Adequacy of chemotherapy prior to cytoreductive surgery in testicular carcinoma.

Removal of residual masses after cisplatin-based chemotherapy (cytoreductive surgery) for inoperable or metastatic testicular carcinoma has demonstrated that many partial regressions are defects without malignant cells. Such negative results allow a clarification of complete regression. Failure to achieve complete regression requires intensive salvage chemotherapy or bone marrow transplant. Extended initial chemotherapy could reduce these failures. Cytoreductive surgery was performed on 44 patients with inoperable stage II or stage III testicular cancer with residual defects following chemotherapy. The patients were evaluated according to whether (a) adequate treatment was given based on attaining normal markers followed by two additional courses of therapy, (b) normal markers were achieved but two additional courses were not administered, or (c) normal markers were never attained. These were subdivided into those receiving five or more courses of chemotherapy or fewer than five courses. Patients receiving two additional courses of chemotherapy after markers became normal had a low death rate (15.4%) and highest median follow-up. Fewer patients died if they had five or more courses of chemotherapy (11.8%). Of all those who attained normal markers with at least five or more courses of therapy, 10% are dead. The presence of residual malignant cells in those receiving five or more courses of therapy was 18.2% in contrast to 50% in those receiving fewer courses. Adequate chemotherapy and attainment of normal markers followed by two more courses of therapy results in fewer patients with residual malignant cells, a greater potential of cure, and less need for intensive salvage regimens.

Optimal number of chemotherapy courses in advanced nonseminomatous testicular carcinoma.

BACKGROUND: Nonseminomatous germ cell tumors (NSGCT) (testicular carcinoma) are a curable disease. Stages I and II are nearly 100% curable. Stage III has had remarkable progress in attaining complete regression, but a substantial number fail to be cured. Using platinum-based regimens such as vinblastine, bleomycin, and cisplatin (VBP), or using etoposide instead of vinblastine (BEP), or without bleomycin (EP), four courses of chemotherapy have become a national standard. Based on our prior experience with mithramycin (plicamycin), which used six courses, six courses of VBP chemotherapy were utilized as our treatment goal. This report challenges the concept that "standard therapy" for stage III testicular carcinoma is four courses. METHOD: From 1976 to 1990, 74 patients with advanced NSGCT were treated with standard doses of plantinum-based chemotherapies. Five or more courses were delivered to 41 patients and fewer than five courses to 33 patients. The intent of therapy was to attain as close to six courses as possible. Because of physician preference, patient adherence, or toxicity, some patients did not reach that goal. RESULTS: Of 33 patients receiving less than five courses, there were 28 (85%) complete responders, and 26 (78.8%) are alive. Of 41 patients receiving five or more courses, 38 (92.7%) had complete responses, and 34 (83%) are alive. One person in each group is living with nonresectable teratoma present. In the group receiving 5+ courses, two died from causes unrelated to testis cancer and had no testis cancer present. As a result of the initial treatment, there was no evidence of cancer in 24 (72.8%) in the group receiving less than five courses and 35 (85.4%) had no cancer after five or more courses. In considering only patients with advanced level of stage III disease in contrast to minimal or moderate stage III disease, there were fewer complete regressions with less than five courses (64.3%) than with five or more courses (88.0%). CONCLUSIONS: For minimal stage III disease, four courses of chemotherapy may be adequate. For advanced stage III disease, more chemotherapy provides fewer treatment failures. Once a complete response is achieved without restriction to an arbitrary number of courses, two additional courses may constitute a more curative regimen.

Association of immunohistochemical staining for p53 with metastatic progression and poor survival in patients with renal cell carcinoma.

BACKGROUND: Mutations of the p53 gene have been found in many types of human tumors. In some tumors, p53 gene mutations are associated with advanced disease and poor prognosis. There is wide variation in the reported incidence of p53 mutation in renal cell carcinoma, and its prognostic significance for this tumor is unknown. PURPOSE: This retrospective immunohistochemical study was designed to examine associations between p53 immunostaining and histologic type, tumor grade, clinical behavior, and survival. METHODS: Paraffin-embedded nephrectomy specimens collected from 1978 through 1986 from 175 patients were immunostained for p53 using the D07 monoclonal antibody. Positive staining for p53 has been linked to the accumulation of mutant p53 protein. Thirteen specimens of concurrent metastatic lesions were available from 11 primary cases. Clinical follow-up information was available on 164 patients. RESULTS: Immunostaining for p53 suggested the presence of p53 mutation in 49 (28%) of 175 renal tumors studied. Staining was associated with high tumor grade and stage but not with cell type or histologic pattern. Eleven (85%) of 13 metastatic lesions stained positively for p53, versus only four (36%) of the 11 paired primary tumors. Immunostaining for p53 was strongly associated with poor survival among patients without distant metastases at presentation. In this group, 10-year disease-specific survival was 78% for patients with nonstaining tumors versus 48% for those with p53-positive tumors (P < or = .003). There was an 87% 10-year disease-specific survival rate for patients with nonstaining Robson stage 1 tumors versus a 62% 10-year survival rate for patients with p53-positive Robson stage 1 tumors (P < .01). Multivariate analysis showed p53 immunoreactivity to be an independent predictor of survival for patients with nonmetastatic renal cell carcinoma, whereas tumor grade was not. CONCLUSIONS: Positive p53 immunostaining in renal cell carcinoma is associated with metastatic disease and poor survival in patients with early-stage disease. IMPLICATIONS: In renal cell carcinoma, mutations of the p53 gene may allow or contribute to the acquisition of metastatic potential.

Adjuvant chemotherapy for stage II nonseminomatous germ cell cancer of the testis.

BACKGROUND: The success of chemotherapy for Stage III testicular carcinoma warranted its use as an adjuvant therapy for Stage II cancer. The current report reflects the adjuvant program begun at the University of Minnesota using four courses of vinblastine, bleomycin, and cisplatin (VBP) before the onset of the Testicular Cancer Intergroup Study using two courses of chemotherapies. METHODS: A review of 78 patients with Stage II nonseminomatous germ cell tumors treated between 1972 and 1986 defined three groups: 19 patients treated between 1972 and 1979 with various adjuvant chemotherapies (termed "other"), 37 patients treated from 1975 to 1986 with VBP adjuvant chemotherapy, and 21 patients who received no therapy during the same era of VBP. The latter group was not offered adjuvant chemotherapy at other institutions or declined therapy. RESULTS: Nineteen patients received adjuvant chemotherapy before the cisplatin era. Their survival rate was 42%, including two patients treated with cisplatin-based chemotherapy for recurrence. In the group of 21 patients who did not receive adjuvant therapy, 14 (66.7%) survived. Of these, five had no recurrence and nine were treated for recurrence. In a third group, adjuvant VBP therapy was given to 37 patients, 32 of whom received four full courses. There have been no recurrences, and 36 (97.3%) remain alive; one obese patient with hypertension died of a ruptured aortic aneurysm 12.9 years after the retroperitoneal lymph node dissection. Nodal involvement was more extensive in the VBP group. CONCLUSION: Four courses of VBP adjuvant chemotherapy for pathologic Stage II testicular cancer resulted in a 100% cure rate, all patients having been followed up for more than 6 years. Whether two courses are as adequate remains to be determined when long-term follow-up is reported.

Computerized tomography in the diagnosis of appendicovesical fistula.

Appendicitis and its complications are among the causes of an enterovesical fistula, with approximately 100 such cases reported. This condition is seldom diagnosed preoperatively and surgery is often delayed. We report 2 cases of an appendicovesical fistula that were diagnosed preoperatively by computerized tomography (CT). We describe a CT finding consistent with the diagnosis, namely calcification in the thickened bladder wall adjacent to the cecum on noncontrast CT, which is a fecalith in the lumen of the fistula.

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.

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.

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.

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.

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.

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.

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.

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.

Malignant melanoma of the penis and male urethra: 4 case reports and literature review.

Malignant melanomas of the penis and male urethra are uncommon lesions. We report 3 new cases of male urethral melanoma and 1 case of penile melanoma, bringing the total numbers of reported cases to 26 and 57, respectively. The literature is reviewed, and biological, histopathological and therapeutic considerations are analyzed.

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.

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.

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)