responds to infusional chemotherapy and that the circadian shape of infusion markedly affects our ability to deliver effective doses.

Adult

Primary adenocarcinoma of urinary bladder. Clinicopathologic study of 16 cases.

The clinicopathologic and immunohistochemical features of 16 pure adenocarcinomas primary in the urinary bladder were reviewed. Only 3 patients were found to have disease confined to the urinary bladder. Of 13 cases with follow-up only 3 are free of disease. Histologically, the tumors were classified as signet ring cell (3), colloid (3), colonic type (5), clear cell (1), and not otherwise specified (NOS, 4). Immunohistochemically, all tumors but one colloid carcinoma were immunoreactive for cytokeratin and epithelial membrane antigen, and most tumors were likewise immunoreactive for carcinoembryonic antigen. Eight cases were immunoreactive for Leu M1 antigen. Prostate specific antigen, S-100 protein, and placental alkaline phosphatase were uniformly negative. No correlation between immunohistochemical profile and histologic type or clinical outcome was found. The utility of immunohistochemistry and other pathologic findings is reviewed.

Adenocarcinoma

Bladder replacement after cystoprostatectomy: efforts to achieve total continence.

Total bladder replacement with tubular sigmoid colon and detubularized ileocecal bowel segments was performed on 17 patients after cystoprostatectomy for bladder cancer. There were few complications and patient acceptance was excellent. Daytime continence was achieved in most patients but voiding patterns were superior with detubularized segments. However, enuresis was common with both segment types. Total urinary continence (day and nighttime continence) was achieved in 7 patients with an artificial urinary sphincter that was activated only at night. Total bladder replacement is an acceptable form of urinary diversion after cystoprostatectomy in appropriate patients.

Aged